The current status of hypothermia in cardiovascular surgery

T h e Cu

ent Status o f H y p o t h e r m i a in Car vascular S u r g e r y

By H E ~ Y

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term "hypodaermia" to signify the deliberate for t h e r a p e u t i c purposes. However, the to describe the state of a h o m e o t h e r m i c anhmaI w h e n its t e m p e r a t u r e is below normal for that individual. 2 H y p o t h e r m i a m u s t b e clearly d i s ~ n g u i s h e d from exposure to cold, although the relationslgp is complex, and exposure to cold is, in f a c t , a means of obtaining a lowered b o d y t e m p e r a t u r e . ~eVhen exposed to a cold environment, tile unanesthetJzed h o m e o t h e r m i c anhma] responds w i t h a n u m b e r of activities designed to conserve b o d y h e a t and increase its production, for example: consta'iction of peripheral vessels and shivering. Eventually, however, the animal becomes exhausted emd as h e a t loss exceeds heat production the b o d y t e m p e r a h l r e falls. On the other hand, the animal w h i c h is a d e q u a t e l y anesthet_ized does not r e s p o n d w i ~ such vigorous efforts to maintain its t e m p e r a tx~re, the metabolic and circulatory loads are minimized, and its b o d y t e m p e r a ture falls much earlier. Both animals b e c o m e hypothelnnie, b u t t h e physiologic changes to be observed in such different circumstances v a r y widely. In clinical h)~othemaia, the latter t y p e of experience is sought. N o t e r m i n o l o g y has y e t been a g r e e d upon to describe the various degrees of h y p o t h e ~ i a , b u t t h e following scheme is suggested and ~;~11 be used in this discussion: Moderate hypothermia . . . . . . . . . . . . . . . . . . . . 37'-28 C. Intermediate hypothermia . . . . . . . . . . . . . . . . . . 28-20 G. Deep hypoChe~ia . . . . . . . . . . . . . . . . . . . . . . . . 2 ~ 0 C. Supercooling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . below 0 C. withont ice formation. Freezing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . belowO C. with ice ~rormation. M o d e r a t e h y p o t h e ~ i a permits a reduction of metabolism b y a b o u t 50 p e r cent w i f l m u t the d a n g e r of ventricular fibrillation. If cooling is d e e p e n e d into tim "intennediat@" r a n g e there is a f u r t h e r reduefion in metabolism to a b o u t 25 p e r cent of normal b u t ventrieular fibrillation is almost certain to develop unless inhibited b y some specific means. W h e n deep h y p o t h e r m i a is o b t a i n e d in h o m e o t h e r m i c animals spontaneous r e w a r m i n g becomes impossible and cardiac activity ceases. T e m p e r a t u r e s below 0 C., with and w i t h o u t freezing, have been attained From the D e p a ~ m e n t of Surgery and the Hatsted Laboratorg for Experimental Surgerl¢, UntoerMtv of Colorado School of Medicine, Denver, Colo. The work reported [ r ~ th£~ laboratory has been .~lpported over the pa.et few years b~! grants [rorn the American Heart Asso~atton, U. S. Public llealth Service. m~d by eantracts wtth the S u r g e ~ Gev~.ral, U. S. Army. 228

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experflmel~tally3-r' b u t t h e r e is n o t a r e c o r d e d i n s t a n c e of a h u m a n r e c o v e r e d zffter b e i n g cooled to this d e g r e e . ItISTOmC~L ASVECTS E x p o s u r e to c o l d i n t h e f o r m o f c o l d w a t e r or ice has l o n g b e e n u s e d in m e d i c a l t h e r a p y . H i p p o c r a t e s U o b s e r v e d its a n a l g e s i c p r o p e r t i e s a n d r e c o m m e n d e d file a p p l i c a t i o n of cold w a t e r or ice for v a r i o u s i n j u r i e s , a p p a r e n t l y w i t h t h e o p i n i o n t h a t t h e cold w o u l d m i n i m i z e h e m o r r h a g e . I n R e n a i s s a n c e t i m e s f e v e r s w e r e t r e a t e d w i t h cold d r e n c h i n g a n d s o m e of t h e ! 7 t h C e n t u r y t e c h n i c s for c o l d h y d r o t h e r a p y o f t h e p y r e t i c p a t i e n t h a v e a r e s e m b l a n c e to c e r t a i n m e t h o d s u s e d in p r e s e n t d a y c h n cal p r a c t i c e for t h e i n d u c t i o n of h y p o t h e r m i a (fig. 1). I n 1797 R i c h a r d Sutton, Esq. of L i v e r p o o l w a s p r o b a b l y t h e first p a t i e n t to u n d e r g o t h e r a p e u t i c g e n e r a l h v p o t h e r m i a . H i s p h y s i c i a n , D r . J a m e . C u r n e , "i r e d u c e d his t e m p e r a t u r e to 83 F. b y k e e p i n g h i m in a salt w a t e r b a t h for a p e r i o d of 45 m i n u t e s . J o h n H u n t e r s a t t e m p t e d to f r e e z e a n d t h e n t h a w a c a r p b y s u r r o u n d i n g it w i t h m e l t e d s n o w . H e s a w t h e s l o w i n g d o w n of its a c t i v i t y a n d w a s a b l e to f r e e z e t h e fish a n d t h e n f l m w it out, b u t a l t h o u g h its l l e x i b i l i t y w a s restored, its l i f e w a s not. I n 1862 L~lalther, 9 w h i l e c o o l i n g r a b b i t s to 20 C., m a d e t h e i m p o r t a n t o b s e r v a t i o n t h a t artificial r e w a r r n i n g w a s n e c e s s a r y if recover), f r o m this t e m p e r a t u r e w a s to b e a c h i e v e d . T h e first m a j o r s t u d y o f t h e p o s s i b l e c l i n i c a l v a l u e of g e n e r M h y p o t h e r m i a w a s u n d e r t a k e n b y S m i t h a n d F a y I° in p a t i e n t s w i t h a d v a n c e d cancer. T h e y k e p t m o r e t h a n 100 p a t i e n t s m o d e r a t e l y h y p o t h e r m i c for u p to e i g h t days, a n d w e r e a b l e to d e m o n s t r a t e c o n c l u s i v e l y t h e t o l e r a n c e o f m a n to p r o l o n g e d t e m p e r a t u r e r e d u c t i o n to b e t w e e n 80 a n d 90 F. I n 1950, B i g e l o w , et el. 11 r e v i t a l i z e d this e n t i r e field of i n v e s t i g a t i o n b y d e m o n s t r a t i n g that dogs c o u l d t o l e r a t e t e m p e r a t u r e s of 20 to 25 C. w i t h c e s s a t i o n o f t h e c i r c u l a t i o n for 15 m i n u t e s . T h i s r e p o r t w a s a d i r e c t s t i m u l u s to t h e a d v a n c e m e n t o f o p e n - h e a r t s u r g e r y , a n d in 1953 L e w i s a n d T a u f i c '-~ re0orted the suture elosure of an interatfial septal defect using h y p o t h e r m i a a n d t h e c i r c u l a t o r y occlusion. A f e w m o n t h s later t h e first series of p a t i e n t s u n d e r g o i n g o p e n - h e a r t s u r g e r y for v a r i o u s c o n g e n i t a l d e f e c t s w a s r e p o r t e d b y S w a n et al. ~a Since t h e n the use of h y p o t h e r m i a a l o n e a n d m o r e r e c e n t l y t h e use of h y p o t h e r m i a c o m b i n e d w i t h e x t r a e o r p o r e a l c i r c u l a t i o n h a s r e s u l t e d in t h e d e v e l o p m e n t of t e c h n i q u e s to r e p a i r t h e m a j o r i t y of c o n g e n i t a l a n d a c q u i r e d c a r d i a c lesions. .

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A. T o l e r a n c e to C o l d

T h e t o l e r a n c e of d i f f e r e n t cells, tissues, a n d o r g a n i s m s varies w i d e l y . Poikilot h e r m i c a n i m a l s c a n w i t h s t a n d e x t r e m e t e m p e r a t u r e s a n d s o m e a r c t i c fishes m a i n t a i n n m ~ a l a c t i v i t y at t e m p e r a t u r e s a r o u n d 0 C. A m o n g s t h o m c o t l a e r m i e animals there are great differences between hibernators and non-hibernators. G o l d e n h a m s t e r s h a v e b e e n f r o z e n at --3 C. z a n d s i m i l a r e x p e r i m e n t s h a v e b e e n p e r f o r m e d w i t h n o n - h i b e r n a t i n g rats '4 w i t h e a r d f a c s t a n d s t i l l for 40

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Fig. 1 . - - T h e e a r l y days of surface cooling. m i n u t e s w i t h c o n s i s t e n t s u r v i v a l , a n d wSth s t a n d s t i l l f o r s e v e r a l h o u r s w i t h o c c a s i o n a l s u r v i v a l . C a t s s e l d o m s u r v i v e t e m p e r a t u r e s b e l o w 16 C., b u t S i m p s o n ~5 s h o w e d t h a t m o n k e y s c o u l d b e s u c c e s s f u l l y r e v i v e d f r o m 24 C. H o w e v e r , t h e store r e s u s c i t a t i o n o f n o n - h i b e r n a t o r s f r o m v e r y l o w t e m p e r a t u r e s d e p e n d s u p o n a n e s t h e s i a a t t h e o u t s e t , a r t i f i c i a l r e s p i r a t i o n as tile t e m p e r a t u r o d e c r e a s e s , a n d a s y s t e m o f r e w a r m i n g w h e n r e c o v e r y is d e s i r e d . R e m a r k a b l y l i t t l e is k n o w n a b o u t t h e t o l e r a n c e o f m a n t o e x t r e m e d e g r e e s o f c o l d . O b s e r v a t i o n s m a d e a l m o s t a c e n t u r y a g o 1~; in aP. i n s a n e asyh~m w h e r e s o m e o f t h e p a t i e n t s r a n n a k e d i n tile c o l d s h o w e d t h a t m a n c a n s u s t a i n a p p a r e n t l y n o r m a l a c t i v i t y w i t h a b o d y t e m p e r a t u r e o f o ~ . 7 - 2 9 . 5 C. D u r i n g

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~Zorld VVar I I, b r u t a l a n d i n c o n c l u s i v e e x p e r i m e n t s w e r e c a r r i e d o u t b y t h e G e n n a n s a t D a c h a u . ~r U n a n e s t h e t i z e d p r i s o n e r s w e r e c o o l e d in i c e - w a t e r a n d it was f o u n d t h a t t h e t e m p e r a t u r e a t w h i c h h a l f o f t h e m d i e d w a s 2"/ C, a n d t h e l o w e s t t e m p e r a t u r e r e c o r d e d w a s 26.7 C. D e a t h w a s t h o u g h t t o b e d u e t o v e n t r i c u l a r f i b r i l l a t i o n . L a u f m a n ~s p u b l i s h e d a f u l l y d o c u m e n t e d a n d d e t a i l e d a c c o u n t of s u r v i v a l f o l l o w i n g c o o l i n g to 18 C. ( r e c t a l ) in a n e g r o w o m a n . S h e s u b s e q u e n t l y lost b o t h legs a n d n i n e o f h e r f i n g e r s b u t h e r c e r e bral f u n c t i o n was u n i m p a i r e d a p a r t from a period of mnnesia.

B. Aletabolic Effects 1. Oxygen col~su~llption.~he m e t a b o l i c e f f e c t tff h y p o t h e ~ n ~ i a w h i c h sup e r c e d e s all o t h e r s b o t h i n m a g n i t u d e a n d i m p o r t a n c e is a r e d u e t i o l ~ i n o x y g e n c o n s u m p t i o n . N u m e r o u s s t u d i e s ~*''-'~-~-'~-'-'''-':~ h a v e all s h o w n t h a t as t h e t e m p e r a t u r e fails t h e o x y g e n c o n s u m l ~ t i o n d e c r e a s e s in a l i n e a r f a s h i o n . H o w e v e r , if s t ~ v e r i n g o c c m ' s d u r i n g t h e e a r l y s t a g e s t h e c o n s u m p t i o n of o x y g e n is temp o r a r i l y i n c r e a s e d . T h i s c a n b e a v o i d e d b y a d e q u a t e a n e s t h e s i a o r b y t h e use of m u s c l e r e l a x a n t s . G o r d o n e t alY e r e p o r t e d t h e o x y g e n c o n s u m p t i o n to b e r e d u c e d t o a b o u t 50 p e r c e n t o f tim p r e c o o l i n g l e v e l a t 30 C., to a b o u t 25 p e r c e n t a t 22 G., lO.9, p e r c e n t a t 16 C., 6 p e r c e n t a t 10 C., a n d 3 p e r c e n t a t 6 C. w i t h p e r v a s c u l a r c o o i n g . T h e flow rates were a p p r o x i m a t e l y 40-90 c e . / K g . / m i n , w i t h a m e a n of 60 ce./Kg./min. T h a t flow r a t e t r a d e r s u c h c i r c u m s t a n c e s is cme o f tire d e t e n n i n a n t s of o x y g e n e x t r a c t i o n a t l o w t e m p e r a t u r e s w a s c l e a r l y d e m o n s t r a t e d b y K a m e y a e t al. =a "~Vith h i g h ( 1 9 9 c e . / K g . / m i n . ) ttow r a t e s , O2 c o n s u m p ~ o n a t 20 C. w a s 2 . I ec./Kg./min., xvhile a t low flow r a t e s ( 4 0 c c . / K g . / r a i n . ) , i t w a s o n l y 1.1 ce. S i m i l a r l y at 10 C. t h e s e f i g u r e s w e r e 1.2 a n d .7 c e . / K g . / m i n , r e s p e c t i v e l y . In t h e s e d a t a : w i t h h i g h flow r a t e s o x y g e n c o n s u m p t i o n w a s r e d u c e d at 20 C. to 33 p e r c e n t a n d at 10 C. to 17 p e r c e n t o f n o r m a l , v a l u e s d e f i n i t e l y h i g h e r t h a n t h o s e o f G o r d o n . "-'~ I t is c l e a r i n e i t h e r case, t h a t a t 10 C. t h e r e r e m a i n s s i g n i f i c a n t o x y g e n c o n s u m p t i o n . C h a n g e s in t h e o x y g e n d i s s o c i a t i o n c u r v e a r e of c r i t i c a l i m p o r t a n c e in disc u s s i n g t h e l e v e l o f tissue o x y g e n a t i o n . B r o w n a n d I-Iill'-'I in 1923 s h o w e d t h a t c o o l i n g m o v e d t h e c u r v e u p w a r d a n d to t h e left. R o s e n h a i n a n d P e n r o d ez mad E d w a r d s e t alY ~; b e l i e v e d t h a t in s p i t e of this o x y g e n t r a n s f e r t o h y p o t h e r m i e tissues s i n c e A-V o x y g e n d i f f e r e n c e s r e m a i n e d c o n s t a n t . H e w e r r, a c o n s t a n t A-V oxygen difference does not p r o v e that tissue o x y g e n a t i o n was a d e q u a t e beexmse tire v e n o u s l e v e l m i g h t n o t h a v e b e e n d e t e r m i n e d b y t h e e x t r a c t i o n o f o x y g e n b y t h e t i s s u e s b u t r a t h e r b y t h e a d h e r a n c e o f o x y g e n to h e i n e - O n tile o t h e r h a n d , tile abili~7 o f o x y g e n to b e dissc)lved in t h e p l a s m a inc r e a s e s w i t h d i m i n i s h i n g t e m p e r a t u r e s a n d a t :20 C. t h e r e is a ,50 p e r c e n t m o~r e a~ S e in d i s s o l v e d oxygezl, a n d b e t w e e n 25 C. a n d 0 C. t h e a m o u n t o f o x y g e n d i s s o l v e d in t h e p l a s m a i n c r e a s e s f r o m 2.8 to ;t,9 v o l u m e s p e r c e n t . 27 A t v e r b, Iow t e m p e r a t u r e s t h e m n o u n t of o x y g e n d i s s o l v e d in t h e p l a s m a m a y b e s u m c i e n t for t h e m i n i m a l m e t a b o l i c d e m a n d s o f t h e t i s s u e s w i t h o u t iny o k i n g t h e u s u a l m e c h a n i s m s of o x y g e n r e l e a s e f r o m h e m o g l o b i n . T h i s m a y f u r t h e r e x p l a i u w h y c h a n g e s in flow r a t e , e v e n a t l o w t e m p e r a -

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t l o w t e m p e r a t u r e s ( 10 C , ) h i g h flow r a te s ( 6 0 ) m u s t b e m a i n t a i n e d if a d e q u a t e tissue o x y g e n a t i o n is to 2. A c i d b a s e bala~,~e.

T h e e s t i m a ~ o n of the d e g r e e a n d t y p e of acidosis pie. T h e s i m p l e m e a s u r e m e n t o f p l a s m a p i c t u r e of t h e a c i d b a s e b a l a n c e d u r i n g

t o correct t h e results. T h e

be ~ m o s t meaningless. B e c a u s e b o t h m e t a b o l i c a n d r e s p i r a t o r y factors p l a y a signif ic a nt p a r t in i n f l u e n c i n g t h e a c i d - b a s e b a l a n c e an e x a c t k n o w l e d g e of t h e sta te of respira-

CO2 is d i s s o l v e d in t i l e p l a s m a at l o w e r t e m p e r a t u r e s a f f e c t i n g t h e p l a s m a p H , a l t h o u g h this c h a n g e is offset b y a d e c r e a s e d p e r i p h e r a l p r o d u c t i o n of CO2 a n d an i n c r e a s e d e ~ r y i n g c a p a c i t y of t h e blood for CO._, ( a s b i e m b o n a t e ) . In p a ~ e n t s a n d e x p e r i m e n t a l a n i m a l s it h a s b e e n f o u n d t h a t a m e t a b o l i c acidosis m a y d e v e l o p 3° e s p e c i a l l y in t h e r e w a r m i n g p e r i o d :n a n d a n " a c u t e acidoNc s y n d r o m e " at tbds t i m e h a s b e e n d e s c r i b e d . 3e In t h e c linical a p p l i c a t i o n of d e e p h y p o t h e r m i a , acidosis h a s not p r e s e n t e d a signhqcant p r o b l e m :~a w o r k 34 has s h o w n t h a t a sign i f i c a n t acidosis can coat :ures. T h i s aeidosis is p r o b a b l y m o r e m a r k e d wit,h c o r e - i n d u c e d h y p o t h e r m i a t h a n w i t h g e n e r a l h y p o t l n e n n i a . Tbds m a y b e d u e of t h e te~-nperature g r a d i e n t s w h i c h o c c u r b e t w e e n v a r i o u s tissues a n d o r g a n s a n d t h e b l o o d w i t h this W e of h y p o t h e r ~ n i a (fig. 2 ) . As a resuIt of t h e s e g r a d i e n t s c o n s i d e r a b l e m a s s e s of tissue, s u c h a s m u s c l e , m a y b e p e r f u s e d b y b l o o d w i t h a t e m p e r a t u r e 10 to 15 C. l o w e r t h a n ttiat of the tissue itself. T h u s an o r g a n a t ~ to 30 C. m a y b e p e r f u s e d b y b l o o d a t 10 to 15 C. a n d b e in t h e d i s a d v a n t a g e o u s s i t u a t i o n of n e e d i n g 40-50 p e r c e n t of its n o r m a l o x y g e n r e q u i r e m e n t y e t b e u n a b l e to e xtr a c t that o x y g e n f r o m t h e blood. It is not s u r p r i s i n g t h a t u n d e r t h e s e eireurnstances o r g a n s le sor t to a n a e r o b i c m e t a b o l i s m a n d a m e t a b o l i c aeidosis results. 3. F l u i d shi,fts. A consistent i n c r ~ : s e in h e m a t o c r i t d u r i n g h y p o t h e n n i a has b e e n n o t e d b y n u m e r o u s o b s e r v e r s 13.35-38 a n d this c h a n g e h a s b e e n acc e p t e d as a n i n d i c a t i o n of d i m i n u t i o n in p l a s m a v o l u m e d u r i n g the c o o l i n g phase. T h e d e c r e a s e in p l a s m a v o l u m e is u s u a l l y a r o u n d 10 pe r c e n t or less, a n d c h a n g e s in t h e p l a s m a specific g r a v i t y a n d p l a s m a p r o t e i n s c o m m e n s u r a t e w i t h t h e alterations in h e m a t o c r i t a n d p l a s m a voh, m e h a v e also b e e n observed. :As w i t h m a n y of the o t h e r p h y s i o l o g i c c h a n g e s i n d u c e d b y h y p o ~k

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F~g. 2 , ~ T e m p e r a t u r e g r a d i e n t s b e t w e e n arterial b l o o d a n d muscle. It can b e seen that muscle at 25 C. is b e i n g p e r f u s e d b y b l o o d at 10 C. t h e r m i a t h o s e in t h e p l a s m a v o l u m e r e v e r t t o n o r m a l w h e n t h e p a t i e n t is rewarmed. T h e c l i n i c a l u s e o f h y i ) o t h e r m i a d o e s n o t t h e r e f o r e t)y i t s e l f r e q u i r e a n y c h a n g e s in the usual m a n a g e m e n t of fluid balance, except t h a t the infusion e f g l u c o s e is p r o b a b l y d e s i r a b l e f o r o t h e r r e a s o n s . 4. E l e c t r o l y t e c h a n g e s . ..... C o n s i d e r a b l e d i s c u s s i o n o c c u r s i n t h e literat~zre c o n c e r n L n g t h e chzmges i n flee l e v e l s o f i n d i ~ i d u a ] e l e c t r o l y t e s d u r i n g h y p o thermia. The reasons for the discrepancies reported ~e not always clear but m a y w e l l b e r e l a t e d to t h e v a r y i n g c o o l i n g t e c h n i c s a n d t y ~ e s o f a n e s d l e s i a u s e d in t h e d i f f e r e n t s t u d i e s . S o d i u m l e v e l s in t h e p l a s m a d o n o t c h a n g e o r s h o w a s l i g h t d e c r e a s e . "~Vynn:~9 s h o w e d t h a t in t h e p r e s e n c e o f i n ~ a v e n o u s i n f u s i o n s of 5 p e r c e n t g l u c o s e a s i g n i f i c a n t d i l u t i o n o f t h e e x ~ a e e l l u l a r fluid m i g h t c a u s e hy-ponatremia, se t h e d e l a y in m e t a b o l i s m o f t h e g l u c o s e r e s u l t s i n a n o s m o t i c d i l u t i o n o f ene p l a s m a . T h e g r e a t e s t v a r i a t i o n s in f i n d i n g s h a v e c o n c e r n e d p o t ~ s i u m . S e v e r a l inv e s t i g a t o r s h a v e n o t e d mn e l e v a t i o n o f s e r u m p o t a s s i u m , 1I-'t°-4~ w h i l e o t h e r s n o t e d a fall i n t h e s e r u m p o t a s s i u m level, az'z~.'~c T h e r e s e e m s l i t t l e d o u b t t h a t t h e s e d i f f e r e n c e s o f o p i n i o n d o n o t reflect i n c o m p a t i b l e o b s e r v a t i o n s b u t r a t h e r o b s e r v a t i o n s m a d e u n d e r d i f f e r e n t c i r c u m s t a n c e s . S w a n et e l ) z s h o w e d t h a t s e r u m p o t a s s i u m levels varied with the p H a n d b i c a r b o n a t e a n d a reciprocal r e l a t i o n s h i p exists b e t w e e n t h e s e r u m p H a n d t h e p o t a s s i u m level, T h e a m o u n t o f s e r u m c a l c i u m i n c r e a s e s ~H:~ b o t h in t h e i o n i z e d a n d b o u n d

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fractions. T h e c a l c i u m - p o t a s s i u m ratio is e l e v a t e d , w h i c h m a y b e r e s p o n s i b l e for the p r o l o n g a t i o n of systole d e s c r i b e d b y H e g n a u e r a n d l ) ' A m a t o , u~ C h a n g e s in this ratio affect m y o c a r d i a l s t a b i l i t y ~md efficiency a n d the c a r d i a c restilts of c h a n g e s in p H m a y b e m e d i a t e d t h r o u g h a lte r a tions in serur:n p o t a s s i u m a n d t h e c a l c i u m - p o t a s s i u m ratio. Swan et al. ~3 n o t e d a s ~ g h t e l e v a t i o n in s e r u m c h l o r i d e as did F i s h e r et al. s8 I n c r e a s e d a m o u n t s of m a g n e s i u m h a v e b e e n r e p o r t e d b u t do n o t a p p e a r to b e c l i n i c a l l y significant. T h e e l e c t r o l y t e c h a n g e s r e v e r t s p o n t a n e o u s l y to n o r m a l w h e n the p a t i e n t is r e w a r m e d a n d w h e n e m c i e n t r e s p i r a t i o n ha s b e e n restored. T h e r e f o r e t h e y do n o t r e q u i r e a n y t h e r a p y p e r se b u t the ir t e m p o r a l ) , local effects, e s p e c i a l l y u p o n m y o c a r d i a l i r r i t a b i l i t y , m a y be of c o n s i d e r a b l e i m p o r t a n c e .

C. Circttlatory S y ~ e m T h e c h a n g e s in c i r c u l a t i o n are, in t h e m a i n , p r o p o r t i o n a l to the o v e r a l l c h a n g e s in m e t a b o l i s m . T h e c a r d i a c o u t p u t is r e d u c e d a n d t h e r e is a fail in t h e p u l s e r a t e a n d arterial pressure. H a m i l t o n et al. "~4 w e r e a m o n g th e t3rst to r e c o r d t h e s l o w i n g of t h e p u l s e r a t e in cats d u r i n g i n d u c e d h y p o t h e r m i a . At 17 C. t h e c a r d i a c o u t p u t in dogs is r e d u c e d to 26 m l . / K g . / m i n , f r om 1 Io.o m l . / K g . / m i n , at 37 C. "2/ A t the s a m e t i m e t h e b l o o d p r e s s u r e falls from 126 m m . / H g to 54 m m . / H g a n d t h e p u l s e r a t e is r e d u c e d f r o m 170 to 26 p e r m i n u t e . H o w e v e r , if s h i v e r i n g is p e r m i t t e d w h i l e c o o l i n g is b e i n g i n d u c e d , t h e r e is a rise in c a r d i a c o u t p u t a n d a r t e r i a i pressure. H y p e r t e n s i o n ~nav. also b e n o t e d d u r i n g h y p o t h e r m i a i m m e d i a t e l y follov,-ing t h e r e l e a s e of cireula~tor~, occlusion. 4n V e n o u s p r e s s u r e m a y rise d u r i n g t h e p e r i o d of cooling, a n d a l w a y s does so d u r i n g a p e r i o d of c i r c u l a t o r y occlusion. T h e i n c r e a s e in p r e s s u r e d u r i n ~ t h e c o o l i n g p e r iod m a y b e d u e to p o s i t i v e p r e s s u r e r e s p i r a t i o n ; t h e e l e v a t i o n during t h e p e r i o d of circulatol T occlusion m a y b e d u e to i n c r e a s e d v e n o u s t o n e l i m i t i n g a n i n c r e a s e in c a p a c i t y of t h e v e n o u s reservoir. T h e total p e r i p h e r a l r e s i s t a n c e i n c r e a s e s a n d this is p r o b a b l y d u e to a s i m u l t a n e o u s i n c r e a s e in -,dscosity of t h e b l o o d t o g e t h e r w i t h an i n c r e a s e in v a s c u l a r tone. D i r e c t o b s e r v a t i o n of the c a p i l l a r i e s a~ h a s s u g g e s t e d thai inc r e a s e d viscosib-, w i t h a g g r e g a t i o n of r e d cells m a y b e t h e m o r e i m p o r t a n t factor. G e l i n a7 c o n s i d e r e d that the use of l o w m o l e c u l a r w e i g h t defftran as a d i l u t i n g i n f u s i o n m i g h t f a v o r a b l y d e c r e a s e t h e viscosity" a n d s h o w e d experim e n t a l l y t h a t this d i m i n i s h e d t h e a m o u n t of r e d cell a g g r e g a t i o n . C l i n i c a l c o n f i r m a t i o n of this c o n c e p t has b e e n o b t a i n e d b y L o n g 's a n d his associates w h o o b s e r v e d t h e c o n j u n c t i v a l c a p i l l a r i e s d u r i n g o p e r a t i o n a n d s a w a favor£ b l e d e c r e a s e in s l u d g i n g a f t e r t h e u s e of low m o l e c u l a r w e i g h t d e x t r a n . I n spite of t h e s e factors, d u r i n g short p e r i o d s of h y p o t h e r m i a , c i r c u l a t i o n a p p e a r s to b e a d e q u a t e to all p a r t s of t h e b o d y . T h e effects of h y p o t h e r m i a on t h e h e a r t are of vital i m p o r t a n c e . C a r d i a c w o r k is r e d u c e d . In vitro e x p e r i m e n t s s h o w t h a t the o x y g e n c o n s u m p t i o n o f isolated m u s c l e slices is r e d u c e d in a l i n e a r f a shion, +" a n d in vivo o b s e r v a t i o n s l m v e s h o w n t h a t t h e h e a r t r e m a i n s c a p a b l e of e x t r a c t i n g a d e q u a t e a m o u n t s of o x y g e n for its n e e d s e v e n at l o w t e m p e r a t u r e s . '~ C o r o n a r y flow is r e d u c e d n°

C U I l B E N T S T A ' I ' U S O l ,~ I t Y P O T I I E I I ~ ' I I A

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b u t this r e d u c t i o n is n o t p r o p o r t i o n a t e l y as g r e a t as t h a t in t h e s y s t e m i c circulation. M y o c a r d i a l f u n c t i o n as j u d g e d b y p r e s s u r e c o n t o u r t r a c i n g s ~ r e m a i n s a d e q u a t e a l t h o u g h t h e r e is a m a r k e d p r o l o n g a t i o n of s y s t o l i c c o n t r a c t i o n a n d i s o m e t x i e r e l a x a t i o n . "~5,5~ A t t e m p t s to i n c r e a s e t h e h e a r t r a t e a r t i f i c i a l l y u n d e r t h e s e c i r c u m s t a n c e s of r e d u c e d d i a s t o l e r e s u l t in c a r d i a c f a i l u r e . \~zitln p r o g r e s s i v e cooling, t h e e l e c t r o c a r d i o g r a p h i c c h a n g e s - c o n s i s t s e q u e n tially of bradycardia, prolongation of the P-II interval and QItS complexes, c h a n g e s in t h e S T s e g m e n t s a n d T w a v e s , p r e m a t u r e c o n t r a c t i o n s , v e n t r i c u l a r fibrillation, a n d finally c a r d i a c s t a n d s t i l l . Osborn in 1953 d e s c r i b e d s o m e c h a r a c t e r i s t i c c h a n g e s i n t h e S T s e g m e n t s , as a " c u r r e n t of i n j u r y " to w h i c h h e a t t a c h e d s e r i o u s p r o g n o s t i c s i g n i f i c a n c e as a p r e ~ n o n i t o r y s i g n of v e n t r i c u I a r fibrillation. H o w e v e r , E m s l i e - S m i t h "~' l a t e r s h e w e d t h a t t h e s e c h a n g e s a r e c o n s t a n t l y f o u n d in all c a s e s o f h y p o t h e r m i a a n d a r e n o t n e c e s s a r i l y of s e r i o u s O n e of t h e m a i n h a z a r d s in t h e u s e of h y p o t i m r m i a is v e n t r i c u l a r f i b n l l a t l o n . N o t o n l y is its i n c i d e n c e g r e a t e r u n d e r h y p o t h e r m i a t h a n n o r m o t h e i m i a b u t it is m e r e r e s i s t a n t to c o n v e r s i o n to n o r m a l r h y t h m , r''~ Tile precipitating factors and possible underlying causes are numerous. Cohl.--It is n a t u r a l to c o n s i d e r t h e r e d u c t i o n in t e m p e r a t u r e p e r se as a p o s s i b l e c a u s e , b u t in t h e a n a l y s i s of this f a c t o r a d i s g n c t i o n m u s t b e dr~awn b e t w e e n m y o c a r d i a l e x c i t a b i l i t y a n d i r r i t a b i l i t y . H e g n a u e r a n d A n g e l a k o s r'~ s h o w e d t h a t a r e d u e t i e n in t e m p e r a t u r e d e c r e a s e s c a r d i a c e x c i t a b i l i t y b u t a l s o l o w e r s t h e fibrillation t h r e s h o l d a n d i n c r e a s e s em-diac i r r i t a b i l i t y . T h i s f i n d i n g c e r t a i n l y m a k e s m o r e c o m p r e h e n s i b l e t h e o b s e r v a t i o n s of n u m e r o u s o t h e r i n v e s t i g a t o r s t h a t a g r e a t v a r i e t y of s t i m u l i c a n i n d u c e f i b r i l l a t i o n d u r i n g hypothermia. B o t h e x p e r i m e n t a l a n d clinical e x p e r i e n c e h a s s h o w n t h a t v e n t r i e u l a r fibrillation is less likely to o c c u r w h e n t h e t e m p e r a t u r e is k e p t a b o v e 28 C. Hypoxia.-During p e r i o d s o f v e n o u s i n f l o w o c c l u s i o n w i t h s i m u l t a n e o u s c l a m p i n g o f t h e a o r t a m y o c a r d i a l h y p o x i a d e v e l o p s a n d if t h e o e e ! n s i o n is p r o l o n g e d b e y o n d 6 m i n u t e s t h e i n c i d e n c e o f fibrillation i n c r e a s e s . :'7.r's Electrolyte Changes.-:gacal d m n g e s in m y o e a r d i a I e l e c t r o l y t e levels m a y b e s i g n i f i c a n t , p a r t i c u l a r l y a l t e r a t i o n s in p o t a s s i u m a n d c a l c i u m . M o n t g o m e r y e t al. r'~ felt t h a t t h e r e w a s a s h i f t of p o t a s s i u m i n t o t h e m y o c a r d i a l cell d u r i n g t h e p r e f i b r i l l a t o r y s t a g e in a n i m a l s t h a t w e r e a c i d o t i c . T h i s w a s c o n s i d e r e d to b e a n i m p o r t a n t p r e c i p i t a t i n g f a c t o r in t h e o n s e t o f fibrillation. T h i s c o n c e p tion h a s s i n c e b e e n d e n i e d b y C o v i n o e t al. e'° w h o f o u n d t h a t p o t a s s i u m l e f t t h e cell, T h e p r e c i s e level o f i n t r a e e l l u l a r p o t a s s i u m m a y n o t h e as i m p o r t a n t as t h e c a l c i u m - p o t a s s i u m r a t i o " ' a n d s i n c e s e v e r a l o b s e r v e r s h a v e n o t e d e l e v a tions in c a l c i u m d u r i n g h y p o t h e r m i a , a l t e r a t i o n s in this r a t i o a r e likely. pH.~The a c i d o s i s w h i c h o c c u r s d u r i n g h y p o t h e r m i a is p r o b a b l y i m p o r t a n t as ~m i n i t i a t i n g or p r e c i p i t a t i n g f a c t o r a~=.~' a n d its a v o i d a n c e b y h y p e r v e n t i l a tion r e d u c e s t h e i n c k l e n c e o f fibrilhltion. '~' l l o w e v e r , N i a z i a n d L e w i s a2 b e lieve t h a t t h e i n t e n t i o n a l u s e o f h i g h c o n c e n t r a t i o n s of C O e in t h e r e s p i r a t o r y g a s m i x t u r e s p r e v e n t s t h e d e v e l o p m e n t of fibrillation. T h i s a p p a r e n t p a r a d o x is p r o b a b l y h e c a u s e n e i t h e r h i g h n o r l o w p l l ' s b y t h e m s e l v e s affect t h e in-

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e i d e n c e o f fibrillation, b u t t h e m a i n t e n a n c e of a s t e a d y p H w i t h o u t s u d d e n c h a n g e s d , ~ i n g c o o l i n g o r r e w o x m i n g is t h e m o s t i m p o r t a n t f e a t u r e to . b e attained. However, increasing pCOz moves the oxyhemoglobin dissociation c u r v e t o t h e r i g h t a n d d o w n w a r ~ f l a e r e b y i n c r e a s i n g t h e e ~ c i e n ~ y of o x y g e n e x t r a c t i o n f r o m t h e b l o o d w h i c h m a y b e i m p o r t a n t in p r e v e n t i n g m y o c a r d i a l h y p o x i a a n d s u b s e q u e n t fibrillation. Venous P r e s s u r e . ...... B i g e l o w ~1 w a s u n a b l e to p r e v e n t o r t r e a t v e n ~ ' i e u l a r fibrillation b y a n y elec~'ical or m e c h a n i c a l m e a n s except b y r e d u c i n g the i n f l o w p r e s s u r e w h i c h b u i l d s u p d u r i n g tile p e r i o d o f c i r c u l a t o r y o c c l u s i o n . Autonomic Nervous System. Montgomery et al. "~9 d e m o n s t r a t e d t h a t vent r i e u l a r f i b r i l l a t i o n c o u l d b e p r e v e n t e d b y t h e i n t r a c o r o n a r y i n j e c t i o n of n e o s t i g m i n e , a n a n t i c h o l i n e s t e r a s e a g e n t . S t i m u l a t i o n o f t h e p e r i p h e r a l e n d of t h e e t al. ~a a n d N a v r a t i V 4 , a p a t h e t i c i m p u l s e s inh i b i t e d t h e d e v e l o p m e n t o f v e n t r i c u l a r fibrillation. ~ # e c h a n i e a l S t i m u l L .......H e ~ a u e r e t al. "'~ s h o w e d t h a t t h e m e r e p r e s e n c e of a n i n t r a v e n t r i e u l a r c a t h e t e r i n c r e a s e d t h e l i k e l i h o o d o f fibrillation, a n d c o u n t less o b s e r v a t i o n s a t t h e o p e r a t i n g t a b l e h a v e c o n f i r m e d t h a t m e c h a n i c a l s t i m u l i o f a n y s o r t m a y s e t off v e n t r i c u l a r f i b r i l l a t i o n in a n i r r i t a b l e h e a r t . E p i n e ~ g h r i n e . .......D u r i n g h ~ o t h e r m i a increased amounts of epinephrine and n o r e p i n e p h r i n e c i r c u l a t e in t h e b l o o d . ¢~ S i n c e B e r n e in I9545° h a d s h o w n Lhat i n j e c t e d e p i n e p h r i n e m a y s t i m u l a t e fine o n s e t o f v e n t r i c u l a x fibrillation this i n c r e a s e d level o f e n d o g e n o u s c a t a c h o l a m i n e s m a y b e i m p o r t a n t . A n e ~ h c 4 i c s . . ....... C y c l o p r o p a n e ~ h a s b e e n i n c r i m i n a t e d as a n i n f l u e n c e m t h e p r o d u ~ i o n o f fibrillation e s p e c i a l l y w h e n c o m b i n e d w i t h e p i n e p h r i n e . P e n toGha] is t h o u g h t less l i k e l y t o p r o d u c e f i b r i l l a t i o n t h a n N e m b u t a l , b u t m o s t o f t h e a n ~ t h e t i e f a c t o r s c o n i : e r n e d wiCn ~ e d e v e l o p m e n t o f f i b ~ t l a t i o n e r e v e n t i l a t o r ) , r a t h e r t h a n phea-macologie. J

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antifibrillatomf d r u g s h a v e b e e n r e c o m m e n d e d . Neos t i g r n i n e w a s first s u g g e s t e d b y M o n t g o m e r y . r'9 O n e t o t w o co. o f a l : 4 f f 0 0 s o l u t i o n is in~ected i n t o t h e r o o t o f tlne c r o s s - d a m p e d a o r t a to p e r f u s e t h e c o r o n a r y a r t e r i e s . T h i s bofla s l o w s t h e h e a r t d u r i n g t h e p e r i o d o f o c c l u s i o n road p r o t e c t s a g a i n s t fibrillation. T h e u s e o f q u i n i d i n e w a s r e p o r t e d " b y t3ol1,-m,es B e r m a n et al. 6 9 A n g e l a k o s 7 0 a n d J o h n s o n e t al. 71 A n t i h i s t a m i n e s , l o c a l a n e s t h e t i c s a n d t r a n q m h z e r s h a e all b e e n t e s t e d b u t none has attained general clinical acceptmaee. B o t h h y p e r v e n t i l a t i o n 6x a n d t h e u s e o f h i g h c o n c e n t r a t i o n s of C O 2 in t h e r e s p i r a t o r y g a s mixt~are re ha-we b e e n a d v i s e d a n d t h e r a t i o n a l e o f t h o s e m e t h o d s has been discussed above. They are both effective. I n t r a v e n o u s n u t r i e n t s o l u t i o n s s u c h as d e x t r o s e , g l y e i n e , d e x t r a n , a n d f a t e m u l s i o n s h a v e b e e n s h o w n b y C a r a n n a e t a]. 7a to d e c r e a s e t h e i n c i d e n c e o f f i b r i l l a t i o n in d o g s c o o l e d to C. a n d s u b j e c t e d to c a r d i a c incision. N o t o n l y w a s t h e i n d d e n e e o f f i b r i l l a t i o n less in t h e s e a n i m a l s b u t w h e n it occ u r r e d resuscitation w a s easier. P e r f u s i o n of t h e c o r o n a r y a r t e r i e s d u r i n g t h e p e r i o d o f c i r c u l a t o r y o c e l u Prevention.-Many

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sion h a s b e e n a d v i s e d b y S h u r n w a y et al. TM a n d E d w a r d s e t al. '-'6 I n f i l t r a t i o n of t h e a ~ i u m a n d t h e S-A n o d e w i t h " p r o c a i n e h a s b e e n ~ i e d b u t a g a i n this m e t h o d h a s n o t b e c o m e g e n e r a l l y a c c e p t e d . 7s D. C e n t r a l N e r v o u s S y s t e m

The important questions concerning the relationship between hypothermia a n d t h e c e n t r a l n e r v o u s s y s t e m a r e t h e s e : ( 1 ) w h a t is t h e l o w e s t t e m p e r a t u r e w h i c h c a n b e t o l e r a t e d ? ( 2 ) W h a t is t h e e f f e c t o f h y p o t h e r m i a on c e r e b r a l , c o r d , a n d n e r v e f u n c t i o n ? a n d ( 3 ) h o w l o n g will t h e c o r d a n d b r a i n t o l e r a t e c o m p l e t e c e s s a t i o n of c i r c u l a t i o n a t v a r i o u s t e m p e r a t u r e s ? T h e d a t a c o n c e r n m g t h e p a t h o l o g y o f c o l d in t h e c e n t r a l n e r v o u s s y s t e m , a r e conflicting. P a r k i n s e t al. 76 f o u n d s e r i o u s b r a i n d a m a g e w i t h d i f f e r e n t i a l c o l d p e r f u s i o n w h e n t h e b r a i n t e m p e r a t u r e s of d o g s w e r e l o w e r e d b e l o w 14 C. O n t h e o t h e r h a n d , A d a m s a n d P e v e h o u s e 77 a c h i e v e d s u r v i v a l w i t h o u t n e u r o l o g i e d a m a g e in d o g s c o o l e d to ] 2 C. b r a i n t e m p e r a t u r e b y r e g i o n a l p e r f u s i o n . N i a z i a n d L e w i s rs c o o l e d d o g s b y i m m e r s i o n to 7 C. w i t h r e c o v e r y w i t h o u t b r a i n d a m a g e , a n d m o r e r e c e n t l y , G o r d o n a n d J o n e s et al. -02 u s i n g p e r v a s c u l a r c o o l i n g a c h i e v e d c e r e b r a l t e m p e r a t u r e s of 8 - 1 2 C . w i t h o u t d a m a g e . I t a p p e a r s , t h e r e f o r e , t h a t c o o l i n g to t e m p e r a t a ~ r e s ,as l o w as 8 C. b y this t e c h n i c , d o e s n o t r e s u l t m p a t h o l o g y in d o g s . As r e g a r d s m a n , c e r t a i n p a t i e n t s in T e m p l e F a y ' s series ~° w h o s u c c u m b e d h a d b e e n s u b j e c t e d to t e m p e r a t u r e s d o w n to 25 C. f o r as l o n g as 150 h o u r s . A s t u d y of t h e s e b r a i n s b y S a n o a n d S m i t h 7~ d i d n o t r e v e a l a n y p a t h o l o g y . P e r i p h e r a l n e u r o l o g i c a l lesions h a v e b e e n o b s e r v e d in b o t h a n i m a l s a n d h u m a n s ,:ooled b y i c e - w a t e r i m m e r s i o n s° w h e n e x p o s u r e to t h e i c e - w a t e r w a s p r o l o n g e d . In t h r e e c a s e s m e a s u r e d , t h e t e m p e r a t u r e o f t h e e x t e n s o r m u s c l e m a s s o f t h e f o r e a r m fell to 3 - 5 C. T h i s c o n f i r m s t h e e x p e r i m e n t a l w o r k of D e n n y - B r o w n et aI., s'-' w h o d e m o n s t r a t e d p e r i p h e r a l n e r v e l e s i o n s b e l o w 8 C. R e c e n t clinical e x p e r i e n c e s w i t h p r o f o u n d h3q~othemqia h a v e r e v e a l e d t h e p o s s i b i l i t y o f s e v e r e c e r e b r a l d a m a g e a r i s i n g s o m e da_ys o r e v e n w e e k s a f t e r t h e p a t i e n t h a s b e e n c o o l e d , s1 T h e s y n d r o m e p r o d u c e d "~v t h e s e c h a n g e s c o n sist o f Pm~kinsonism a n d p r o g r e s s i v e c e r e b r a l d e t e r i o r a t i o n to t h e t i m e o f d e a t h . I t is t h o u g h t t h a t m i c r o s c o p i c a g g r e g a t i o n s o f r e d cells a n d w h i t e cells fin t h e c e r e b r a l c a p i l l a r i e s r e s u l t in m i c r o - i n f a r c t s , a n d t h e s e lesions s e e m to b e m o r e c o m m o n in d l i l d r e n t h a n in a d u l t s . F o r this r e a s o n B j o r k s~ a d v i s e s a g a i n s t tim u s e o f this t e c h n i c in c h i l d r e n . H y p o t h e r m i a laas a s i g n i f i c a n t d e p r e s s a n t a c t i o n on b r a i n a n d n e r v e f u n c tion, a n d b e c a u s e o f this d e p r e s s a n t a c t i o n , h y p o t h e r m i a is a n e f f e c t i v e m e t h o d of p r o d u c i n g a n e s t h e s i a , sa E l e c t r o e n c e p h a l o g r a p h y s h o w s t h a t v o l t a g e a m p l i t u d e b e g i n s to fall b e t w e e n 32-434 C . u n t i l t h e level o f e l e c t r i c a l s i l e n c e is r e a d m d a t 1 8 - 2 0 C . 84 B l a i r e t al, an in a s t u d y o f h u m a n s u n d e r g o i n g c a r d i a c s u r g e r y d u r i n g h y p o t h e r m i a , f o u n d t h a t t h e c a r d i o v a s c u l a r reflexes r e m a i n e d i n t a c t d o w n to a b o u t 0.27 C. H o w p r o t e c t i v e is h y p o f l m r m i a a g a i n s t t h e d a m a g e o f a n o x i a o r i s e h e m i a ? E v i d e n c e f r o m d o g s , R~ c a t b r a i n slices in v i t r o 8.~ a n d h u m a n s s7 c o n f i r m t h a t cerebral oxygen consumption decreases linearly with temperature. Lougheed a n d K a h n *a f o u n d t h a t a t 30 C,, t h e c e r e b r a l m e t a b o l i c r a t e of d o g s w a s r e -

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ducked to 5 0 o e r cent, a n d a t 2,5 C, to 2 5 p e r c e n t o f n o r m o t h e n n i c c o n t r o l . 5 m i n u t e c i r c u l a t o r y occluL o u g h e e d o r a l . ss o c c l u d e d p a t i e n t s for p e r i o d s u p to 140.5 m i n u i e s w i t h o u t 1 3 - 1 8 C, t o l e r a t e d 25-435 m i n u t e s o{ Cooled t o ~ 1 2 C. silniconsurnpti0n was studied t h a t e a d a 5 0 p e r c e n t red u c ~ 0 n in oXygen C0nSumpti0n d o u b l e s d~e Safe p e r i o d for c i r c u l a t o r y ~rest0

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T h a t t h e s e p e r i o d s o f c i r c u l a t o r y arrest a r e in f a c t r e a s o n a b l e was b o r n e out b y ex~ ental circul c c c l u s i c n s of o n e h o u r i n dogs at I 0 C. In patients a t s i m i l a r t e m p e r a t u r e s , o c e l u s i c n s of over one h o u r w e r e not f o l l o w e d ~ - e i t h e r e l e e ~ o e n c e p h a l o g r a p h i c or n e u r o l o g i c e v i d e n c e of c e n t r a l n e r v o u s T h e p r o t e c t i o n a f f o r d e d b y l a y p e t h e r m i a to t h e s p i n a l cord w h e n the t h n r a c i c aorta is , c l a m p e d has b e e n a m p l y d e m o n s t r a t e d b y Pontius et al. s9 O w e n s et a12° a n d ins e t M. 7e A tw o - to t h r e e - f o l d i n c r e a s e in t o l e r a b l e t~eriods of aortic-clamping d e m o n s t r a t e d at t e m p e r a tures in t h e r a n o_ liversit?¢ of C o l o r a d o h y p o t h e r m i a to 30 C. is r o u t i n e l y u s e d in all o p e r a t i o n s for c o a r c t a t i o n of the aorta.

t e e ~ v e effect w a s noted, a n d 3 ) t h e m o d e of action d i d not a p p e a r to b e b e c a u s e o f r e d u c t i o n in c~erebral e d e m a . C l i n i c a l l y , the u s e of h y p o t h e r m i a i n

a n d S p e n c e r 92 d e m o n s t r a t e d t h e a d v a n t a g e of c o o l i n g p a t i e n t s w h o do n o t i m m e d i a t e l y r e c o v e r n e u r o l o g i e f u n c t i o n f o l l o w i n g c a r d i a c arrest a n d rest~eitation. T h i s p r a c t i c e h a s n o w b e c o m e s t a n d a r d t r e a t m e n t u n d e r t h e s e c o n d i t i o n s.

E. Respiratory Syxtem H y p o t h e ~ i a d e p r e s s e s s p o n t a n e o u s r e s p l r a t on, a n d if t h e te mpe r a t~lr e is r e d u ~ d s u ~ c i e n d y a p n e a e n s u e . T h e exact p o i n t at w h i c h this occurs de-

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m e t a b o l i c reasons, assistance to the respiration d u r i n g t h e i n d u c t i o n of anesthesia is desirable. N o significant p a t h o l o g y of t h e lung has b e e n identified as b e i n g c a u s e d b y s h o r t t e r m h y p o t h e m n i a alone. F. E n d o c r i n e S y s t e m H y p o t h e ~ i a is a c c o m p a n i e d b y a m a r k e d d e p r e s s i o n of a d r e n a l cortical secret~ion in the d o g 2 z,~ T h e secretion of A C T H a n d t h e a b i l i t y of the cortex to r e s p o n d to e x o g e n o u s A C T H a r e b o t h diminished. Swan et al. 9'~ f o u n d that m a j o r o p e r a t i v e stress d i d not c a u s e e l e v a t i o n of p l a s m a steroids in h y p o t h e r m i c patients. Both c o n j u g a t i o n a n d excretion w e r e s i m u l t a n e o u s l y depressed, b u t , u p o n r e w a k i n g , adreno-cortJeal secretion w a s p r o m p t l y res u m e d at a level reflecting t h e m a g n i t u d e of t h e surgical t r a u m a . Thus. as r e g a r d s t h e b o d y r e s p o n s e to surgical t r a u m a inflicted d u r i n g the cold state, hypothermAa a p p e a r s m e r e l y to "stop the clock" temporaril),, a n d on r e w a r m ing t h e u s u a l r e s p o n s e s are o b t a i n e d . G. T h e K i d n e y M o s t observers 9c'9~ h a v e o b s e r v e d t h a t r e n a l b l o o d flow a n d g l o m e r u l a r filtration r a t e are d e p r e s s e d . T o t a l u r i n e v o l u m e r e m a i n s a l m o s t normal. ~ he a b i l i t y of t h e k i d n e y to p r o d u c e a m m o n i a or to acidify u r i n e d e c r e a s e s with t e m p e r a t u r e , b u t t h e s e f u n c t i o n s r e t u r n s l o w l y to n o r m a l in t h e '24 hours following rewarming. H y p o t h e r r n i a p r o t e c t s t h e k i d n e y f r o m i s c h e m i c d a m a g e a n d t h ¢ use of local h)q2othermia b y p a c k i n g t h e k i d n e y s with ice-bags results in a slgmfi .ant p r o l o n g a t i o n of t h e t i m e d u r i n g w h i c h a k i d n e y m a y b e totally i s c h e m i c a n d y e t r e c o v e r its n o d a l function. Nevertheless, p a t i e n t s u n d e r g o i n g resections of a o r ~ c a n e u r y s m s u n d e r h y p o t h e ~ i a s o m e t i m e s show a significant d e p r e s sion of r e n a l f u n c t i o n p o s t - o p e r a t i v e l y w h i c h m a y n e v e r r e t u r n to n o r m a l . H. T h e L i v e r H e p a t i c b l o o d flow is d i m i n i s h e d d u r i n g hy-pothermia b u t this does n o t s e e m to give rise t o s e q u e l a e unless t h e p e r i o d of h y p o t h e r m i a is p r o l o n g e d b e y o n d 6 h o u r s w h e n t h e r e is s o m e d e p l e t i o n of l i v e r g l y c o g e n . B e r n h a r d et al. 1°° s h o w e d t h a t dogs w e r e a b l e to s u r v i v e severe i s c h e m i a of t h e live1 ~ if t h e y w e r e h y p o t h e r m i e , a n d for this reason, d u r i n g h e p a t i c o p e r a t i o n s requixing p r o l o n g e d c l a m p i n g of t h e p o r t a l vein o r h e p a t i c a r t e r y hypot3a.~rmia transplantation wo~d maintain nodal of 2 ~ 2 2 C.

viability f o r 12 h o u r s at t e m p e r a t u r e s

I. T h e C l o t t i n g M izwn Studies of t h e c l o ~ n g me-~-mnism in t h e d o g b e a r so little r e l a t i o n t o t h e results o b t a i n e d f r o m h u m a n s t h a t t h e y w~dl n o t b e d i s c u s s e d here. B u n k e r a n d G o l d s t e i n 1°2 m e a s u r e d v a r i o u s d o t t i n g factors in 10 p a t i e n t s u n d e r g o i n g neurosurgieal proced~ a n d c o n c l u d e d t h a t w i t h t h e exception of a sig-

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niiqcant r e d u c t i o n m p r o t h r o m b i n c o n s u m p t i o n , t h e c h a n g e s in c o a g u l a t i o n seen w e r e s h n i l a r t o those observed during surgery and transfusions at normal temperatures. V o n K a u l l a a n d S w a n l°a in a n y b l e e d i n g t e n d e n c y d u e to g time nor in,ent. h e m o r r h a g e w a s o n e of t h e U n i v e r s i t y of C o l o r a d o s e r i ~ s as r e p o r t e d b y S w a n y of h y p e r c o a g u l a b i l i t y occuris t r u e , h y p e r c o a g u l a t i o n " or e p i s o d e s w h i c h is s e e n a f t e r vn. N o n e t h e l e s s , 4 o f ]Bunker ,e t h r o m b o s i s , a n d p u l m o n a r y artery and cerebral thrombosis during the postoperative period was a lethal c o m p l i c a t i o n in £our p a t i e n t s in t h e series o f 111 p a t i e n t s undex'Ko n g i n t r a c a r d i a c s u r g e D, b y S w a n a n d B l o u n t . a°4 F o r t h e s e r e a s o n s , f r e s h b l o o d is u s e d f o r t h e first t w o t r a n s f u s i o n s g i v e n

o p e r a t i v e l y b e c a u s e o f the t r e m e n d o u s size of t h e i r p u l m o n a r y v a s c u l a r t r e e a r e s t a r t e d o n h e p a r i n w h e n t h e c h e s t t u b e s c e a s e d r a i n i n g , mad a r e c o n t i n u e d on a n t i - c o a g u l a n t t h e r a p y f o r s e v e r a l w e e k s . IXlE~ODS

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Surface cooling has bec ~f m o d e r a t e h y p o h h e r m i a _ A s us, th~ foll o w i n g m e t h o d is u n i f o r m ;clew ~05 in T o r o n t o , B r o m l ° 6 in L e i d e n , Z i n d l e r I°7 in D u s s e l d o r f , a n d Scllick l°s in London 1. T h e r e c t a l t e m p e r a t u r e is r e d u c e d to 3 ( L ~ 2 C. T h i s is t h e l o w e s t level reached after drift, and every i n c l u d i n g t h e u s e o f d i a t h e r r o y , is m a d e to p r e v e n t t h e t e m p e r a t u r e f r o m f a l I i n g b e l o w 30 C . "~s 2. C o o l i n g is a c h i e v e d b y i m m e r s i o n in i c e w a t e r . T h e p a t i e n t , p r e m e d i e a t e d b y D e m e r o l m e o e r i d i n e ) or a b a r b i t a n d small doses of scopolamine ( not m o r p h i n e o r a t r o p i n e ) , is a n e s t h e t i z e d t o t h e s e c o n d s u r g i c a l p l a n e w i t h e t h e r . H e is t h e n i m m e r s e d in a Dab c o n t a i n i n g l u k e w a r r n w a t e r . W h e n all v~tal s i g n s a p p e a r s t a b l e , c u b e s o f ice ( a b o u t 50 to 75 ]bs, f o r a n a d u l t ) a r e a d d e d to t h e t u b . T h e w a t e r is c o n s t a n t l y s t i r r e d . A n a d u l t m a y t a k e 30 to 60 m i n u t e s , a n d a s m a l l c h i l d 8 t o 12 m i n u t e s to cool to 33 G. ( r e c t a l ) , a t w h i c h t e m p e r a t u r e h e is r e m o v e d to t h e o p e r a t i n g t a b l e . T h e e n d t e m p e r a t u r e w i t h b e a b o u t 3 0 30.5 C, w i t h t h i s m e t h o d , A f t e r r e m o v a l f r o m fl~e t u b t h e p a t i e n t ' s skin is c~zrefully d r i e d a n d p o w d e r e d a n d t h e d i a t h e r m y coil a t t a c h e d a r o u n d t h e

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4: D u r i n g t h e p r o c e d u r e , a c o n s t a n t d r i p o f 5 p e r c e n t d e x t r o s e is m a i n t a i n e d a t 3 0 to 4 0 d r i p s a m i n u t e . A d e l i b e r a t e h y p e r ~ b e n e f i c i a l e f f e c t o f i n ~ a v e n o u s n u t r i e n t s on th~ t h e ~ i a n o w a p p e a r s to b e c o n f i r m e d , r~

a r e c o n s i d e r e d to b e h e l p f u l in a v o i d i n g in hypothermia.~04 A l o w b l o o d v o l u m e is ~s p o o r l y t o l e r a t e d b y t h e h y p o t h e r m i e i n d i v i d u a l 2 °~ 6. T h e p a t i e n t is r e w a r m e d b y i t h e pelvis a n d h e m u s t b e b r e a t h i

sacral area. O t h e r a g e n t s b e s i d e s et] hyde, curare, and opiates t h e s t i m u l u s of cold. T h e

c h a m b e r s , u'~ T h e s e h a v e t h e d i s a d v a n t a g e o f t a k i n g l o n g e r t h a n i c e , w a t e r i m m e r s i o n . W a r m i n g m a y b e a s s i s t e d b y w a r m b l a n k e t s , l i n t w a t e r bottles, t e m p e r a t u r e - c o n t r o l b l a n k e t s , a n d w a r m x~;atcr i m m e r s i o n £~ wolf a~ di.~tlaermy An entirely different extracorporeaI technic was altan e o u s l y b y B o e r e m a et a12 ~ a n d Delorme.aa~: T h i s tile mrterial p r e s s u r e to p u s h t h e a n i m a l ' s h e p a r i n i z e d exc h a n g e r a n d r e i n f n s e it into a vein, a n d G o l l a n et al. alT a n d P i e r c e a n d P o f Icy, ~ su :iM c o o l i n g circuit. B r o cooling f through the heat exchanger. Dogliotti and Ciocatto' oo ieal application of the c o m b i n e d m e t h o d s of extracorporeal circulation and h y p o t h e r m i a a n d this t e c h n i c b y Y o u n g , et al. TM u s i n g t h e ir s y s t e m h a s b e e n u s e d s u c c e s s f u l l y f o r t h e i n d u c t i o n o f all d e g r e e s o f h y p o t h e r m i a . U r s e h e I e t a12 zx O s b o r n et al. xea a n d G e b a u e r r-'z c r e a t e d v e r y e f f e c t i v e h e a t e x c h a n g e r s o u t of t h e i r r o t a t i n g disc o x y g e n a t o r s , t h u s n o t r e q u i r i n g a n a d d i t i o n a l c o o l i n g u n i t in t h e circuit. M o s t r e c e n t l y , D r e w e t al. ~'-'e a n d S h i e l d s a n d L e w i s v27 a l m o s t s i m u l t a n e o u s l y r e p o r t e d a t e c h n i c for a c h i e v i n g d e e p h y p o t h e r m i a b y p e r f u s i n g b o t h the systemic a n d p u l m o n a r y circuits, using the a m m a l s own lungs for oxygenation a n d a h e a t e x. c h a n g er on t h e s y s t e m i c side. C o r e t e m p e r a t u r e s m t h e 1 0 - 2 0 C. r a n g e w e r e a c h i e v e d , a l l o w i n g p e r i o d s of c o m p l e t e c i r c u l a t o r y o c c l u s i o n u p

~4~

S'~VAN A N D P A T O N

to 50 m i n u t e s w i t h r e c o v e r y . D r e w a n d A n d e r s o n *zs d e s c r i b e d t h e first p a t i e n t s to u n d e r g o this ~,,pe of cooling for c a r d i a c s u r g e r y a n d m a n y others h a v e c o n t i n u e d to explore this m e t h o d for t h e r e p a i r of a v a r i e t y of c o n g e n i t a l defects. A final m e t h o d of cooling w h i c h has r e c e i v e d clinical trial was d e s c r i b e d b y Parkins et al. 7G T h i s consisted of p c r f u s i o n of t h e b r a i n w i t h v e r y cold blood. A l t h o u g h t h e r e c t a l t e r n p e r a t u r e r e m a i n e d n e a r 30 C., b r a i n t e m p e r a t u r e s of 18-20 C. a l l o w e d c i r c u l a t o r y occlusion f o r p e r i o d s u p to 30 m i n u t e s w i t h recovery. K i m o t o et a I ) "-''~ d e s c r i b e d 5 p a t i e n t s in w h o m this m e t h o d was emp l o y e d for r e p a i r of c o n g e n i t a l c a r d i a c defects. T h e i r l o n g e s t occlusion p e r i o d was 13 m i n u t e s . COI",~PLI~'rIoNs OF HYPOTIIER~lJb,, T h e c o m p l i c a t i o n s of external coo • 1"m g can b e l a r g e l y p r e v e n t e d , b u t continuous c a u t i o n a n d c a r e f u l a t t e n t i o n to detail m u s t b e m a i n t a i n e d . 1. Periph,m'al n e r v e paralysis m a y o c c u r as t h e result o f p r o l o n g e d i m m e r s i o n a n d m a y b e a v o i d e d b y not a l l o w i n g the arms or legs to r e m a i n in t h e icew a t e r for l o n g e r t h a n 30 minutes. R e c o v e r y is almost a l w a y s c o m p l e t e . 2. Burns of t h e sacral a r e a or a r o u n d t h e e l e c t r o c a r d i o g r a p h n e e d l e s are distressing, a n d m a y c a u s e u n d e s i r a b l e m o r b i d i t y . T h e f o r m e r is a lesiou d u e to i s c h ~ i a f r o m t h e p r e s s u r e of t h e b o d y w e i g h t c o m b i n e d w i t h d i a t h e r m y heat; t h e l a t t e r is p r o b a b l y a c o m p l i c a t i o n of t h e u s e of e I e c t r o c a u t e r y . Since these b r a n s a r e d e e p a n d t h e h e a l i n g slow, e a r l y g r a f t i n g is u s u a l l y il)dicated. 3. V e n t r i c u ] a r fibrillation is m o s t d a n g e r o u s if it occurs in a p a t i e n t n o t u n d e r g o i n g a t h o r a c i c o p e r a t i o n . V a r i o u s agents m a y b e of p r o t e c t i v e v a l u e as discussed above. I f t h e c h e s t is open, e l e c t ~ c a I defibrillation is a h n o s t u n i v e r s a l l y successful. 4. P o s t o p e r a t i v e h e m o r r h a g e occurs m o r e f r e q u e n t l y , w c believe, t h a n in n o r m o t h e r m i c p a t i e n t s . This is n o t d u e so m u c h to a n y c h a n g e in the clotting m e c h a n i s m c a u s e d b y h y l ) o t h e r m i a , b u t r a t h e r to t h e fact t h a t t'he w o u n d is m a d e a n d closed w h e n t h e blood p r e s s u r e is d e p r e s s e d . U p o n w a r m i n g , small arterial b | c e d e r s n o t p r e v i o u s l y m a n i f e s t , m a y o p e n up. M e t i c u l o u s h e m o s t a s i s in m a k i n g t h e incision is fires i m p e r a t i v e , a n d w a r m i n g t h e p~ltient on the t a b l e w i t h d i a t h e r m y so t h a t t h e blood p r e s s u r e rises b e f o r e t h e incision is closed is also helpful. T h e r e s h o u l d b e no hesitation in r e - e x p l o r i n g to find a n d ligate t h e b l e e d i n g p o i n t s as soon as it b e c o m e s e ~ d e n t t h a t b l o o d loss is c o n t i n u i n g at an excessive r a t e postoperatively. 5. O a s t r i c ~ I a t a t i o n in t h e i m m e d i a t e p o s t o p e r a t i v e p e r i o d m u s t b e w a t c h e d for, a n d m t u b a t m n r e s o r t e d to if n e c e s s a r y . 6. Pulmonm~y c o m p l i c a t i o n s s u c h as atelectasis or p n e u m o n i t i s o c c u r wifll a b o u t t h e s a m e f r e q u e n c y as in t h o r a c i c p r o c e d u r e s d o n e d u r i n g n o r m o t h e r m i a . . at* t* H y 1) o t h e r m i a does n o t s e e m to p r e d i s p o s e t h e p a t i e n t to r e s p l r a t. o r y m~ec runs. INDIC~TIor,:s FOR HYr'o111m~Mr^ H y p o t h e r m i a r e d u c e s m e t a b o l i c rate, slows t h e h e a r t , a n d causes h y p o t e n s~on. Based on t h e s e p h ) s m l o g m effects, s o m e p o t e n t i a l uses of this m o d a h t y a r e s u g g e s t e d below. It m u s t b e n o t e d t h a t s o m e of these h a v e a c t u a l l y b ~ n

CUIlllENT

STATUS

oF

IIYPOTItERMIA

243

d e m o n s t r a t e d to have merit, while others remain to be investigated. Those w h i c h / l a v e ah--eady had clinical e n d o r s e m e n t are m a r k e d by an asterisk. 1. To reduce oxygen need in acute or reversible conditions causing general or local hypoxia. A. Acute p u l m o n a r y diseases (ateleetasis, p n e u m o n i a ) . B. P u l m o n a r y or cerebral embolus. C. Post-Cardiac arrest encephalopathy. °D. Acute head trauma. *E. D e l i b e r a t e t e m p o r a r y interruption of blood supply. 1. Total interruption. °a. C a r d i a c Sm'gery. 2. Regional Interruplion. °a. D e s c e n d i n g aorta. °b. C e r e b r a l arteries. *e. H e p a t m vessels. *d. Renal vessels, °F. Ischemie extremity. II. To cause physmlogm h y p o t e n s m n a n d / o r local hemostasis. A. To diminish hemorrhage. ° 1. Brain surgery. 2. Skin grMting. *3. G a s t r o - d u o d e n a l hemorrhage. B. To c o u n t e r a c t h y p e r t e n s i v e crises, 1. E n c e p h a l o p a t h y , 2. Eclampsia. 111. To increase tolerance to hypotension. A. Sep~c shock, B. Myocardial infarction. IV. T o c o m b a t h y p e r p y r e x i a . *A. Thyrotoxicosis. B. Third-ventricle h e m o r r h a g e . C. H e a t stroke. *D. A n y febrile illness. V. To decrease anesthetic or operative risk. *A. In p r e s e n c e of cardiac disease. I, T a c h y e a r d i a (slows h e a r t r a t e ) . 2. C a r d i a c dilatation (mitral, etc.) - ( l o w e r cardiac o u t p u t ) *B. Liver disease (cirrhosis). * e . C h r o n i c p u l m o n a r y disease. "D. Any debilitated patient. VI. T o help c o m b a t infee~on.

B. Peritoni~s. VII. Burns. V l l I. T h e transplantation of tissues. A. Kidney. B. Liver.

244

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C. D. E. F. G. H.

Gastro-intestinal tract. Skin. Arteries. Cornea. Bone. Other. H~'POTHEnMta AND INFECTION

I t h a s b e e n s h o w n t h a t m a n y of t h e e l e m e n t s of i n f l a m m a t i o n s u c h as h y p e r e m i a , edema, leukocytosis, an d local necrosis m a y b e m a r k e d l y r e d u c e d b y t h e use o f h y p o t h e r m i a , la°-~al A t t h e s a m e t i m e , t h e p r o l i f e r a t i o n o f s o m e o r g a n i s m s i n c l u d i n g s t r e p , h e m o I y t i c u s is g r e a t l y r e t a r d e d . E i s e m a n e t a l ) 3~ ~ u g g e s t e d t h a t t h e i n v a s i v e p r o p e r t i e s of t h e o r g a n i s m w e r e r e t a r d e d m o r e t h a n t h e d e f e n s e m e c h a n i s m s o f t h e host, a n d F e d o r e t al. ~az r e a c h e d a sm~ilar c o n c l u s i o n t h a t " ' . . . t h e r a t i o n a l e for t h e use o f h y p o t h e r m i a in c o m b a t t i n g i n f e c t i o n is r e a s o n a b l e . " T h e c l i n i c a l trials o f this m e i h o d h a v e as y e t b e e n limited. HYI?o'rti~,IIA

AND SHOCK

Does the h y p o t h e r m i c individual tolerate h e m o r r h a g i c shock better or w o r s e t h a n t h e n o m n o t h e r m i c ? T h e e v i d e n c e is c o n f l i c t i n g . O n e o f t h e s i m p l e r , m o r e d e f i n i t e r e l a t i o n s h i p s is t h e e f f e c t o f c o l d in ]im~ting s u r f a c e h e m o r r h a g e or r e g i o n a l e d e m a . T h i s p r o p e r ~ has b e e n ~ o w n s i n c e t h e t i m e s o f H i p p o c r a t e s . D u n c a n a n d B l a l o c k ~a':~ f o u n d in c r u s h e d e x t r e m i t y e x p e r i m e n t s t h a t t h e a p p l i c a t i o n of i c e r e s u l t e d i n less s w e l l i n g a n d i n c r e a s e d s u r v i v a l if it w e r e m a i n t a i n e d t h r o u g h o u t t h e c o m p r e s s i o n p e r i o d . I f t h e l e g w e r e c r u s h e d a n d ice a p p l i e d thir~g m i n u t e s l a t e r , t h e r e w a s l i t t l e o r n o etfect. M o r e r e c e n t l y , VVilhnan a n d H a n l o n ~a5 c l e a r l y d e m o n s t r a t e d t h a t h e m o r r h a g e f r o m a s p l i t - t h i c k n e s s g r a f t site w a s less w h e n c o l d c o m p r e s s e s w e r e a p p l i e d . T h u s , t o w h a t e v e r e x t e n t h y p o t h e r m i a , e i t l m r r e g i o n a l o r gencq~d, ases b l o o d loss o r p l a s m a e n t r a v a s a t i o n in t h e i n j u r e d i n d i v i d u a l , to t h a t e x t e n t it is b e n e f i e i a l in p r e v e n ~ n g h y l ~ o v o l e m i c s h o c k . xeVilson et aI. 1°~ s t u d i e d t h e r e s p o n s e of d o g s t o a r a p i d a r t e r i a l h e m o r r h a g e o f 35 p e r c e n t o f t h e m e a s u r e d b l o o d v o l u m e . Sud~ a n i m a l s l i y e d ff b l e d w h e n n o r m o t h e r m i c ; b u t , if b l e d w h e n h y p o t h e r m i e , o n l y 18 p e r c e n t s u r v i v e d . I n o t h e r w o r d s , a c e r t a i n h e m o r r h a g e w h i c h k i l l e d n o w a r m dogs, ~ l l e d g 2 p e r cent of h y p o t h e r m i e dogs. O n t h e o t h e r herod, t h e a p p a r e n t b e n e f i t o f h y p o t h e r m i a in t h e , r e a t m e n t of s e p t i c s h o c k is m e n ~ o n e d e l s e w h e r e in t h i s p a p e r . I t is o b v i o u s t h a t m u c h r e m a i n s to b e l e a r n e d e o n c e n l i n g t h e r d a t i o n s h i p o f h - q ~ o t h e r m i a to s h o c k - l i k e s t a t e s o f v a r i o u s k i n d s . SURGICAL USES OF M O D E R A T E H

ERIVIIA

A. As a Teohnic for Open,Heart Surgery C e r t a i n f u n d a m e n t a l t e c h n i c s f o r o p e n - h e a r t s u r g e r y h a v e b e e n e v o l v e d . ~8 T h e p a t i e n t is v e r y c a r e f u l l y p o s i t i o n e d so t h a t t h e c a r d i o t o m y will b e a t l h e m o s t s u p e r i o r a s p e c t o f t h e h e a r t . T h u s , f o r c l o s u r e o f an a u r i c u l a r d e f e c t t h e

CUBIIENT STATUS OF H

ER2,.~LA

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p a t i e n t is t i p p e d to t h e left w i t h h e a d e l e v a t e d ; f o r p u l m o n a r y v a l v e su to t h e r i g h t w i t h h e a d m a r k e d l y e l e v a t e d ; etc. T h e air m a y t h u s e s c a p e f r o m t h e u p p e r m o s t d m m b e r s o f tile h e a r t t h r o u g h t h e c a r d i o t o m y a t t h e °time o f retreat from the heart. A t t h e o n s e t o f c i r c u l a t o r y o c c l u s i o n , t h e h e a r t is s l o w e d b y t h e i n j e c t i o n of 1 : 4 0 0 0 n e o s t i g m i n e g i v e n b y c o r o n a r y p e r f u s i o n , oF r e m 1-a~ ee. o f t h i s solution will s l o w b u t n o t s t o p t h e h y p e r ~ o p h i e d h e a r t . T h e h e a r t will s t a y p i n k a h n o s t t h r o u g h o u t t h e o c c l u s i o n p e r i o d , a n d will r e s u m e its b e a t r e a d i l y o n c e c o r c n a r v c i r e u l a H o n is a l l o w e d . 5° T h e r o o t o f flxe a o r t a is a l w a y s c l a m p e d ( e x c e p t w i t h a o r t i c s t e n o s i s ) in o r d e r t o p r e v e n t coronax 7 M o o d f l o w d u r i n g o c c l u s i o n . T h i s h e l p s p r e v e n t coronary air embMism, maintains the bra a, a n d in d i m i n i s h i n g t h e c o r o n a r y r e t u r n to t h e h e a r t i n s u r e s a di N o p e r a t i v e field a n d Gnus a s h o r t e r o c c l u s i o n p e r i o d . ~3, T h e p e r i o d o f c i r c u l a t o r y ocmlnsion s h o u l d n o t e x c e e d six m i n u t e s a n d ~ t n o t e x c e e d eight° I f it is a p p a r e n t t h a t t h e c o m p l e t e o p e r a t i o n c a n n o t b e acccmpliM~ed in t h i s p e r i o d of t i m e , t h e p r o c e d u r e s h o u l d b e s t o p p e d a n d es f r o m t h e h e a r t e f f e c t e d , b r i n g i n g o u t t h e l o o s e e n d s o f an), u n f i n i s h e d s u t u r e s . C i r c u l a t i o n is r e s t o r e d . A f t e r 10 o r 15 m i n u t e s to a l l o w r e = e s t a b l i s h m e n t o f n o r r n a l m y o c a r d i M m e t a b o l i s m , t h e o c c l u s i o n m a y b e r e p e a t e d . A t l e a s t i 0 to 12 s a f e m i n u t e s o f i n t r a e a r d i a e t i m e m a y Cnus b e a c h i e v e d . 5s 1. I s o l a t e d p u l m o n a r y stenosqs.- T h e r e s u l t s o f t r a n s v e n ~ i c u l a r i n s t r u m e n t a l incision a n d d i l a t a t i o n o f t h e c o n g e n i t M l y s t e n o s e d p u l m o n a r y valve, a l t h o u g h often quite satisfactory, have nevertheless frequently been disappointing when objective postoperative studies were performed. The stenosis has been found, a t t i m e s , to b e e s s e n t i M I y u n r e l i e v e d . ~ U n d e r d i r e c t vision d u r i n g c e s s a t i o n of c i r c u l a t i o n , ~ne p u l m o n a r y artery- m a y b e o p e n e d , t h e f u s e d f u n n e l - l i k e v a l v e i n c i s e d in t h r e e d i r e c t i o n s all t h e w a y to t h e r i n g . T h e he,~xt is a l l o w e d to fill w i t h M o o d as t h e c l a r n p is r e p l a c e d o n t h e p u l m o n a r y a r t e ~ - . T h e incision in t h e a r t e r y m a y enen b e s u t u r e d w h i l e c i r c u l a t i o n p r o c e e d s . T h e r e s u l t s o f this o p on a r e emiv~ently s a t i s f a when s~died later b y o b j e c t i v e m e a s u r e m e n t s . T h e g r a d i e n t f r o m r i g h t v e n t r i c l e to p u l m o n a r y artec., is r e d u c e d t o less t h a n 20 m m . / H g in a l m o s t e v e r y case, a n d t h e ~'ight v e n t r i e u l a r p r e s s u r e is u s u a l l y f o u n d to b e less t h a n 4 0 m m ~As C ,satery infundibulm" hyper m a y c a u s e s o m e t e m p o r a r y r e s i d u a l g r a d i e n t in this exea, b u t as t h e t h i c k n e s s o f t h e v e h i c u l a r m y o e a r d i u m in t h e r i g h t o u t flow t r a c t d e c r e a s e s f o l l o w i n g t h e r e l e a s e o f t h e v a l v u l a r stenosis, this g r a d i e n t g r a d u a l l y d i s a p p e a r s ~ q t h tame; a n d a f t e r t w o or t h r e e ),ears, t h e d ~ a m i c s will b e f o u n d t o b e e s s e n t i M I y n o r m M . S o m e v a l v u l a r r e g ~ t a t i o n mG~, b e c r e a t e d , b u t it h a s n o t b e e n f o u n d n e c e s s a r y to r e - o p e r a t e on a n y p a t i e n t s b e cause of residual infundibular obs~uetion. A t t h e U n i v e r s i t y o f C o l o r a d o 69 c o n s e c u t i v e p a N e n t s h a v e h a d a n o p e n repair of isMated pulmon~y valvular stenosis ~qthout mortality, and 9 patients h a d o p e n r e s e c t i o n o f i s o l a t e d i n f u n d i b u l a r stenosis, w i t h o n e d e a t h . T h i s t e c h n i q u e is n o w w i d e l y u s e d in t h e U n i t e d S t a t e s a n d E u r o p e . oo. A t r i a l scT~tal d e f e c t . - - S u t u r e e l o s u r e o f t h e h i g h s e e u n d u m a n d f o r a m e n ~:vale d e f e c t s c a n b e easily a c h i e v e d u n d e r h y p o t h e r m i a . E v e n t h e v e r y l a r g e

246

SVCAN AND PATON

defects do not need placement of prosthetic devices since the huge right atria p r o v i d e a m p l e w a l l t o a l l o w c l o s u r e b y c o n t i n u o u s s u t u r e . T h e p r e s e n c e of a b e r r a n t p u l m o n a r y v e n o u s d r a i n a g e o c c u r s in a b o u t 15~ o f p a t i e n t s , b u t o p e r a tive t e c t m i q u e s to o v e r c o m e this a d d i t i o n a l a n o m a l y h a v e b e e n d e s c r i b e d b y b o t h L e w i s e t a12 a~ a n d S w a n e t el. ~°4.~4° G r e a t c a r e m u s t b e t a k e n to a v o i d 6ue i n a d v e r t e n t t r a n s p l a n t a t i o n o f t h e i n f e r i o r c a v e to t h e left a u r i c l e , a n d t h e a i r m u s t b e t h o r o u g h l y e v a c u a t e d f r o m tile l e f t v e n t r i c l e b e f o r e t h e final s t i t c h is t a k e n to a v o i d a i r e m b o l i s m . I f m o r e t h a n six m i n u t e s is r e q u i r e d f o r the p r o c e d u r e , multiple circulatory occlusions p e r m i t a d e q u a t e inh-acardiac time. Acorn-ate p r e o p e r a t i v e d i a g n o s i s , of c o u r s e , is e s s e n t i a l s i n c e it is u n d e s i r a b l e f o r t h e s u r g e o n to b e o p e r a t i n g w i t h h y p o t h e r m i a a l o n e a n d t h e n find t h e lesion to b e a p r i m u m t y p e d e f e c t f o r w h i c h h e w o u l d like to u s e t h e p u m p o x y g e n a t o r . S u c h d i a g n o s t i c a c c u r a c y , h o w e v e r , is q u i t e p o s s i b l e x~dtl~ m o d e r n c a r d i o l o g i c a l e v a l u a t i o n , aaa I n t h e e a r l y d e v e l o p m e n t of t h e t e c h n i q u e , S w a n e t al., ~a o p e r a t e d u p o n 43 p a t i e n t s -,viffJ 7 d e a t h s . S u b s e q u e n t l y , 137 a d d i t i o n a l p a t i e n t s w e r e r e p a i r e d w i t h o n l y 3 d e a t h s . I t w o u l d s e e m , t h e r e f o r e , t h a t t h e c u r r e n t r i s k o f this t e c h n i c is s o m e w h a t l e s s t h a n t w o p e r cent. D e r r a , x4= B r o m , 1°~ a n d B e d f o r d e t al. ~4a h a v e c o n t i n u e d to u s e this m e t h o d w i t h e x c e l l e n t results. 3. Trilogy o~ Fallot. S i n c e t h e T r i l o g y of F a l l o t consists e s s e n t i a l l y o f t h e c o m b i n a t i o n o f v a l v u l a r p u l m o n i c stenosis a n d a f o r a m e n o v a l e s e p t a l d e f e c t , it w a s o n e o f t h e e a r l i e s t o f t h e c y a n o t i c f o r m s of c o n g e n i t a l h e a r t d i s e a s e to b e a t t a c k e d s u r g i c a l l y w i t h o p e n t e c h n i q u e . A t first it w a s t h o u g h t t h a t relief, of Hae p u l m o n i c s t e n o s i s a l o n e m i g h t p r o v e to b e a d e q u a t e t r e a t m e n t if t h e p o s t o p e r a t i v e f a l l in r i g h t v e n t r i c u l a r p r e s s u r e r e s u l t e d in a s i g n i f i c a n t d e c r e a s e in t h e r i g h t - t o - l e f t s h u n t t h r o u g h t h e ah-ial s e p t a l d e f e c t . I n d e e d , this r e s u l t d o e s o c c u r in m a n y p a t i e n t s . An o c c a s i o n a l s u c h p a t i e n t m a y n e e d a s e c o n d s t a g e c l o s u r e o f t h e s e p t a l d e f e c t . Since, h o w e v e r , b o t h d e f e c t s c a n b e c o m p l e t e l y c o r r e c t e d a t a s i n g l e o p e r a t i o n u s i n g m u l t i p l e c i r c u l a t o r y o c c l u s i o n s at l o w risk, S w a n e t al., aaa a f t e r e x p e r i e n c e w i t h 23 s u r g i c a l p a ~ e n t s , r e c o m m e n d

4. A o ~ i c s t e n o s i s . - - A l t h o u g h b y 1954 t h e o p e n a t t a c k on t h e p u l m o n a r y v a l v e h a d b e c o m e c o m m o n p l a c e , s u r g e o n s h e s i t a t e d to u s e t h e s a m e a p p r o a c h to t h e a o ~ c v a l v e f o r f e a r o f air e m b o l i s m to t h e c o r o n a r y o r c e r e b r a l ch~cula tions. E ~ e r i m e n t a ] o b s e r v a t i o n s in d o g s i n d i c a t e d t h a L e v e n ~ o u g h t h e coro n a r y o s t i a w e r e e x p o s e d to t h e r o o m air, t h e r e w a s n o t a t e n d e n c y f o r a i r e m b o l i s m to t h e c o r o n a r y o r c e r e b r a l c i r c u l a t i o n s . A c c 6 r d i n g l y , S w a n mud K o r ~ ~45 r e p o r t e d t h e first s u c c e s s f u l o p e n o p e r a t i o n o n t h e a o r t i c v a l v e in m a n u s i n g inflow o c c l u s i o n d u r i n g h y p o t h e r m i a . S o o n a f t e r w a r d s , L e w i s et al. ~46 s u c c e s s f u l l y e m p l o y e d a n a l m o s t i d e n t i c a l t e d m i c in o n e o f t w o p a t i e n t s . S u b sequent]y, of course, with the development of successful pump-oxygenators, most aortic vaIvular surgery has been done during total extracorporeal bypass. T h e use o f hyqgotherrnia a l o n e , h o w e v e r , f o r c o n g e n i t a l stenosis of t h e a o r t i c vzdve a n d f o r e a r l y a c q u i r e d v a l v u l a r d i s e a s e h a s c o n t i n u e d to h a v e s u p p o r t ors. a~T T h e c o n g e n i t a l l y f u s e d , o f t e n b i c u s p i d a o r t i c v a l v e c a n b e c a r e f u l l y a n d a c c u r a t e l y i n c i s e d in t h e c o m m i s s u r e s w i t h i n t h e six m i n u t e t i m e l i m i t T o c r e a t e r e g u r g i t a t i o n o f t h e a o r t i c v a l v e is d i s a s t r o u s : f h e r e f o r e , t h e s e incisions

CU~,RENT

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HYPOTHERIVIIA

247

m u s t b e m a d e precisely, l e a v i n g i n t a c t c o m p e t e n t cusps. T h e occasional p a t i e n t w i t h i n f u n d i b u l a r aortic stenosis is b e t t e r o p e r a t e d u p o n d u r i n g total b o d y T h e a d d i t i o n of a c o n s t a n t p e r f u s i o n of b l o o d into t h e c o r o n a r y c.;rcu]ation from a b l o o d reservoir w a s s t u d i e d a n d t h e n a t t e m p t e d c l i n i c a l l y b y S h u m w a y et al.,~:4 S p e n c e r e t al., *4s a n d M a l o n e y e t al. a*9 No gr e a t e xte nsion in p e r m i s sible occlusion t i m e w a s o b t a i n e d , the m o r t a l i t y a n d m o r b i d i t y rates p a r a l l e l e d those p a t i e n t s n o t r e c e i v i n g p e r f u s i o n , a n d t h e t e c h n i c h a d the d i s a d v a n t a g e of i n c r e a s i n g t h e b l o o d in t h e o p e r a t i v e f e l d . F o r tl~ese reasons, t h e m e t h o d d i d n o t r e c e i v e w i d e a c c e p t a n c e . H o w e v e r , the use o f t h i s t e c h n i c d u r i n g c a r d i a c a r rest a n d extracorporeaI c i r c u l a t i o n is of d i s t i n c t v a l u e a n d is des c r i b e d below. T h e e m T e n t e x p e r i e n c e a t t h e U n i v e r s i t y of C o l o r a d o i n c l u d e s o p e n operation d u r i n g h y p o t h e r m i a on P,3 p a t i e n t s w i t h c o n g e n i t a l v a l v u l a r disease, w i t h 2 deaths. I n a d d i t i o n , 5 p a t i e n t s w i t h ac
B i g e l o w 1°~ w a s h e first to u r g e t h e use of h>q)othermia as an a d j u n c t in t h e s u r g e r y for far a d v a n c e d mitraI d i s e a s e w i t h c a r d i a c f a ilur e , a n d s u c c e s s f u l l y t r e a t e d o b v i o u s l y high-ri~< p a t i e n t s w h o h a d m a s s i v e c a r d i a c d i l a t a t i o n . After r e l i e f of t h e i r m i t r a l o b s t r u c t i o n , t h e y w e r e m u c h i m p r o v e d c l i n i c a l l y a n d t h e i r h e a r t size r e d u c e d r e m a r k a b l y . At the U n i v e r s i t y of Colorado, w e h a v e h a d s i m i l a r e x p e r i e n c e s w i t h 8 m i ~ a I patients. T h e h y p o t h e r a n i a r e d u c e s t h e h e a r t rate, c a r d i a c o u t p u t a n d w o r k loa d of t h e h e a r t a n d m i n i m i z e s t h e dose o f n a r c o t i c a g e n t s n e c e s s a r y b e c a u s e o f its a n e s t h e t i c action. I n a d d i t i o n , a s a f e t y f a c t o r is p r o v i d e d a n d if d e s i r a b l e f or a n y reason the c i r c u l a t i o n can b e s a f e l y a r r e s t e d for 6 to 8 m i n u t e s . F o r t h e s e reasons, w e h a v e c h o s e n to u s e h y p o t h e r m i a for p a t i e n t s w i t h l a r g e p a t e n t d u e t u s , a o r ~ c o - p u ] m o n a r y fistula. total a n o m a l o u s v e n o u s d r a i n a g e , t r i c u s p i d atresia, tetralogy, a n d transposition. F o r s i m i l a r reason, h y p o t h e r m i a h a s b e e n u r g e d f o r p a t i e n t s m~dergoing s u r g e r y for a w i d e varie~,t of dis e a se s in g e n e r a l a n d t h o r a c i c surgery. B r e w e r and K i n g aS° e m p h a s i z e d ats ~:se in t h e a g e d a n d d e b i l i t a t e d , a n d E i s e m a n et al. *~I a n d R e e v e s a n d Lew~s, a~2 for various ge ne r a ] surgma] c o n d l t m n . , p a r t i c u l a r l y cirrhosis of t h e liver. C, A s a n A d i u n c t f o r S u

o[ t h e A o r t a

T h e experimental studies indicating that moderate hypothermia markedly p r o l o n g s the period d u r i n g w h i c h t h e d e s c e n d m g aorta m a y b e c l a m p e d w i t h out d a m a g e to t h e cord or to the k i d n e y s h a v e b e e n d e s c r i b e d . T h i s be nef ic ia l effect h a s b e e n u s e d c l i n i c a l l y b y a n u m b e r of s u r g e o n s to p e r m i t the p r o l o n g e d

248

S W A N AND r A T O N

c l a m p i n g n e c e s s a r y f o r t h e r e s e c t i o n of c o a r e t a t i o n o r a n e u r y s m s o f t h e d e s c e n d i n g a o r t a . T h u s , J u l i a n e t al. anz d e s c r i b e d t h i s c l i n i c a l a p p l i c a t i o n in 2 p a t i e n t s w i t h a n e u r y s r n a n d 6 w i t h c o a r c t a t i o n . D e B a k e y , e t al. x~ a n d G w a t h m e y e t al. ~-~ h a v e h a d e x t e n s i v e s a t i s f a c t o l y e x p e r i e n c e w i t h t h i s t e c h n i q u e . A t t h e U n i v e r s i t y o f C o l o r a d o i n 1947, a p a t i e n t s u f f e r e d p a r a p l e g i a f o l l o w i n g r e s e c t i o n o f c o a r e t a t i o n . S i n c e 1954, t h e r e f o r e , all a d u l t p a t i e n t s w i t h c o a r c t a t i o n h a v e b e e n c o o l e d as a p r o t e c t i v e m e a s u r e a g a i n s t c o r d d a m a g e . T o d a t e , in 20 p a t i e n t s so ta'eated, n e u r o l o g i c i n j u r y h a s n o t o c c u r r e d . TIlE CONIBINED USE OF HYP

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AND E X T R A C O R P O ~ A L

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T h e o b v i o u s f a c t o r l i m i t i n g t h e u s e o f h y p o t h e r m i a a l o n e is t h e t i m e a w t i l able for the pe~orrnance of intracardiac repair and reconstruction. Complic a t e d a n d difficult lesions n e e d c o n s i d e r a b l e time for their repair, a n d therefore s m a n d a t o r y in r e p a i r i n g s u c h d e f e c t s . H o w ever e. o b t a i n e d f r o m t h e c o m b i n a t i o n o f e x t r a -

1. Safety Factors A c o l d h e a r t is b e t t e r a b l e t o w i t h s t a n d a n o x i a t h a n a w a r m o n e , a n d t h e r e fore a s a f e t y m a r ~ n exists in t h e e v e n t of a n y u n f o r e s e e n m i s h a p d u r i n g t h e p e r f u s i o n . A l s o t h e h e a r t r a t e is s l o w e d b y t h e h y p o t h e r - m i a , a n d i f c a r d i a c arr e s t is n o t d e s i r e d , a t l e a s t t h e s u r g e o n h a s t h e b e n e f i t o f w o r k i n g w i t h a s l o w l y b e a t i n g h e a r t . If, h o w e v e r , t h e h e a r t d o e s s t o p , t h e g r e a t l y r e d u c e d m e t a b o l i c demm,~ds o f t h e c o l d h e a r t e n a b l e a l o n g e r p e l ~ n i s s i b l e t i m e b e f o r e ¢,iae r e t t t r n o f a d e q u a t e c i r c u l a ~ o n w i t h o u t s u b s e q u e n t d i ~ c u l ~ , . A d d i t i o n a l p r o t e c t i o n is also d e d to f h e brain.

2. R e d u c e d O x y g e n R e q u i r e m e n t T h e e x t e n t o f t h e r e d u c t i o n in o x y g e n r e q u i r e m e n t d e p e n d s u p o n t h e d e g r e e o f h y p o t h e ~ i a b u t p e w i t s t h e u s e of a s m a l l e r o x y g e n a t o r w i t h a l o w e r b l o o d f l o w a n d c o n s e q u e n t l y less ~ a u m a t o t h e b l o o d . T h e d e c r e a s e in Hae a m o u n t o f b l o o d r e q u i r e d is also a d e f i m e c o n s i d e r a t i o n i n v i e w o f t h e increasing number of open-heart operations being done. 3. G'lm~2ge in D

I f flae p a t i e n t is first c o o l e d i n t h e t u b a n d s u b s e q u e n d y a t t a c h e d t o t h e pumpe n a t o r , i t is p o s s i b l e , o n o c c a s i o n , t o d i s p e n s e w f t h t h e p u m p - o x y g e n a t o r , i f i t is f o u n d d a a t t h e d i a g n o s i s is s u c h t h a t t h e o p e r a t i o n c o u l d b e d o n e a d e q u a t e l y w i t h h y p o t h e r m i a a l o n e . T h e p a t i e n t n e e d n o t t h e n b e exp o s e d t o h a z a r d s b o t h k n o w n a n d unknox~qa o f p e r f u s i o n .

4. Technical A d v a I t is p o s s i b l e to s t o p t h e p e r f u s i o n c o m p l e t e l y in a c o o l e d p a t i e n t f o r s o m e m i n u t e s if t h e s i t u a t i o n s h o u l d d e m a n d a c o m p l e t e l y d r y , b l o o d l e s s field, x#¢'ith t h e p a t i e n t ' s t e m p e r a t u r e a t 3 0 C. t h e p e r f u s i o n c a n b e s t o p p e d for at l e a s t five m i m l t e s w i t h o u t a n y f e a r o f c e r e b r a l d a m a g e , a n d this m a n e u v e r c a n g i v e v a l u a b l e a s s i s t a n c e to t h e s u r g e o n . T h i s p r o c e d u r e m a y b e r e p e ~ t e d s e v e r al t i m e s d u r i n g a l o n g p e r f u s i o n if n e c e s s a r y , b u t c a r e s h o u l d b e t a k e n to s e e

(TtJltltgNq" STATUS

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I~IYI~OTHERNIIA

t h a t the e l e c t r o e n c e p h a l o g r a m returns to normal b e t w e e n each period of culatory arrest. The w i t h extracorporeal circulation does necessa technique. T h e hypofl~ermia can b e d u c e d b y one of three methods. E i t h e r the p a t i e n t is cooled in an ice-water

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because the p a t i e n t has to be c a n n u l a t e d in o r d e r t o be cooled. T h e third " m e t h o d for the induction of deep h y p o t h e r m i a as d e s c r.:i b e d b y D r e w , I 2 6 Slnelds and Lewis, r-'r is detailed below. In general, t h e use of a h e a t exchanger has b e c o m e the m o r e acceptable technic b e c a u s e of the r a p i d i t y with whicia b y p o t h e r m i a can be induced, and because of the ease with w h i c h t h e p a t i e n t can be r e w a r m e d at the e n d of the p r c c e d u r e : T h e induction of h y p o t h e r m i a in t]~is m a n n e r results in definite dif-

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culatib: is variable. THE USE OF DEEP HYPO~tF~).~IA FOIl OPEN-HF-J~_I~T SUI~G~Y i n 1954 Go]lan 27 w a s the first to using a n e x ~ a c o r p o r e a l eircuit~ T h D e e p h~:-,pothermia m a y be i n d u c e d b y the use of a s t a n d a r d :a ! cardiopulmonarv, bypass~ i n c l u d i n g a l i e a t exchanger, I5r or us1'1 t's own lungs as an a u t o g e n o u s o x y g e n a t o r with s e p a r a t e e i r c u i ~ for t h e p u l m o n i e and systemic e i r c u l a ~ o n s . T h e main a d v a n t a g e o f using d e e p h ~ 0 t h e ~ i a is the e x ~ e m e ] y d r y mo~onless surgical f i d d w h i c h can b e o b t a i n e d at t e m p e r a tures a r o u n d 15 C, x~th total cessation of circulation a n d r ~ ) i r a t i o n ~oI periods

250

S~#t/kl'q A N D P & T O N

of 4 5 - 6 0 m i n u t e s . It a p p e a r s t h a t c e s s a t i o n o f t h e c i r c u l a t i o n for 45 m i n u t e s is s a f e in t h e h u m a n , at t e m p e r a t u r e s not h i g h e r t h a n 15 C. E v e n a t t h e s e t e m p e r a tu_res t h e r e is c o n s u m p t i o n o f o x y g e n , - - a n d it m a y b e a d v a n t a g e o u s to m a i n t a i n the c i r c u l a t i o n w i t h t h e p u m p - o x y g e n a t o r r a t h e r than o b t a i n c o m p l e t e cessation of c i r c u l a t i o n . T h e a d v a n t a g e s o f u s i n g d e e p h y l p o t h e r m i a are: 1 ) T h e r e is m a x i m a l p r o t e c t i o n f o r t h e h e a r t d u r i n g p e r i o d s o f a n o x i a a n d / o r c a r d i a c arrest. 2• ) I t is p o s s i b l e to h a v e a p r o l o n g e d p e r i o d of total a r r e s t o f c i r c u l a t i o n a n d r e s p i r a t i o n w i t h a n e x t r e m e l y d r y a n d m o t i o n l e s s s u r g i c a l field. 3 ) I f t h e D r e w t e c h n i q u e is u s e d t h e q u a n t i t y of b l o o d n e c e s s a r y to p r i m e t h e c i r c u i t is o n l y 1 , / 0 0 to 1,500 co., a n d t h e a b s e n c e o f a n o x y g e n a t o r r e s u l t s i n d i m i n i s h e d t r a u m a to the b l o o d . H o w e v e r , t h e m e t h o d is not w i t h o u t d i s a d v a n t a g e s . I f t h e p a t i e n t ' s l u n g s a r e d i s e a s e d t h e n flmir e t t l c i e n c y as a n o x y g e n a t o r m a y b e i m p a i r e d . I n u ~ it is p r o b a b l y i n a d v i s a b l e to use this t e c h n i q u e in p a t i e n t s w i t h p u l m o n a r y h y p e r t e n s i o n a n d p o s s i b l e p u l m o n a r y v a s c u l a r c h a n g e s . In t h e e x p e r i m e n t a l a n i m a l p u l m o n a r y e d e m a is not u n c o m m o n a l t h o u g h t h e p u l m o n a r y a r t e r y p r e s s u r e d u r i n g the p e r f u s i o n m a y not e x c e e d 2 0 - 2 5 m m . / H g at t h e t i m e t h e p u l m o n a r y e d e m a d e v e l o p s . C e r e b r a l d a m a g e has b e e n n o t e d b y Bjork sJ a n d t h e s a m e t~fpe o f d a m a g e has also b e e n e x p e r i e n c e d b y o t h e r s u r g e o n s u s i n g this t e c h nic. As m e n t i o n e d a b o v e , it m a y b e d u e to i n t r a w ~ s c u l a r a g g r e g a t i o n of p l a t e l e t s a n d w h i t e cells r e s u l t i n g in m i c r o - i n f a r c t s . S e v e r a l h u n d r e d s of p a t i e n t s h a v e n o w b e e n o p e r a t e d o n u s i n g this t e c h n i q u e in E u r o p e , E n g l a n d , a n d t h e U n i t e d States. M a n y of t h e s e p a t i e n t s h a v e b e e n s e v e r e risks a n d t h e r e f o r e i n e v i t a b l y t h e m o r t a l i t y r a t e h a s b e e n h i g h , b u t not e x c e s s i v e l y so. A w i d e v a r i e t y of lesions h a s b e e n a t t a c k e d a n d t h e te(han i e h a s p a r t i c u l a r m e r i t in t h o s e o p e r a t i o n s w h e r e d e t a i l e d , m e t i c u l o u s s u t u r i n g is r e q u i r e d t r a d e r e n t i r e l y m o t i o n l e s s , b l o o d l e s s c o n d i t i o n s , s u c h as for t h e r e o a i r a n d r e c o n s t r u c H o n of a o r t i c valves. ~s TrlE USE OF

H Y P O T ] t E R S ' I I A 1~'O11 T I l E ] N D U C I ' I O N O F C A R D I A C ARREST

C r e ~ t m u s t go to M e l r o s e ~'~" for i n t r o d u c i n g t h e c o n c e p t o f i n d u c e d c a r d i a c a r r e s t u s i n g p o t a s s i m n c i t r a t e p e r f u s i o n o f t h e c o r o n a r y arteries. T h i s m e t h o d d e m o n s t r a t e d that t h e h e a r t c o u l d b e s t o p p e d , o p e r a t e d u p o n , a n d r e s t a r t e d a g a i n . H o w e v e r , it has s i n c e b e e n s h o w n t h a t p o t a s s i u m d a m a g e s t h e m y o c~ardium2 "° F o c a l n e c r o s i s a n d fibrosis m a y r e s u l t wifla ' t h e d e v e l o p m e n t of h e a r t f a i l u r e s o m e w e e k s or m o n t h s p o s t o p e r a t i v e l y . M o r e o v e r , t h e a b i l i t y o f t h e h e a r t to p e r f o r m w o r k i m m e d i a t e l y a f t e r t h e p e r i o d of c a r d i a c a r r e s t is s e r i o u s l y i m p a i r e d . TM O t h e r p h a r m a c o l o g i c m e t h o d s o f i n d u c i n g c a r d i a c ~urrest s i m i l a r l y r e d u c e t h e a b i l i t y o f t h e v e n t r i c l e s to p e r f o r m w o r k in t h e i m mediate post-operative phase. However, the induction of cardiac arrest by hypothe~ia w h i l e still d i m i n i s h i n g t h e h e a r t s c a p a b i l i t i e s does n o t r e s u l t in s u c h a s e r i o u s d e t e r i o r a t i o n in c a r d i a c f u n c t i o n . T h e r e f o r e , c o l d a r r e s t o i t h e h e a r t is p r o b a b l y t h e t e c h n i c of c h o i c e at t h e p r e s e n t time. T h e t e m p e r a t u r e o f t h e h e a r t h a s to Im r e d u c e d to a b o u t 1 5 - 1 7 C, b e f o r e it vcill stop. T h i s c a n b e d o n e b y p e r f u s i o n of t h e c o r o n a r y a r t e r i e s w i t h c o l d

CURRENT S'I~,TUS OF llYPO'rHEIll~IA

~5]

blood f r o m t h e p u m p - o x y g e n a t o r , by p e r f u s i o n of t h e coronaries w i t h cold o x y g e n a t e d blood from a s e p a r a t e circuit, or b y s u r r o u n d i n g t h e h e a r t with frozen R i n g e r ' s solu~on, a n d t h e r a p i d i n d u c t i o n of local d e e p h)q~othelmia. At t h e s a m e time, t h e c o r o n a r y arteries m a y be p e r f u s e d b y a m i x t u r e of cold b l o o d a n d R i n g e r ' s solution so t h a t cooling of t h e myocarditu-n doe~ n o t dep e n d e n ~ e l y u p o n h e a t loss at t h e e p i c a r d i a l s u r f a c e . I n spite of t h e p r 0 t e e t i o n a f f o r d e d to flae m y o c a r d i u n q b y cold arrest, it is p r o b a b l y a d v i s a b l e to m a i n t a i n s o m e p e r f u s i o n of t h e c o r o n a r y arteries w h i l e the h e a r t is arrested. T h i s is p a r t i c u l a r l y t r u e in l a r g e h y p e r t r o p h i e d hearts s u c h as a r e f o u n d in severe

r e l u c t a n c e to r e s t a r t a f t e r a p e r i o d of arrest. T h u s it is e s s e n ~ Hlat tlley should b e afforded e v e r y p r o t e c t i o n d,dring t h e p e r i o d of arrest, a n d s u c h protection is p r o b a b l y b e s t afforded b y c a n n u l a t i o n a n d p e d u s i o n o~ the c o r o n a r y artelJes w i t h 2(>9-350 cc. of b l o o d p e r minut~ arrest. A t t h e s a m e time. it is m o s t i m p o r t a n t t h a t n o n e h e a r t s h o u l d b e a l l o w e d to d i l a t e and, therefore, a p p r o p r i a t e c a n n u l a e s h o u l d b e i n s e r t e d into t h e left a n d right sides of t h e h e a r t at t h e s t a r t of t h e p r o c e d u r e w h i l e t h e h e a r t is still b e a t i n g so t h a t u n d e r no c i r c u m s t a n c e s will d i l a t a t i o n of t h e h e a r t o c c u r while it is a r r e s t e d . E v e n m o m e n t a r y d i l a t a ~ o n of a v e n t r i c l e m a y r e s u l t in i r r e p a r a b l e d a m a g e , i n a b i l i t y to restart, a n d t h e deaOa of t h e p a tient. CONCLUSIONS

V¢itbdn t h e s h o r t s p a c e of e l e v e n y e a r s t h e t e c h n i c o f ofl~ermia has e v o l v e d f r o m a n exciting, b u t t e n t a t i v e , c o n c e p t into a w i d e l y a c c e p t e d , useful, a n d safe m o d a l i t y . Its uses h a v e n e i t h e r b e e n e x h a u s t e d nor f u l l y explored. In t h e field of c a r d i o v a s c u l a r s u r g e r y t h e use of h y p o t h e r m i a a l o n e w i t h o u t t h e a d d i t i o n a l use of extracorDoreal circulation is a s a t i s f a c t o r y m e t h o d for t h e surgicoJ t h e r a p y Of s e c u n d u m atrial septal defects, T r i l o g y of Fallot, isol~tted p u l m o n a r y s t e n o s i s b o t h v a l v u l a r a n d i n f u n d i b u l a r , c o n g e n i t a l a e r i e sten0sis a n d a o r t o p u I m o n a D - w i n d o w , I t is a v a l u a b l e a d j u n c t to m a j o r c a r d i o v a s c u l a r s u r g e r y of otlner G ~ e s and flais a s p e c t of its use d e s e r v e s w i d e r a t t e n ~ o n ; T h e i n d u c t i o n of m o d e r a t e hyT~othermia r e q u i r e s o n l y e q u i p m e n t a v a i l a b l e in a l m o s t a n y h o s p i t a l a n d is, therefore, r e a d i l y a p p l i c a b l e on a w i d e s p r e a d

possible, b u t n a r r o w s t h e t o p o g r a p h i c a l a p p l i c a b i l i t y to l a r g e r c e n t e r s w i t h s u b s t a n t i a l financial under÷.,ri~ng, g o o d b l o o d b a n k i n g facilities a n d extensive staff. T h e r e f o r e , it w o u l d s e e m t h a t tile s m a l l e r c e n t e r s s h o u l d b e e n c o u r a g e d to d e v e l o p t h e s i m p l e r technics o f m o d e r a t e o t h e ~ n i a . H o w e v e r , no c e n t e r s h o u l d e m b a r k on this t ~ e o f s u r g e r y unless a d e q u a t e d i a g n o s t i c facilities a r e r e a d i l y available. A p e r i o d o f total inflow occlusion is n o t t h e time to m a k e t h e diagnosis, M o d e r a t e h y p o t h e r m i a a p p e a r s to offer definite a d v a n t a g e s in m a n y c i r c u m s t a n c e s w h e n c o m b i n e d w i t h e x ~ a c o ~ o r e a l ~ r cula~on. ~ l e p o t e n ~ a l i t i e s of d e e p h y p o t h e r m i a h a v e n o t y e t b e e n fully e v a l u a t e d ,

~52

SWAt'4 A N D P A T E N

It appears that patients can be cooled to 10-15 C. and subjected to complete cessation of respiration and circulation for prolonged periods with an acceptable mortality. However, the mere ability to re£rigerate patients does not, by itsell:, j u s t i f y t h e u s e o f t h i s m e t h o d unless it can be shown that dis~nct advantages accrue from this modality which are un'obtainable by other means. S u c h a d v a n t a g e s a s t2qe i m m o b i l i t y a n d b l o o d l e s s n e s s o f t h e o p e r a t i v e f i e l d a r e a l r e a d y a p p a r e n t a n d , ~¢or t h i s r e a s o n a l o n e , d e e p h y p o t h e r m i a already has a place in the cardiac surgeon's a~amentarium. lr~FERENCES 12. Lewis, F. J., a n d Taufic, R.I.: Closure of 1. T a l b o t t , J. H.: P h y s i o l o g i c a n d tlxeratrial septal d e f e c t s w i t h aid of h y p o a p e u t i e effects o f h y p o t h e r m i a . N e w therniia. E x p e r i m e n t a l a c c o m p l i s h E n g l a n d J. M e d . 2PA:281, 194l. m e n t s a n d r e p o r t of o n e successful 2. Swan. t-I.: T h e c u r r e n t status o f h y p o themnia. A . M . A . A r c h . Surg. 69:597, ease. S 33: 52, 1953. 13. S w a n , H., Zeavin, I., Blount, S. G., Jr., 1954. a n d Virtue, R. ~.AC: S u r g e l ~ b y d i r e c t 3. Oollan, F.: C a r d i a c arrest o f o n e h o u r "vision in t h e o p e n h e a r t d u r i n g h y p o d u r a t i o n in dogs d u r i n g h y p o t h e r m i a t h e r m i a . J.A.M.A. 153:1081, 195.3. of O ° -C. ~Collowed b y s u r v i v a l F e d . 14. Niazi, S. A., a n d Lewis, F. J.: TolerP r e c . 13:57, 1954. a n c e o f a d u l t rats to p r o f o u n d ~ y p o 4. Niazi, S. A., a n d Lewis, F. J.: Res~ampthermia and simultaneous cardiac t i o n o f h e a r t b e a t in dogs a f t e r s t a n d standstill- S u r g e r y 36:25, ] 954. stall at low t e m p e r a t u r e s . Surg. F o r 15. Simpson. S.: T e m p e r a t u r e r a n g e i n t h e ura 5:113, 1954. m o n k e y in e t h e r anesthesia. ~. ~Phys5. Smith, A. ILL: Viability o f s u p e r c o o l e d iol., L o n d o n 28:38, 1902. a n d £rozt-:n m a m m a l s . Ann. N e w 16. L o w e n h a r d t . D.: U e b e r E i n e F o r m Von York Acad. Sc. 8 0 : 2 9 1 - 3 0 0 , 1959. M a n i c M i t q~ef-er T e m p c r a t u r - S e n 6. A d a m s , F.: T h e G e n u i n e "x~rorks of k u n g . Allg. Ztschr. L Psychiat. 25: I-rJppocrat~. N e w York, W i l l i a m 685, 1868. "vVoods a n d Co., 1886. 17. A l e x a n d e r . L.: T h e t r e a t m e n t o f shock 7. C a r r i e , J.: h~edieal Reports o n t h e E f from p r o l o n g e d e x p o s u r e to cold, fects o f W a t e r , Cold, a n d W a r m . as especially in w a t e r . L o n d o n C o m a R e m e d y in F e v e r a n d O t h e r Disb i n e d Intell. Object. S u b e o m . 1945 eases, "~Vhether A p p l i e d to t h e Sur( F o r m s file No. XXVI-37, I t e m No. f a c e o f t h e B o d y or U s e d I n t e r n a l l y . 2 4 , C I O S report, London). Liverpool, E n g l a n d , F i r s t E d i t i o n , 18. L a u f m a n , H . : P r o found accidental 1797. l~ypothen~]ia. J .A.Ri.A. ] 47:1201, 8. Hunter, J.: E x p e r i m e n t s a n d o b s e r v a 1951. tions on animals, w i t h r e s p e c t to t h e 19. l~)ill, D. B., a n d Forbes, Vv'. I L : Respirp o w e r of p r o d u c i n g h e a t . I n Oba t o r y a n d m e t a b o l i c effects o f h y p o servations on C e r t a i n l~arts o f t h e thermAm Am. J. PhysioL 132:685, Animal O e c o n o m y . L o n d o n , 1786. 1941. 9. XValther, A.: B e i t r a g e Z u r Lebzre y o n 20. A d o l p h , E . F.: O x y g e n c o n s u m p t i o n s T h i e r s e h e n "~Vaxwne. Virchows Arch. o f h y p o t h e r m i e rats a n d acclimatizaF. P a t h . Anat. ~ : 4 1 4 , 1862. tion to cold. Am. J. P1wsioL 161: 10. Smith, L. ~V., a n d F a y , T.: O b s e r v a tions o n h u m a n beings w i t h c a n c e r 359, 1950. 21. H e g n a u c r , A. H., a n d D ' A m a t o , H.: maintained at reduced temperatures Oxygen consumption and cardiac of 7 5 - 9 0 F. Am. J. Clin. PatJL 10:1, o u t p u t in t h e h y p o t h e r m i c dog. Am. 1940. J. Physiol. 178:138. 1954. 1I. BigeIow, ~V. O., C a l l a g h a n , J. C., and 22. G o r d o n , A. S., Jones, J. C., L u d d i n g H o p p s , J. A.: G e n e r a l h y p o t h e r m i a ton, L. G., a n d M e y e r , B. -',V.: D e e p for e x p e r i m e n t a l i n t r a e a r d i a c s u r g e r y . h y p o t h e r m i a for i n t r a c a r d i a e s u r g e r y : Ann. Surg. 1 3 2 : 5 3 1 , 1950.

CUI~II_EN'I~

STATUS OF HYPOTHER~¢ILA

experimental and clinical use without an oxygenator. Am. J. Surg. 100:

~53

hypothermia induced b y perfusion of the entire body. Surg. Forum ii: 190. 1960. 24. Brown, X¥., and Hill. A. V.: The oxygen dissociation curve of blood and

gical Assoc:, F l o ~ d a , i961~ 35. H e g n a u e r i H ' Shriber; W. J:; a n d I-h~teriusi H . Cardiovascuiar re, Sp0nse,~Of the dog t o immersion hypo: thenniai A m i J . 4551 1950, 36. l?eur0d~ K. E~, and F l y n n ; J;: : Cardiac oxygena during se,¢6re liypo~ therinia in d0gs: Ant.: J)Pli~sidL 164~ 79, 1951' 37.

25. Rosenhain, F. tL, Penrod, K. E., and

38. Ft.,

9~3. Kameya, S., Oz, M., Neville, V¢. E . ,

hypothermic d o g . Am. J. Physiol. 26. Edwards, XV. S., Simmons, E., Lorebardo, C. R., Bennett, A.. and Bing, R. J.: Coronary blood flow in hypothermia. A.M.A. Arch. Surg. 71:853, 1955. 27. Gollan, F., Hot,man, J. E., and Jones. R. M.: Maintenance of life of dogs below 10 C. without hemoglobin. Am. J. PhysioL 179:640, 1954. 28. ltosenthal, T. B.: Effect of temperature on the p H of blood and plasma in vitro: J. Biol. Chem. 173:25, 1948. 29. Trede, M., Foote, A. V., and Maloney, J. V., Jr.: Pathophysiologie aspects of deep h:~othermia with extracorl~real circulation. In press. 30. Brewin, E. G., Gould, It. P., Nashat, F. S., and Nell, E.: An investigation of proMems of acid base equilibriuna in hy-pothermia. Guy's Hosp. Reports 104:177, 1955. 31. Ve'addell. V¢. G., Faidey, H. B., a n d Bi XV. G.: Improved managemerit of clinical hypothermia. Ann.

39.

40.

41.

42.

43. 32. Fairley, H. B., \Vaddell. '~V. G., and Bigelow, ~¢V. G.: Hypothermia for cardiovascular surgery. A~dosis in the rewarming period. Brit. J. Anaesth. 29:310, 1957. 33. Gordon, A. S., hieyer, B. V¢., and Jones, J. C.: Open heart surgery using deep hypothermia without an oxygenator. J. Thorac. & Cardiovase. Snrg. 40:787, 1960. 34. Ballinger, V¢. F.. VoUeweider, H., Templeton, J. Y., Pierueei. L.: The acidosis of hypothermia. Anl. Stir-

44.

45.

uation of prolonged+ IwpOthennia. A, ~I, 1955. \Vyn ~rbance~s asSociateciI w i t h failure to metaboliSe glucose during liypothennia, LanCet, 2: 575, 19542 Elliott; H ~ W~; and: Crismon, Increased sensitivity Of b y p o t l l e ~ i c rat~s to injected potassium and the in: fluence o f calcium; dig i7 cost on survival Am~ J. . .: 366, 1947: McMillan, I : K, . . R;, . .M . e. l r. o s e , D ClmrehilliDavidson~ H~ C . ; and L~n, R: Hypothernlia: s o m e obsercations on b l o o d gas and d e e trolyte changes d u r i n g s u r f a c e cooling. Ann, Roy. CoIL S n r g ; England 16:186, 1955, Fabian, L: ~V:~ Stainton, R;; Harra, M.; Lifig; P : C;i a n d s h a r e r , W:: Ct~6mophysiologic alterations during hyl)othermia~ ganglioplegia a n d in~ tracardiae surgery; Anestl~e*sia & Analgesia 34:214, 1955. Fleming, R . : Acid base balance of fl~e blood dogs a t r e d u c 6 d body temperature: .... A : M , A Arch, Surg: 68: 145, 1954: I-Iarnilton, J B., Dresbach, M:, and Hamilton, R. S.: Cardiac changes during progressive liypotlmrmia' Arm J, PhysioL 118:71, 1937. Blair, E., A u s t i n , R: R:, B l o n n t , S. Gilbert, Jr~; and S w a n ; H:: A study of the cardiovascular changes during cooling and r e w a k i n g .*n human subjects xmdergoing total circulatory oedusiofi, J' Thorae. Snrg. ~ : 7 ~ ,

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1957. 46. Lofstrom, B.: I n d u c e d h y p o t h e r m i a a n d i n t r a v a s e u l a r a g g r e g a t i o n . Acta. Anaest. Scand. Supp. 3:1--I9, 1959. 47. Gelin, L. E., and L o f s t r o m , B.: A pre,l i m i n a r y s t u d y on p e r i p h e r a l circulation d u r i n g d e e p h y p o t h e r m i a . Acta. Chir. S c a n d i n a v . 108:402, 1955. 48. L o n g , D. M., S a n c h e z , I .... Varco, R. L., a n d L i l l e h e i , C. ~V.: Use of p l a s m a e x p a n d e r s in e_xtraeorporeal circulation. Soe. o f Univ. Surgeons, Kansas City-, 196]. 49. F u h r m a n , G. J., F u h r m a n , F. A., a n d F i e l d , J . : M e t a b o l i s m o f r a t hem~t slices w i t h special r e f e r e n c e to effects o f t e r n p e r a t u r e a n d anoxia. Am. J. Physiol. 163:642, 1950.

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~o55

neous a n d surgically i n d u c e d h y p o a t o r . Ji T b o r a c . & Cardiovasc: Surg. t h e r m i e ventricular ~brillation. Ann. 40:~7, 1960. '9 N e w York Acad. Sc. 8 0 : 3 5 I , 1,9,59. 71. J o h n s o n , P., LeSagc, A., Floyd, M. D., Young, V¢'. G., a n d Scaly, ~ r C.: Prevention of ventrieular fibrillation d u r i n g p r o f o u n d h y p o t h e r m i a by quinidine. Ann. Surg. 151:490, 1960. 83, Virtue; R o b e r t VV:: H v p o f l a e ~ i e 79. Niazi, S.. and Lewis, F. J.: T h e effect of carbon dioxide on h e a r t block a n d c Tl mas: :195a ventricular fibrillation d u r i n g h y p o 84. E ; G~: d u r i n g : hythermia in rats a n d dogs. Surg. Foru m 5:106, 1954. 73. C a r a n n a . L. J.. Telmosse, J. P., a n d Swan, H.: Effect of i n ~ a v e n o u s nutrient solutions on ventricular fibrillation in tlle h y p o t h e n n i c dog. A.M. M c d , 42:537, 1939. A. Arch. Surg. 76:394, 1958. 86: F u l l r m a ~ ; F, and Mar74. S h n m w a y , N. E.. G l i e d m a n , H. L.. a n d tin~ A' W ~ : E f f ~ t s o f t e m p e r a t u r e Lewis, Iv. J.: C o r o n a r y perfnsion for on the of brain longer periods of cardiac o c c l u s i o n u n d e r h y p o t h e r m i a . J. Thorac. Surg, 87, StonC : H ; 30:598, 1955. ese: 75. Riberi, A., Siderys, H., a n d S h u m a c k e r , on th c e r e b r a l H. B., Jr.: Ventrienlar ffl)rillation in t h e h y p o t h e r m i c state. I. Prevention by sino-auricular n o d e blockade. 1956:. Ann. Surg. 143:216, 1956. 8 8 . LOugheed; V¢~ h~Ig: a n d K a h n ; D : S : ~ 76. Parkins. XV. R'I., Jensen, J. M,, a n d Circumv6ntiofi o f ahoxia d u r i n g ~ Vats, H. M.: Brain cooling in t h e rest o f Cerebral circulation ~'or intra, prevention of brain d a m a g e d u r i n g periods of circulatory occlusion in 9.26, 955. dogs. Ann. Surg. 140:284, 1954. 89. P o n t i u s , R , G.; Bt0odwell, R. O.i C o o l ' 77. A d a m s , J. E., a n d P e v e h o u s e . B." C.: Regional h y p o t h e r m i a of t h e brain. Clin. N e u r o s u r g . 6 : 1 0 4 - 1 8 , 1958. 78. Niazi, S. A.. a n d Lewis, F. J.: P r o f o u n d h y p o t h e n n i a in tl~e dog. Snrg. G y m & Obst. 102:98, 1956. W :B: S a u n d e r s & Co:~ p i ~ 2 ~ , 1 9 ~ i 79. Sano, M. E.. a n d Smith, L. \V.: Critical 90, OwenS; c,; E, histopathologicaI study of fifty postS w a n , H ' i ProlOnged experimental m o r t e m patients with c a n c e r subj e c t e d to local or g e n e r a l i z e d refrighyp0thermia~ A~M.A, Arch~ Surg:: 70: eration o o m p a r e d to a similar control 9 5 , 1955, g r o u p of flliriy-seven non-refrigerated 9 I . Rosomoff, H~ L ; S h u l m a n , i-L, Raynor, patients. J. Lab. & Clin. Med. 26: R , a n d ~romger, ~V,: E x p e r i m e n t a l 443. 1940. brain and d e l a y e d h ) ~ o 80. Stephens, J., a n d Appleby, S.: Polythermia, S u r g . Oyn: Obst; I I 1 : 2 7 ; n e u r o p a t h y following i n d u c e d h y p o 1960. tbermia. Tr. Am. Neurol. Assoc. 80: 92. \ V i l l a i n s , R. G:, a n d Spencer, F , C.: 102, 1955. T h e clinical u s e oOf h ~ o t h e m a ~ £oi, 81. Biork, V. O.: A n effective blood h e a t e x c h a n g e r for d e e p h y p o t h e r m i a in 148:462, 1958, assoeiation w i t h extracor~oreaI cir93. KhaliL Hi H.: Effects o f h : ~ o t h e r m i a culation b u t ~ e l u d i n g t h e on CnC h y p o ~ a | a m i c * p i t n i t a r ] re-

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sponse to stress. Brit. M. J. 2:733, 107. Zindler, M.: Die K u n s d i c h e t t ~ o 1954. t h e r m i e in d e r Praktischen Chirurgie. 94. Egdahl, R. H . , Nelson0 D. tt., a n d Arch2 Klill. Clair. 2 8 4 : 2 i 2 , 1956. H u m e , D M:: A d r e n a l cortical 'func108 Sellick, B. A . : A m e t h o d of h y p o t h e r tion in hy-pothermia. Surg. G y n . a n d mia for o p e n h e a r t surgery. L a n c e t i : 4 4 3 , i957. Obst. 101:715, 1955. 95. S w a n , It., Jenkins, D., a n d Helmreieh, 109. Wilson, J. N., MarstmlI, S. B., Beresford, M. L.: T h e a d r e n a l cortical r e s p o n s e V., M o n t g o m e ~ , V., Jenkins, D., to surgery: III. C h a n g e s in plasma and Swan, H.: E x p e r i m e n t a l h e r e o f a n d u N n a r y corticosteroid levels durr h a g e : t h e deleterious effect of h y ing h y p o t h e n n i a in m a n . S u r g e r y p o t h e r m i a on s u ~ i v a l a n d a c o m p a r 412:202, 1957. ative evaluation of plasma volume 96, Page, L., KnpsLnel, H., a n d Adams, J.: changes. Ann. S n r g . 144:696, 1956. Effect of h y p o t h e r m i a o n renal f u n c 110_ McQl~iston, "~V. O.: Anaesthesia in cart i o n . . ~ a y Med. Reseaa-eh L a b . Rediac surgery. A.M.A. Arch. Surg. p o r t # 1 5 2 , O c t o b e r 22, 1954. 61:892, 1950. 97. n, H.: 1 I I . Lewis, F. J., Pdng, D . M., a n d Alden, renal J. F.: A t e c h n i q u e for total b o d y c i r c u l a t i o n of t h e dog. Anaesthesiolcooling o f the febrile, g r a v e l y ill o g y 16:230, 1955. patients. S u r g e r y 40:465, [956. 98. Segar, V¢. E., Riley, P. A., Jr., mad 112. Blades, B., a n d Pierpont, H. C.: A Barila, T_ G.: U r i n a r y composition simple m e t h o d for i n d u c i n g h y p o d u r i n g h y p o t h e r m i a . A m . J. Physiol. thermia. Ann. Surg. 140:557, i954. 185:528, 1956. 113. Eiclma, L. VVL: T h e r m a l gradients d~tr.t/9. M o r a l e s , P., C a d ) c r y , V¢., Morello, A., ing v a r y i n g b o d y t e m p e r a t u r e s . Arch. a n d M o r M ~ , G.: Alterations in renM Plays. M e d . 29:687, 1948. function d n r i n g hypoflaennia in m a n . 114. V e r m e u l e n - C r a n c h , D. M. E., a n d Ann. Surg. 145:488, 1957. Spi , J.: A T e m p e r a t u r e conI00. B e r n h a r d , \V. F., Cahfll, G. F., Jr., trolled c~binet o p e r a t i n g table for a n d Curtis, G. ~¢V.: T h e rationale o f safe h y p o t h e n n i a . Brit. J. Anaesth. s u r g e r y u n d e r h y p o t h e r m i a in cer29:400, 1957. tain patients with severe hepatocel115. B o e r c m a , L, XVildschut, A., Schmidt, lular disease. A n n . Sur~. 145:289, XV. J. H., a n d Broekhuysen, L.: Ex1957. pel_mental researches into h y p o IOI. MoeJre. F. 1).: Personal c ~ m m n n i c a t i o n , t h e r m i a as an aid in t h e s of 1960. the heart. Arch. C h h~. Neerl. 3:P9~5, 10~9. B u n k e r , J. P., a n d Goldstcin, R.: Coag1951. ulation dnNn g h y p o t h e r m i a in m a n . 116. Delomae, E. J.: E x p e r i m e n t a l cooling Proc. Soe. Exper. Biol. 97:199, 1958. o f the bleod stream. L a n c e t 2:914. 103. Von Kaulla, K. N., a n d Swan, H.: Clot1952". ting deviations in m a n associated 117. Gollan, F., Bloc, P.~ a n d S c h u m a n , H.: with o p e n - h e a r t s u r g e r y d u r i n g h y p o Exclusion o f the h e a r t a n d lungs f r o m thermia. J. ~ a o r a c . Surg. 36:85"7, circnlation in the hyTpothermic, 1958. closed-chest dog b y m e a n s of a 104. Swan, It., Virtue, R., Blount, S. G., p u m p - o x y g e n a t o r . J. Appl. Physiol. Jr., a n d Kircher, L . J . : lermia 5:380, 1952. in surgery, analysis of 100 eli:~i¢-,'d 118. Pierce, E. C., III, a n d Polley, V. B.: cases. Ann. S~_trg. 142:382, 1955. D tial h y p o t h e n n i a for intra105. Bigelow, ~V. G.: O p e r a t i o n a n d h y p o c a r d i a c surgery: p r e l i m i n a r y report them~ia. Bldl. Soc. Internat. Chfr. of a p u m p - o x y g e n a t o r incorporath~g 14:308, 1955. a h e a t e x c h a n g e r . A.M.A. Arch. Surg. I06, Brom, A. G.. a n d Kalsbc~ek, H.: D i e 67:521, 1953. C h l r u r g i s c h e B e h a n d h m g d e r Pul119. Brock, R., a n d Ross, D. N.: H y p o monal Stenose. T h o r a x Chlinlrgie 7: t h e r m i a p a r t III: T h e clinic-a/ ap229, 1957. plication o f h y p o t h e n u i c techniques.

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~57

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1 3 -0. El:

133. F (

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Swan, M.D., Clinical Professor of Surgery, Ur, of Colorado School of Medicine, Denver. Colo. Bruce C. Paten, M.D., Director of HaL~ted Laboratory [or l~xperimental Surgery, University of Colorado School of Medicine, Denver, Colo.