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C l i n i c a l a p p l i c a t i o n s o f c a r b o n d i o x i d e / d i g i t a ls u b t r a c t i o n a r t e r i o g r a p h yF r e d A . W e a v e r , M D , M i c h a e l J . P e n te c o s t , M D , A l b e r t E . Y e ll in , M D ,S t ev e n D a v i s, M D , E t h e l F i n c k , M _ D, a n d G e o r g e T e i t e lb a u m , M D , L os A nge l es , Ca l i f .D u r i n g a n 1 8 - m o n t h p e r i o d 3 3 p a t i e n t s i n w h o m t h e r e w e r e c o n t r a in d i c a t io n s t o t h e u seo f i o d i n a t e d c o n t r a s t a r t e r i o g r a p h y u n d e r w e n t 4 0 c a r b o n d i o x i d e / d i g i t a l su b t r a c t i o na r t e r iogram s for l ow er ex t rem i ty i schemia (19) , seve re hy per t ens ion an d rena l i nsuf f i-c i ency (12) , o r a r t e r i a l aneurysm (2) . Cont ra ind ica t ions to iod ina ted cont ra s t agen t sinc luded rena l i nsuf f ic i ency , conges t ive hea r t f a i lu re , an d cont ra s t hy persens i t i v ity . S ix-t een aor t i c , 15 i l iac - femora l -popl it ea l -t i b i al , fi ve aor t a - i l i ac - femora l and fou r aor t a -q i ac .femora l -popl i t ea l - t ib i a l ca rbon d iox id e /d ig i t a l sub t rac t ion a r t e r iog raphy s tud ies were pe r -form ed. In 11 s tud ies , imag ing of se l ec ted a r t e r i a l segmen t s requi red the a ddi t ion o f 10t o 6 0 m l o f d i l u te n o n i o n i c c o n t r a s t. G u i d e d b y c a r b o n d i o x i d e / d i g i ta l su b t ra c t i o n a r -t e r iography s tud ies four femora l - t i b i a l bypasses , t h ree aneurysmorrhaphies , two anr to-rena l bypasses , one aor tofe mo ra l bypass and o ne fem ora l - femo ra l bypass were successfu l lyp e r f o r m e d i n 1 1 p a t i e n ts . I n a d d i t i o n , c ar b o n d i o x i d e / d i g i t a l su b t r a c t io n a r t e r i o g r a p h ydi rec t ed angiop las t i e s o f t he com mo n i l iac (4) , supe r fi c ia l femo ra l (6 ) , popl i t ea l (3 ) , o rt i b io p e r o n e a l t r t m k ( 1) w e r e p e r f o r m e d i n 1 0 p a t i en t s . C o m p l i c at i o n s o f c a r b o n d i o x -i d e / d i g i t a l su b t r a c t io n a r t e r i o g r a p h y i n c l u d e d t r a n s i e n t d e t e r i o r a ti o n i n r e n a l f u n c t i o ni n t h r e e p a t i e n ts i n w h o m 2 0 m l o f n o n i o n i c c o n t r a s t w a s u se d , a n o n f a t a l m y o c a r d i a lin fa rc t ion a f t e r a popl i t ea l pe rcu taneous t rans lum ina l ang iop las ty in one pa t i en t , a ndt r a n s i e n t t a c h y p n e a a n d t a c h y c a rd i a d u r i n g a c a r b o n d i o x i d e / d i g i ta l su b t r a c t io n a r t er i -o g r a p h y s t u d y i n o n e p a t i e n t . D i a g n o s t i c a rt e r io g r a m s a r e o b t a i n ab l e u s i n g c a r b o n d i o x i d ea s t h e c o n t r a s t a g e n t . C a r b o n d i o x i d e / d i g i ta l su b t r a c ti o n a r t e r i o g r a p h y p e r m i t s p a t i e n t swi th sym ptom at i c a r t e r i a l d isease a t h igh r i sk fo r con t ra s t r e l a t ed compl i ca t ions to sa fe lyu n d e r g o a r t e r i o g r a p h y a n d su b se q u e n t a r t e r ia l r e c o n s t r u c t io n o r e n d o v a sc u l a r in t e rv e n -t i o n . ( J V A se S U R G 1 9 9 1 ; 1 3 : 2 6 6 - 7 3 . )

A d v a n c e s i n v a sc u l a r su r g e r y h a v e e x p a n d e d t h ei n d i c a t i o n s f o r o p e r a t i v e a n d e n d o v a sc u l a r i n t e r v e n -t i o n t o a n e l d e r ly p a ti e n t p o p u l a t i o n t h a t f r e q u e n t l yhas coexi s t ing rena l , ca rd i ac , o r o the r medica l i l l -nesses . Surg ica l morb id i ty has , i n pa ra l l e l , been dra -m a t i ca l ly r e d u c e d b y i n n o v a t i o n s i n m o d e r n a n es -t h e s i a a n d c r i t i c a l c a r e , t h u s p e r m i t t i n g c o m p l e xi n t e r v e n t i o n s t o b e s a f e ly p e r f o r m e d i n t h e se c o m -p r o m i s e d p a t i e n t s . H o w e v e r , t h e n e p h r o t o x i c i t y ,h i g h o sm o l a t i t y , a n d a l l e r g i c p o t e n t i a l o f p r e se n t l ya v a i l a b l e i n t r a v a sc u l a r c o n t r a s t a g e n t s r e m a i n s s i g -n i fi c an t , a n d t h u s f o r m a n y p a t i e n ts t h e p e r f o r m a n c eo f p r e o p e r a t iv e a r t e r io g r a p h y n o w r e p re s e n ts t h e

From the Departments of Su rgery and R adiology,Universityo fSouthern C aliforniaSchool of Medicine, and the Los AngelesCoun ty, and Universityof Southern CaliforniaMedical Center(Dr. Weaver), Los Angeles.Presented at the Forty-fourxhAnnual Meeting of the Society orVascular Surgery, Los A ngeles, Calif.,June 4-6, 1990.Reprint requests: Fre d A. W eaver, MD , Department of Surgery,LAC and U SC M edicalCenter, 1200 N. S tate St., Room 9442 ,Los A ngeles, CA 90033.24 /6 /25900

g r e a t e s t h a z a r d o f a p r o p o se d v a sc u l a r r e c o n s t r u c -t ion . 1-~ Ca rbo n d iox ide (C O2) , a nonto x ic , i n j ec t ab le ,r a p i d l y a b so r b e d g a s i s a p o t e n t i a l a l t e r n a t iv e t o s t a n -d a r d c o n t r a s t a n d m a y i n c r e ase t h e s a f e t y o f a r t e ri -o g r a p h y i n t h e p a t i e n t a t h i g h r isk . s l

C a r b o n d i o x i d e h a s s e v e r a l p r o p e r t i e s t h a t m a k ei t an a t t rac t ive a l t e rna t ive to s t anda rd agent s . I t i sn o n a l l e r g e n i c , e l i m i n a t i n g t h e p o s s i b i l i ty o f f a t a l h y -p e r se n s i t i v i t y r e a c t i o n s . I t i s n o t n e p h r o t o x i c o r h y -p e r o sm o l a r , w h i c h e l i m i n a t e s t h e n e e d f o r p r e a r t e -r i o g r a p h y h y d r a t i o n i n p a t i e n ts i n w h o m c a rd i ac a n dr e n a l d y s f u n c t i o n c o e x is t . I t c a n b e u se d f o r s e q u e n -t i a l s t u d i e s o n c o n se c u t i v e d a y s w i t h o u t i n c r e a s i n gthe r i sk of rena l fa i lu re . I t i s cos t e f fec t ive ; on e t a nko f C O 2 g a s c o s t s a p p r o x i m a t e l y 2 0 d o l l a r s , w h e r e a sn o n i o n i c c o n t r a s t c o s t s 1 d o l l a r / m l .H a w k i n s n i n 1 9 8 2 d e sc r i b e d t h e f i rs t u se o f C O za s a n a r te r i a l c o n t r a s t a g e n t . B y u se o f C O 2 a n d d i g i t a lsu b t r a c t i o n t e c h n i q u e , h i g h - q u a l i t y a r t e r i o g r a p h i ci m a g e s o f t h e a b d o m i n a l a o r t a , v i s c er a l a rt e r ie s , r e n a la r te r ie s , a n d l o w e r e x t r e m i t y a r t er i a l tr e e w e r e o b -t a in e d . T h e i ss u e o f w h e t h e r s u c h s t u d ie s w e r e o fsu f f i ci e n t q u a l i t y a n d a c c u r a c y t o g u i d e t h e m a n a g e -

2 6 6

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V o l u m e 1 3N u m b e r 2F e b r u a r y 1 9 9 1 Appl ica t ion o f carbon d ioxide~d ig i ta l sub tract ion arter iography 2 6 7

m e n t o f p a t ie n t s w i t h a r t e r ia l d i s e as e w a s n o t a d -d ressed .D u r i n g t h e p a s t 1 8 m o n t h s C O 2 / d i g i t a l s u b t r a c -t i o n a r t e r i o g ra p h y (C O 2 / D S A ) h a s b e e n u s e d a t o u rins t i tu t ion t o as sess the ex ten t and pa t te rn o f a r te r i a ld i sease in a se lec t g ro up o f pa t i en t s a t h igh r isk .S u b s e q u e n t a r te r ia l r e c o n s t ru c t i o n , e n d o v a s c u l a r i n-t e rv e n t i o n , o r n o n o p e ra t i v e m a n a g e m e n t w a s b a s e dso le ly on these d iagnos t ic s tud ies . Fr om th i s expe-r ience spec i f i c in fo rmat ion concern ing the d iagnos t icv a l ue , li m i t a ti o n s , a n d c o m p l i c a t io n s o f C O 2 / D S Ain the pa t i en t wi th a r te r ia l d i sease has been accrued .Th is repor t ou t l ines th i s exper ience , de ta i l s the t ech -n i ca l a sp e c ts o f C O 2 / D S A , a n d s u m m a r i z e s t h e c l in -i c a l c o n t e x t i n w h i c h w e h a v e fo u n d t h i s t e c h n i q u et o b e o f va l ue .P A T I E N T S

B e t w e e n D e c e m b e r 1 9 8 8 a n d M a y 1 9 8 9 , 3 3 p a-t i en t s h a v e u n d e rg o n e 4 0 a r t e r io g ra m s i n w h i c h C O 2gas was used as a con t ras t agen t . Seven teen pa t i en t sw e r e w o m e n ; 1 6 w e r e m e n . T h e i r m e a n a g e w a s 6 1years ( range 27 to 81 years ) . Assoc ia ted med ica l i l l -nesses inc luded rena l in su ff ic iency no t requ i r ing d i -a lys i s in 22 (67%), hyper tens ion in 18 (56%), d ia -be tes in 16 (50 % ), card iac d i sease in 13 (41 %) , cc-rcb rovascu lar d i sease in s ix (19%), and ch ron ico b s t ru c t i v e p u l m o n a ry d i s e a s e i n f i v e (1 6 % ) . D i a g -n o s t ic a r t e r i o g ra p h y w a s i n d i c a t e d fo r t h e e v a l u a t i o no f s e v e re l o w e r e x t r e m i t y i s c h e m i a m a n i f e s t e d b y r e s tp a i n , f o r e fo o t g a n g re n e , n o n h e a l i n g d i g i t al a m p u -ta t ion , o r u lcera t ion ha 19 (60%) pa t ien t s ; severehyp er tens ion and rena l in su ff ic iency in 12 (34 % );and ar te r ia l aneurysms in two (6%) pa t ien t s . Re la t ivec o n t r a i n d ic a t i o n s t o i o d i n a t c d c o n t r a s t a r t e r i o g ra p h yinc luded : e leva ted serum crea t in ine , - - -1 .7 m g/d l , in2 2 p a t i e n t s (m e a n s e ru m c re a t i n i n e = 2 .7 m g / d l ) ;conge s t ive hear t fa i lu re in 12 , con t ras t hypersens i -t iv i ty in two .M E T H O D S

A l l C O 2 / D S A p r o c e d u re s w e r e p e r f o r m e d v i a ei-ther a femora l o r ax il la ry a r te ry punctu re . W he n us inga f e m o ra l p u n c t u r e t h e u s e o f a n a n t e g ra d e o r r e t -ro g ra d e a p p ro a c h w a s d e p e n d e n t o n t h e a r te r ia l s e g-m e n t s o f in t e re s t . C a t h e t e r s , 5 t o 5 . 5 F , w e re u s e d i ne a c h p a ti e n t . F o r a b d o m i n a l a n d p e l v i c a r te r i o g ra p h ya p ig t a il c a t h e t e r w a s u s e d . A n t e g ra d c o r r e t ro g ra d es tud ies o f the fem ora l , pop l i t ea l , and t ib ia l vesse lsw e r e p e r f o r m e d w i t h a p r e s h a p e d e n d h o l e c a t h e t e ro r d i l a t o r. Im m e d i a t e l y b e fo re i n j e c t i o n t h e c a t h e t e ra n d a t t a c h e d t u b i n g w e re f l u s h e d w i t h 5 t o 1 0 c c o fCO2. F i f ty cc o f CO2 gas in a p las t i c sy r inge was then

rap id ly in jec ted in t raar te ria l ly by hand befo r e imag-i n g. U p t o 1 5 , 5 0 c c i n je c t io n s o f C O 2 , s p a c e d 2minu tes apar t , were used in any s ing le s tudy . Dig i ta ls u b t r a c t i o n t e c h n o l o g y w a s t h e s o l e m e t h o d o f im -a g i n g w i t h i m a g i n g s p e e d a t 3 t o 6 e x p o s u re s / s e e .W h e n a r te r ia l s e g m e n t s w e re n o t a d e q u a t e l y vi su al -i z ed b y C O 2 / D S A a s m al l v o l u m e o f n on i o n ic c o n -t r a s t ( 1 0 t o 2 0 c c ) m i x e d 1 : 1 w i t h n o rm a l s a l i n ewas used to de l inea te the a r te r ia l ana tomy. Th is wasnecessary in 11 s tud ies. Analges ia was adm in is te redas necessary . Base l ine and pos tp rocedura l per iphera la r t e r i a l b l o o d g a s s a m p l e s w e re o b t a i n e d i n n i n estudies .

In 1 9 p a t ie n t s w i t h l o w e r e x t r e m i t y is c h e m i a t h ea r t e r i a l s e g m e n t s f o r C O 2 / D S A w e re s e l e c t e d a c -c o rd i n g t o t h e a n a t o m i c l o c a t i o n o f t h e o c c l u si v el e s i o n . Tw e n t y - t h r e e s t u d i e s w e re p e r fo rm e d i nt h e s e 1 9 p a t i e n t s , i 0 i n c o n j u n c t i o n w i t h p e r c u t a -n e o u s t r a n sl u m i n a l a n g i o p l a s t y (P TA ) . C a rb o n d i o x-i d e / d ig i ta l s u b t r a c t i o n a r t e r i o g ra p h y w a s c o n f i n e d t othe i l i ac- femora l -pop l i tea l - t ib ia l segm en ts in 15 s tud -ies , ao r ta - i l i ac- femora l segmen ts in fou r , and ao r ta -i l i ac- femora l -pop l i t ea l - t ib ia l segmen ts in fou r . Thel o w e r e x t r e m i t y w a s e l e v a t e d t o e n h a n c e t h e q u a l i t yo f t h e a r t e ri a l i m a g e b y t a k i n g a d v a n t a g e o f t h e l o w e rd e n s i t y o f C O 2 a s c o m p a re d t o b l o o d .

In 1 0 o f 1 9 p a t i e n t s w i t h l i m b i s c h e m i a , P TAd i r e c t e d b y C O 2 w a s p e r fo rm e d . B e fo re p e r fo rm i n gP TA , C O 2 w a s u s e d t o im a g e t h e a r t e ri a l s e g m e n t o fi n t e r e s t , a n d C O 2 / D S A r o a d m a p i m a g e s w e r e o b -ta ined . Di lu te non ion ic con t ras t was used to in f la tet h e a n g i o p l a s t y b a ll o o n . R e s o l u t i o n o f th e w a i s t o fthe ba l loon was obser ved f lou roscop ica lly . Successfu lP TA e n d p o i n t s i n c l u d e d f l o u ro s c o p i c r e s o l u t i o n o fthe ba l loon wais t , equa l iza t ion o f in t raarte r ia l p res -su res p rox imal and d i s ta l to the l es ion , o r repea tC O 2 / D S A d e m o n s t r a t in g a < 5 0 % r e si d ua l st en o si s.F i f t e e n st u d ie s w e re p e r fo rm e d i n i 2 p a t i en t s t oinves t iga te renovascu lar d i sease . Eleven pa t ien t s hadsevere hyper tens io n p lus rena l in su ff ic iency , and o neh a d h y p e r t e n s i o n o n l y . I n t r a a o r t i c i n j e c t io n o f C O 2was used in al l s tudies . Select ive renal artery in jec-t ions were pe r fo rm ed ha one pa t i en t . Th e i li ac andfe m o ra l a r t e r i e s w e re s t u d i e d a s w e l l b y C O 2 / D S Ai n t h r e e p a t i e n ts w i t h a n a b d o m i n a l a o r ti c a n e u ry sm ,one wi th ao r to i l i ac occ lus ive d i sease , and one wi th ar e n a l t r a ns p l an t . R e n a l a r t e ry im a g i n g b y C O 2 / D S Aw a s e n h a n c e d b y p l a c in g t h e p a t i e n t i n a p ro n e ,o b l i q u e , o r l a t e r a l d e c u b i t u s p o s i t i o n s u c h t h a t t h er e n a l a r te ry o f i n t e re s t w a s n o n d e p e n d e n t .

Th e i l iac and fem ora l a r t e ri es were s tud ie d in onepat ien t wi th a pu l sa t i l e ingu ina l mass a f te r a card iacc a t h e te r i z at i o n , a n d t h e a b d o m i n a l a o r t a w a s s t u d i e d

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2 68 We av er el= M.Journal ofVASCULARSURGERY

Fig. 1. C O 2 / D S A of the infrageniculate popliteal artery.The anterior tibial artery is occluded at its orig in. Theperoneal (P) and posterior tibial (PT) arteries are patentproximally, but contain extensive occlusive disease. Theinability of CO2/DSA to image the distal reconstitutionof the infrapopliteal arteries necessitated the use of (non-ionic) contrast.

b y CO2-DSA in a single patient with a mycotic ab-dominal aortic aneurysm involving the renal and vis-ceral arteries.R E S U L T S

The partial pressure of CO2 ( P c o 2 ) in peripheralar ter ial blood gas samples obtained after CO2/DSAwas unchanged from baseline determinations. Al-though pain from the procedure was less than thatwith ionic contrast agents, some patients did expe-r ience enough discomfort to require mild parenteral

analgesia. The C O 2/ DS A studies perform ed are sum-marized with respect to indication, location, contrastagent, and treatment in Table I .

In patients with lower extremity ischemia, all ar-ter ial segments in continuity were satisfactorily im-aged by use of on ly CO2 as the contrast agen t . H ow -ever, visualization of the arterial anatom y and col-lateral pathways distal to an occlusion or h igh-grade(>90%) stenosis was occasionally suboptimal be-cause of f ragmenta t ion of the CO2 contrast co lunmby the stenosing lesion (Fig. 1). This limitation inCO2/DSA was most p ronounced when an in f ra-popliteal ar terial segm ent w as involved by severe oc-clusive disease. This necessitated the addition of 10to 20 ml o f dilute nonionic contrast in six patients.In tw o o ther pa t ien ts severe to r tuosi ty o f the com-mon and external iliac artery resulted in poor visu-alization because of seque strati on of CO2 withinthese segments . Fo rty milliliters of dilute nonio niccontrast demonstrated tortuous i l iac vessels in bothpatients and a 50% common il iac stenosis in one.

With the diagnostic information obtained en-t i re ly f rom these CO 2/D SA studies , PTA of s teno ticor occluded arter ial segments was performed in 10patients and arter ial reconstruction in six. One ofthese patients underwent both a PTA and arter ialreconstruction. Three o f the remaining patients weremanaged nonopera t ive ly , and one pa t ient underwe nta Symes amputation.Percutaneous transluminal angioplasty proce-dures involved lesions of the com mo n lilac (4) , su-perficial femoral (6), popliteal (3), and tibioperonealtrunk (1) . In seven patients the PTA was performedat the t ime o f the init ial diagnostic study. Ca rbondioxide was the only contrast agent used to guidethe angioplasty in seven patients (9 lesions) . In onepatient a PTA of a t ibioperoneal trunk stenosis wascomplicated by spasm and arter ial thrombosis. Sixtymilliliters of dilute nonio nic c ontrast, intraarterialurokinase, and nitroglycerin were required to restorepatency. On e pa tient had a successful com mo n il iacPTA guided by CO2 but required 10 ml ofnoni oniccontrast to guide angioplasty of a 3 cm occlusion ofthe superf icial femoral ar tery. One patient had a su-perficial femoral ar tery PTA guided by CO2 only, bu tpoo r visualization o f a distal popliteal lesion by CO2necessitated 10 mi of nonionic contrast for PTA.After PTA , restoration of pulses distal to the dilationoccurred in f ive patients, the ankle/brachial Dop plerindex improved in four, and no observable hemo-dynamic change was docum ented in one .Reconstructive procedures included fourfemoral- tibial bypasses, one femoral-femoral bypass,

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Volume 13Number 2February 1991 Application o f carbon dioxide/d~ital subtraction arteriography 26 9

Fig. 2. CO JD SA arteriogram demonstrates the left renal artery (R), superior mesenteric artery(S), and celiac axis (C).

Table I. CO2/DSA diagnostic and therapeutic studiesContrast Treatment

Indication Location Patients Studies C02 C02 + nonionic PT AAr temal

reconstructionLimb ischemia A-I-FI-F-P-TA-I-F-P-TRenovascular A-RA neuw s m A

FTotal

4 4 3 1 2 211 15 8 7 7 24 4 1 3 1 212 15 15 0 0 31 1 1 0 0 11 1 1 0 0 133 40 29 11 10 11

A, Aorta; F, femoral; I , iliac; P, popliteal; R, renal; T, tibial.

and one aorta-femoral bypass. In all patients under-going arterial reconstruction the CO2/DSA studycorrelated well with the intraoperative findings, al-lowing the com pletion of the planned operat ive pro-cedure. Primary graft patency of these reconstruc-t ions is 100% with a mean follow-up of 7 months(range 1 to 15 months).Renovascular disease was evaluated by 15CO2 /DSA studies in 12 patients. Carbo n dioxide wasthe only contrast agent used in these studies. Themain renal artery and proximal segmental brancheswere reliably visualized, but imaging of the intra-parenchymal arterial architecture was erratic. Proxi-mal and p rimary branch points o f the cel iac and su-perior mesenteric arteries were also well imaged(Fig. 2). An associated infrarenal abdominal aorticaneurysm was present in three patients. A lthough in

all three the proximal port ion of the ane urysm wassuccessfully image d, th e distal a orta and iliac arteriescould not be imaged with CO2/D SA. In one patient,associated severe aortoilia c occlusive disease was w elldemonst ra ted by the COz/DSA .In eight pat ients, the renal arteries were ima gedbilaterally and wer e free o f significant occlusive dis-ease. A widely patent tran splant renal artery was dem-onstrated in another patient (Fig. 3). Occlusive bi-lateral ma in renal artery disease was dem onst rated inthe remaining three patients (Fig. 4). Findings in-cluded two renal artery occlusions, two high-grade(>90%) s tenoses , and two modera te (>50%) s te-noses. Based on these studies, three patients haveundergone arterial reconstruction, one patient isawaiting renal rcvascularization, and eig ht are beingmanaged nonoperat ively. Arterial reconstructions

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V A SCU LA RSURGERY

Fig. 3. CO2 DS A of renal transplant demonstrates a widelypatent main renal artery (arrow) arising from the externaliliac artery with visualization of segmental and tertiary renalbranches. A proximal external iliac stenosis is als o dem-onstrated.

have included an aortofemoral-unilateral aortorenalbypass, an aortorenal bypass, and an abdom inal aorticaneurysm resection. In all instances operative find-hags cor robora ted those dem onst ra ted by CO 2/DSA .The two patients undergoing renal revascularizationhave been fo l lowed for i and 8 months . Hyper ten-sion and renal f imction have improved in both. Onepatient, at 4 and 8 months af ter surgery, has hadfo l low-up COg/DSA stud ies demonst ra t ing pa tencyof the aortorenal graft an d distal renal ar tery.Common femoral and suprarenal aortic false an-eurysms have be en successfully imaged in two pa-t ients by use o f COg/D SA (Fig . 5 ) . The C O2/ DS Aimages prov ided accurate localization o f the ar ter ialdisease. Bo th ane urysms w ere successfully repaired.

Compl ica t ions o f CO2 / DS A have been l imi ted toa transient deterioration in renal f imction ( increasein serum creatinine >0.5 mg/dl) in three patients inwh om 20 m l o f non ion ic con tras t were necessaryand a nonfatal subendocardial m yocardial infarctionin one patient af ter a popliteal PTA guided byCO2/D SA. One pa t ien t wi th chron ic obstruc t ive pubmon ary disease, develope d tachypnea, tachycardia,and hypertension after the f if teenth CO2 injection.This rapidly resolved. This is the only mo rbidity thatmay be attr ibutable to the use of COg as a contrastagent.

Fig. 4. CO2/DSA aortograrn with occlusion of left renalartery (arrow) and contralateral severe proximal stenosis ofthe right renal artery. The superimposed density overlyingthe aorta represents the superior mesenteric artery. Thispatient underwent a left aortorenal by pas s followed by asubsequent right aortorenal b ypas s. Significant improve-ment in hypertension and re nal fimction has occurred.

D I SCUS S IONThc 33 pa t ien ts who have undergone 40CO2/DSA studies represent only a small fraction of

the 2500 pa t ien ts who have undergone d iagnost icartetiography at our insti tution during the period ofthis study. In this highly selected group, only eightdiagnostic studies and three PTA procedures per-fo rmed wi th CO2/DSA had to be supplan ted wi t2 ,(nonionic) contrast . Inad equate imaging o f collateralpathways and the ar ter ial tree distal to an area ofsevere lower extremity occlusive disease was pred om-inant reason fo r the use of contrast . Nevertheless, thevolume of contrast required to complete a full di-agnostic study was markedly reduced. The benefit ofCO2 in this gro up of patients at high r isk is exem-plified by the thrce patients in wh om even a smallnonionic contrast load induced a transient, biochem -ical deterioration in renal function. Conventionalcontrast ar ter iograms would l ikely have resulted inacute renal failure.

As a gas CO2 has a lower density and layers an-tetiorly with the patient supine. This property a ndthe spatial relationship o f various ar terial segmentsmust be considered in maximizing COg arter ial ira-

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aging. In tortuous or aneurysmal arteries excessivesequestrat ion of CO2 in the non depe nden t segmentsl imited the quali ty of the arterial image in three pa-t ients and prevented effective imaging al together intwo. Altering patient posi t ion to take advantage ofthe bouyanW of CO2 is thus an important elementin CO2 arterial imaging. Elevation of the lower ex-tremities increases flow of CO2 into distal segmentsof the arterial t ree; the prone or decubitus posi t iontakes advantage of the posterior location and pos-terolateral aortic origin of the renal arteries in renalartery imaging. The supine posit ion enhances theima ging o f the visceral arteries.

Although the medical status of pat ients in thisstudy precluded extensive comparison o f C O 2 imageswith standard contrast studies, a few general obser-,~ations concerning the quality and accuracy ofGO2/DSA can be made . First, in those few instanceswhere both contrast and CO2 images were available,arterial architectur e was similar, and althou gh overallvessel enhance men t was greater with nonionic con-trast, this was no t o f practical significance. Th e va-l idi ty of CO2 images when compared to standardcontrast arteriograms was also reported by Hawk insnin his original study. Second , COJDSA findings cor-related very well with the findings at operat ion. Thepatency rate of the arterial reconstructions perform edlends suppo rt to th e accurac y of these images. Finally,the posi tive hemo dyna mic benefi t dem onstrated in 9of 10 patients after PTA attests to the abil i ty ofCO 2/D SA to accu rately mag e critical arterial disease.The use of CO2 to successfully image the PT A ofa critical arterial lesions permits the endovas cular in-tervention when th e risk standard contrast is prohib-itive. It is of interest that the p otential benefits of agaseous contrast agent in translurninal dilation wasfirs t ment ioned by Dot ter and Judldns 12in their clas-sic article on transluminal angioplasty. Other endo-vascular interventions such as ather ectom y may alsobe possible by use of only CO2 as contrast.

Severe bilateral renal artery occlusive disease orunilateral disease in a solitary kidney can be presen tin up to on e third of patients w ith coexist ing hy-pertension and azotem ia? a The identification ofthose patients who could be benefi ted by surgicalcorrect ion has been ham pered by the inaccuracy ofavailable noninvasive screening tests and the neph-rotoxici ty associated with iodinated contrast arterio-grams. We f ound that C O2/D SA facili tated screeningarteriography in this pat ient populat ion and providedsufficient anato mic detail on wh ich revascularization

Fig. 5. Lateral CO2/DSA aortograrn demonstrates a falseaneurysm (arrow) of he juxtarenal aorta. The superior rnes-enteric artery (S) is imaged anterior to th e aorta (14).

could be based. Carbon dioxide/digital subtractionangio graph y was also o f diagnostic value in a singleinvestigation for transplant renal artcW stenosis. Itswide application in this ever enlarging patient pop-ulation deserves fur~&er study.

Complicat ions were rare. The one patient inwhom tachypnea and tachycardia developed mayhave had CO2 pulmonary emboli or hypercarbiacaused by inefficient respiratory excretion of CO2.Silverman e t al. 14 have repo rted the occur rence o ffemoral vein bubbles after the rapid insuffiation ofCO2 during arterial angioscopy in canines. Delete-rious consequences were not observed in these ani-mals. Prev ention of such an occurrence in man canbe accomplished by spacing CO2 injections at least2 minu tes apar t and possibly longer in those patientswith k now n pu lmona ry disease.

This study o f 33 patients with diverse patterns ofarterial disease confirms the safety and clinical use-fulness of CO2/DSA. In patients at risk for contrastrelated complications, patholog ic processes involvingthe abdominal aorta, visceral and renal arteries, andlower extrem ity arterial tree w ere accurately assessedand then correc ted by use of CO z/DSA images as aguide. E ven w hen tortuosi ty or severe occlusive dis-

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e a se p r e c l u d e d e f fe c ti ve C O 2 / D S A i m a g ! n g , a c o m -p l e t e s t u d y w a s p o s s i b le w i t h m i n i m a l n o n i o n i c c o n -t ra s t. F u t u r e r e f i n e m e n t s a n d e x p e r i e n c e w i t h t h i st e c h n i q u e s h o u l d r e s u lt i n w i d e r a n d m o r e v a r i eda p p l i c a t io n s i n t h e a r e a s o f r e n a l t r a n s p l a n t a t io n , e n -d o v a s c u l a r i n t e rv e n t i o n , a n d c o m b i n e d d i a g n o s ti ca n d t h e r a p e u t i c v a s c u l a r p r o c e d u r e s .REFERENCES

1. Schwab SJ, Hlatky MA, Pieper KS, et al. Contrast nephro-toxicity: a randomized controlled trial of a nonionic and anionic radiographic contrast agent. N Engl J Med 1989;320:149-53.2. Parfrey PS, Griffiths SM, Barrett BJ, et al. Contrast materialinduced renal failure in patients with diabetes mellitus, renalinsufficiency, or both. N Engl J M ed 1989;320:143-8.3. Lasse r EC, Berry CC, Talner LB, et al . Pretreatment withcorticosteroids to alleviate reactions to intravenou s contrastmaterial. N Engl J Med 1987;317:845-9.4. Martin-Paradero V , Dixon SM , Baker JD, et al . Risk of renalfailure after major angiography. Arch Surg 1983; 118:1417-20 .5. Burko H, Klatte EC. Renewed interest in gases for contrastroentgenography. AIR 1967;99:645-59.6. Harvard BM , White RR, W alsh II I JF. Experimental studies

in acu te retroperitoneal carbon dioxide insufflation. J U ro.1959;8:481-5.7. Bendib M, Tou mi M, BoudjeUab A. Carboxangiographie etcarboxy angiographie elargie en cardiologie. Ann Radiol1977;20:673-86.8. Meltzer R, Serruys PW, H uge nho ltz PG, Roelandt J. Intra-venous carbon dioxide as an echocardiographic contrastagent. J Clin Ultrasound 1981;9:127-31.9. Turner A, Meyers HI, Jacobson G, Lo W. Carbon dioxidecineangiocardiography in the diagnosis ofpericardial disease.AJR 1966;97:342-9.10. Weaver FA, Pentecost MJ, Yellin AE. Carbon dioxide digitalsubtraction arteriography: a pilot study. A nn V ase Surg1990;4:437-41:11. Hawkins IF. Carbon dioxide digital subtraction arteriogra-phy. AJR 1982;139:19-24.12. Dotte r CT, Judkins MP. Transluminal treatment of arterio-sclerotic obstruction: description o f a new technic and a pre-liminary report o f i ts application. Circulation 1964;30:654-70 .13. Y ing CY, Tifft CP, Ga vras H, Chobanian AV. R enal va~cularization in the azotemic hypertensive patient resistant totherapy. N Engl J Med 1984;311:1070-5.14. Silverman SH, M ladinich DV M, Hawkins IF, Abela GS, See-ger JM. T he use o f carbon dioxide gas to displace flowingblood du ring angioscopy. J VASCSI2RG 1989;10:313 -7.

D I S C U S S I O ND r . E rnes t R ing (S an F ranc i sco , C a l i f . ) . S eve ra l ad -

v a n c e s o v e r t h e p a s t f e w y e a r s h a v e m a d e a r t e r i o g r a p h y asa fe r and m uch be t t e r t o l e r a t ed p rocedure . I n pa r t i cu l a r ,t h e i n t r o d u c t i o n o f l o w o s m o l a r c o n t r a s t m e d i a h a s m a r k -e d l y r e d u c e d t h e s e v e r e p a i n t h a t f o r m e r l y a c c o m p a n i e da r t e r i og raph i c i n j ec t i ons and l ed t o approx im a te ly a s ix fo ldredu c t i on i n t he i nc idence o f m a jo r a l le rg ic r eac t i ons . U n-f o r t u n a te l y , a s w a s p o i n t e d o u t , t h e s e n e w c o n t r a s t a g e n t shave done l i t t l e t o r educe r ena l t ox i c i t y , w h ich i s f a r anda w a y t h e m o s t c o m m o n s e r i o u s c o m p l i c a t i o n o f in t ra a r -t e r ia l con t r a s t adm in i s t r a t i on . T hey_ a l so cos t abo u t $ 1 /m la n d a d d a t le a st $ 1 0 0 t o $ 2 0 0 t o t h e c o s t o f m o s t p r o c e -dures and m i l li ons o f do l l a r s t o t he cos t o f hea lt hca re i nt h e U n i t e d S t at e s.F or s eve ra l yea r s C O 2 has been en thus i a s t i ca l l y advo-c a t e d b y H a w k i n s a s a n i n e x p e n s i v e , n o n t o x i c c o n t r a s ta g e n t f o r a r t e r i o g r a p h y . H o w e v e r , l i k e o t h e r s o m e w h a te c c e n t r i c s o u n d i n g n e w i d e a s , t h i s r e c o m m e n d a t i o n h a sb e e n r a t h e r c o n s i s t e n tl y i g n o r e d b y m o s t o f t h e r e s t o fe s t ab l i shed m ed ic ine , m yse l f i nc luded . F ur the rm o re , s i nceC O 2 c o s t s p r ac t ia l ly n o t h i n g , i t h a s n o c h a m p i o n i n d u s t r yt o f i m d t h e n e c e s s a r y s u p p o r t i n g r e s e a r c h o r t o s u p p l y asa le s fo r ce t ha t w o u ld c r ea t e a m arke t fo r i ts u se .I t i s r ea s su r ing t o f i nd t ha t even w i th t hese k inds o f

obs t ac l e s, a new m e th od t ha t has m er i t w i l l even tua l l y fi ndi ts way into c l inical pract ice .I d o h a v e o n e t e c h n i c al q u e s t i o n f o r D r . W e a v e r . B e i n g

a gas , C O 2 i s com pres s ib l e , an d w he n i n j ec t ed by han dth ro ug h a sy r inge , it r el ea ses i n a f a i rl y unc on t ro l l ed sho r tbu r s t , r a t he r l ike a be lch . H av e yo u l ooke d a t any a l te rna t i vei n j e ct i o n m e t h o d s t h a t m i g h t b e t t e r c o n t r o l t h e f l o w o f the_gas so t ha t i t in j ec ts m ore l ike t he l i qu id agen t s?

D r . W e a v e r . D r . R i n g , c o n c e r n i n g th e c o s t o f C O 2 ,w e a r e s t i l l u s ing t he s am e C O 2 t ank t ha t w e s t a r t ed w i th .I t doe s go a l ong w ay a nd i s t he re fo re ve ry cos t e ff ec ti ve.

F r o m a t e ch n i c a l s t a n d p o i n t , t h e i s su e t h a t y o u b r i n gup i s an im por t a n t one . O ne o f t he i n i t ia l d if fi cu lt ie s w i tht h e s e p r o c e d u r e s w a s o b t a i n i n g a s m o o t h , r a p i d , a n d e v e ni n j e ct i o n o f C O 2 . W e h a v e f o u n d t h a t i f t h e c a t h e t e r i sd e a r e d o f a l l b l o o d b y C O s g a s ju s t b e f o r e t h e i n j e c t io n ,t hen t he C O 2 in j ec t i on w as im proved . B u t i t i s ce r t a in lyn o t a n o p t i m a l s y s te m , a n d p r e s e n t ly H a w k i n s , a t t h e U n i -ve r s i t y o f F lo r ida , i s in t he p roces s o f deve lo p ing an au -tom a ted i n j ec t i on dev i ce fo r C O s m uch l i ke w ha t i s ava i l -ab l e fo r i od ine -con t a in ing co n t r a s t agen t s . I f i n f ac t t ha tcan be deve loped , I t h ink t ha t t he i nd i ca t i ons fo r C O 2c o n t r a s t i n a r t e r i o g r a p h y w i l l b e b r o a d e n e d .D r . J am es S eeg e r (G a inesv i ll e, F l a .) . O ve r t he pas t 8y e a r s a t t h e U n i v e r s i t y o f F l o r id a , a p p r o x i m a t e ly 6 0 0 p a -

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t i e n t s h a v e u n d e r g o n e C O 2 a n g i o g r a p h y u n d e r t h e d i r e c -t i o n o f D r . I r w i n H a w k i n s . T h e f i n d i n g s f r o m t h a t f a ir l yl a r g e n u m b e r o f p a t i e n t s h a v e i n d i c a te d s e v e r al t h i n g s t h a tI th i n k a r e w o r t h e m p h a s i z i n g . I n a d d i t i o n , I h a v e a c o u p l eo f q u e s t io n s f o r t h e a u t h o r s .

W e h a v e f o u n d t h a t f a ir ly g o o d q u a li ty i m a g e s o f t h er e n a l a r t e r i e s , t h e a o r t a , a n d t h e i n f r a i n g u i n a l v e s s e l s d o w nt o t h e l e v e l o f t h e k n e e c a n r o u t i n e l y b e o b t a i n e d b y u s eo f C O 2 a n g i o g r a p h y . T h e a d v a n t a g e s o f t h is t e c h n i q u e a r e( 1 ) i m p r o v e d i m a g i n g o f r u m o r s a n d a r t e r i o v e n o u s f is tu l as ,( 2 ) a b s e n c e o f a l le r g i c c o m p l i c a t i o n s , ( 3 ) e a s e i n d e l i v e r yt h r o u g h v e r y sm a l l c a t h e te r s , w h i c h m a k e s o u t p a t i e n t a n -g i o g r a p h y e a s i e r, ( 4 ) m i n i m a l c o s t , a n d ( 5 ) l a c k o f p a i n i nm o s t p a ti e n t s . I n a d d i t i o n , i n v e r y c o m p l e x d i a g n o s t i c p r o -c e d u r e s , l a r g e v o l u m e s o f g a s c a n b e u s e d f o r m u l t ip l ei n je c t io n s b e c a u s e C O 2 i s r a p i d l y c l e a re d b y t h e l u n g s . M e a -s u r e m e n t o f p H a n d p C O 2 i n p a ti e n ts , e v e n t h o se w i t hp u l m o n a r y d i se a s e , s h o w s m i n i m a l p r o b l e m s . F i n a l ly , p r e -'~ ,m in ar y r e s u lt s f r o m o u r l a b o r a t o r y h a v e s h o w n t h a t C O zm a y b e a g o o d b l o o d d i s p l a c e m e n t a g e n t f o r P T A .

H o w e v e r , t h e r e a r e s o m e p r o b l e m s , a n d I w o n d e r i ft h e a u t h o r s h a v e s e e n a n y o f t h e s e. T o s t a r t w i t h , d e l i v e r yc a n b e d i f f i c u l t , a n d i n s o m e p a t i e n t s i t s e e m s v i r t u a l l yi m p o s s i b l e t o g e t a n a d e q u a t e s t u d y . I w o u l d l i k e t o k n o ww h a t v a r i a b i li t y y o u h a v e s e e n f r o m p a t i e n t t o p a t i e n t i ny o u r a b i l i t y t o g e t a d e q u a t e s t u d i e s u s i n g C O 2 a n g i o g r a -p h y . S e c o n d , w e h a v e s e e n a c o u p le o f p a t i en t s i n w h o mt h e r e w a s a n i n c r e as e i n i s c h e m i a a f t e r C O 2 g a s i n j e c t io n .T h i s a p p e a r e d t o b e a s s o c i a t e d w i t h l e g e l e v a t i o n t o i m -

p r o v e d i s ta l d e l iv e r y o f t h e C O 2 g a s ; w e h a v e n o t s e e n t h isp r o b l e m s i n c e th i s p r a c ti c e w a s d i s c o n t i n u e d . I w o n d e r i ft h is p r o b l e m h a s b e e n s e e n b y t h e a u t h o r s . F i n a ll y , a s y o um e n t i o n e d , t h e r e a r e p r o b l e m s w i t h d e li v e r y , a n d e x p l o s i v ed e l iv e r y c a n o c c u r w i t h h a n d i n j e c ti o n . T h e C O 2 i n j e c to rt h a t D r . H a w k i n s i s d e v e l o p i n g w o r k s s o m e d a y s a n d d o e sn o t w o r k s o m e d a y s . S o a r e l i a b l e d e l i v e r y s y s t e m i s s t i l l al i t t l e b i t away.

D r . W e a v e r . D r . S e e g e r , t h e e x p e r ie n c e a t t h e U n i -v e r s i t y o f F l o r i d a i s o b v i o u s l y f a r g r e a t e r t h a n w h a t w eh a v e h a d t o d a t e .

I n i ti a ll y , w e d i d h a v e a m o d e r a t e a m o u n t o f v a r i a b il it yi n t h e q u a l i t y o f o u r s t u d i e s . I n l a r g e p a r t , t h is w a s d u e t on o t m a x i m i z i n g c h a n g e s i n p a t i e n t p o s i t i o n t o t a k e i n t oa c c o u n t t h e b u o y a n c y o f C O 2 . W i t h g r e a t e r a t t e n t i o n t ot h is t e c h n i c a l p o i n t , t h e q u a l i t y o f o u r s t u d ie s h a s m a r k e d l yi m p r o v e d .

A s f a r a s t h e p r o b l e m w i t h t h e i n j e c ti o n o f C O 2 i sc o n c e r n e d , a s i m e n t i o n e d i n a n s w e r i n g D r . R i n g ' s q u e s -t i o n , w e f i n d t h a t d i s p l a c i n g a l l t h e b l o o d i n t h e c a t h e t e rb y C O 2 b e f o r e i n j e c t i o n m a k e s a b i g d i f f e r e n c e a n d e l i m -i n a t e s t h e e x p l o s i v e e f f e c t y o u d e s c r i b e . T h i s h a s a l s o m a d et h e r e s o l u t io n o f o u r s t u d ie s m u c h b e t t e r.

W i t h r e g a r d t o i n c r e a s e d is c h e m i a : n o , w e h a v e n o th a d t h a t o c c u r . W h a t w e h a v e h a d o c c u r a n d I h a v e n op l a u s i b l e e x p l a n a t i o n f o r i t , i s m a r k e d s y m p t o m a t i c i m -p r o v e m e n t i n l o w e r e x t r e m i t y r e st p a i n o f t w o p a t i e n tsa f t e r t h e C 0 2 a r t e r i o g r a m .