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76 2 Albuterol an d S pa cer -in duc ed A tria l Fibni la t ion (B re ed en , S a fi rs te in )

A lbu tero l and Spacer-inducedA tria l F ib rilla tio n *

Chr is topher C. B reeden , M .D .;t

a nd B en jam in H . Sa firs tein , M .D . , F .G.G.P1

A lbutero l used w ith a spac er dev ice w hich indu ced a tria l

fib rilla tion is desc ribed . Inha led sym pathom im etics h av e

been ex ten sive ly s tud ied fo r the trea tm en t o f a sthm a and

have g en era lly been fou nd to b e sa fe from ca rd iac a rrh y th -

m ias. A rev iew o f the lite ratu re is p re sen ted .

(C h es t 19 90; 98 :762-63)

n asthm atic pa tien t tod ay has m ore therapeu tic op tion s

av aila b le than eve r be fore . V ar iou s oral m edications

are of ten com bined w ith in ha led m edica tions . O fth e inha led

agen ts , a lb u tero l has ga ined grea t accep tance and en joy s a

p rom inen t p osition in the trea tm en t o fasthm a. W e recen tly

trea ted a pa tien t w ho d ev elop ed atria l fib r illa tio n fo llow ing

the use of in ha led a lbu te ro l using a sp acer dev ice, an even t

w e have no t found rep orted in th e lite ra tu re .

C ASE REPORT

A 2 6 -y e ar -o l d m an w ith a fo ur-yea r h is to ry of in term itten t a sthm a

no ted the on set of shor tne ss o f breath on e even in g . H e trea ted

h im selfw ith tw o puffs ofa lbu tero l v ia a m ete red -do se in haler u sing

a spa cer dev ice ( Insp ire ase ). H is cou gh an d dyspn ea im pro ved , b u t

h e no ted the o nset ofpalp ita tio ns w hen he ret ired . U pon aris ing o n

the fo llow ing day; th e p atien t w as n au seated , m ild ly d iapho ret ic ,

a nd st ill h ad p alp ita t ion s.

A n electroca rd iogram tak en in th e em e rgency ro om dem on-

stra te d atria l fib ril la tion . H e w as trea ted w ith a 3 -ad ren erg ic b locker

(Indera l); an d one hour la ter, h is p alp ita t ion s ce ased , a nd a rep eat

e lec troca rd iogram showed a re turn of no rm al s inu s rh ythm . Th e

pa tie n t rep orted s im ilar ep isod es of pa lp i ta tions fo llow ing the u se

o f a lbu tero l w ith th e spac er d ev ice , b u t no t w ith the m ete red -do se

inhaler. The ep iso des had been sho rt-l ived and had not re qu ired

em e rgency ro om visits .

F o llow ing th e use of alb u te ro l w ith th e spa cer (Insp irea se) , the

p atien t deve lop ed p alp ita tion s, a nd an electroca rd iogram (F ig 1 )

ta ken 3 0 m inu tes af ter inh alat ion dem on stra ted a tria l fib rilla tio n ,

w hich sub seq uen tly reverted to n orm al sin us rhy thm w ith out

th erapy . T he fin d in gs from m edic al ev alu atio n , inc lud ing thyro id

profi les, H olter c ard iac m on ito r ing , e cho ca rd io graph y , an d a c ard iac

stress s tud y , w ere norm a l. Pu lm ona ry fu nc tion stu d ie s dem onstra ted

m ild v aria b le airflow obstruc tio n . N o oth er oral o r in haled m edica-

tion s w ere u sed , an d th e p atien t h ad n o sig n if ican t c ard iac h is to ry .

He disco n tin ued us ing th e spacer dev ice h u t con tinued th erap y

*F rom the D epartm en t o f Pu lm ona ry M ed icine, Sain t M ichae l’s

M edical C ente r, N ew a rk , N J .

tP u lm on ary F ellow .

tD irec to r o f P ulm on ary M ed icine and A ssociate P rofe sso r o f M ed -

ic in e, N ew Jersey C olle ge o f M ed ic in e a nd D en tis tr y.

w ith a lhu tero l v ia a m eter ed -dose inha le r w ithou t a re tu rn of

pa lp i ta tions or ar rhy thm ias . A n exe rcise s tud y w ith card ia c m on i-

to rin g fa iled to docum en t any isch em ic change s o r ar rhy thm ia s,

e i the r w ith o r v t’ itho u t in ha led a lbu tero l.

D ISCUSSION

A tria l fib r illa tio n is an u nstab le ca rd ia c arrh y thm ia w hich

fo rtuna te ly has no t been rep orted to occur w ith the use of

inh aled b ronchod ila to rs . S ince L and e t a l in 19 67 s ugg ested

the ex is ten ce of a spec ific 3 2 -adrenerg ic recep to r caus in g

pred om inan tly b ronchod ila tion , m any agen ts have em erged

and prov ided therapeu tic alte rna tives fo r b roncho spas tic

d iso rde rs. A lb u te ro l , a syn the tic ca techo lam ine , has been

w ide ly used since its in troduc tion in 1 96 8 . I t d em o ns tr at ed

a pro long ed dura tio n o faction and m ore bronch ia l sp ec ific ity

w hen com pared to its fo reru nners , iso pro te rna l, isoe tha rine ,

and ep inephrine . M any stud ies su bstan tia ted these c la im s ,

and none found any serious card iac stim ula tio n .

Saf ir ste in e t a l,2 in a stud y of 1 5 ste ro id -d ep enden t

as thm atic su b jec ts , fou nd no a lte ra tio n in pu lse , b lood

pressure , o r rhy thm fo llow ing sing le o ra l doses o f 4 -m g and

6 -mg a lb u te ro l tab le ts . T a ttersfie ld an d M cN icho l, in a

do ub le -b lind tr ia l, found no increase in heart ra te w ith

in haled a lbu tero l un les s th e sub ject w a s g iven five tim es th e

recomm ended do se . Sh im et a l’ foun d no increase in

a rrh y thm ias us in g inha led iso pro te reno l excep t fo r o ne

pa tien t w ho deve loped a tria l fib r illa tio n wh ile rece iv ing

concurren t in tra ven ous am in ophylline . M onteneg ro et al

fo und a h igher, a lthough no t s ta tistica lly sign ifican t, m ci-

dence o f a tria l p rem atu re beats durin g pu lm onary fun ction

te stin g us ing inh aled isop ro te ren o l, com pared to isoethar ine .

R esp ira to ry m an euvers are k nown to alter ca rd iac rhy thm,

slow ing AV condu ctio n and sino atr ia l ac tiv ity . Th ese e ffe cts

are m ed ia ted by vag al afferen ts in the v isce ra l p leu ra

st im u lated a t to ta l lung capac ity an d vaga l ef fe ren ts inn er -

va tin g th e hea rt. L am b et alb d em ons tra ted the se ef fec ts and

had one case ofAV d isso cia tio n w ith n od al tach ycard ia w hich

had rap id spon taneous reso lu tion .

It is im pro bab le tha t a trial fib rillation occurred as a resu lt

of the prop ellan t. F reo n and o ther f lu o rocarbon s are kn ow n

to depress m yocard ia l con trac tility , a lte r co nduc tion , an d

l owe r the th resho ld of m yo cy tes to the arrhy thm ogen ic

ef fec ts o f sym path om im e tic am ines ; it is es tim ated tha t in

v ivo , th is w ou ld tak e 1 2 to 24 con secu tive b reaths to see

su ch an e ffec t.

The w id esp read diffic u lt ies w ith th e pa tie n t’s com plianc e

in u sin g m etered -do se inh ale rs h av e led to th e use o f

in halatio n aid s c alled spac ers . S pac er d ev ices ac t a s either

ho ld ing cham be rs fo r the ae roso l spray o r as dev ic es w hich

ac t to p ro long th e a ero so l tim e w ith in th e spa cer so as to

red uce o rop ha ryn gea l depos itio n .

F icu iu : 1 . E lec troc ard iog ram taken 30 m in ute s a fte r

using alb u te ro l w ith reserv o ir- typ e sp ac er d ev ice .

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CHEST I 98 I 3 I SEPTEMBER , 1990 76 3

Tube spa cers are sim ple d ev ices w hich red uce the am ount

of m ed ica tion depo sited a t th e oropharyn x from 80 percen t

to 40 percen t. Spacers w ith h o ld ing cham bers su ch as the

on e used by our pat ien t va ry in c apa city f rom 140 m l to 6 00

m l. B ecause th ese spacers a llow m ore tim e fo r evapo ra tion

of th e prope llan t, pa rtic le size b ecom es sm alle r, and thus

mo re ae roso l is dep osi ted on the sm alle r a irw ays.9 It is o ur

co nten tio n th at alb u te ro l trig ge red atria l fib rilla tio n in o ur

o therw ise h ealthy y oung a sthm a tic su b je ct, p rin cip ally

th roug h the increased d ose ava ilab le by u sing the spacer

dev ice . T hese ep isod es o f palp ita tio ns ce ased w hen th e

m etered -do se inh ale r w a s u sed w ith ou t th e spac er d ev ic e ,

ye t the pa tien t w as still ab le to o b tain sym ptom atic re lie f

C ard iac ad renerg ic recep to rs a re p redom inan tly -recep-

to rs , b u t up to 20 p ercen t h ave b een repo rted to be -

recep to rs. “ ‘ Th is m ay accoun t fo r the w ide v ar iab ility in

card iac stim ula tio n . W ith the inc reasing use o fsp acer dev ices

and w ith im proved m eans of de live ring 1)ronchod ila to rs to

the en dobro nch ia l system , c loser ob serva tion of ca rd iac

a rrh y thm ias sho u ld be u ndertaken .

CONCLUS ION

A hea lth y 2 6-year-o ld m an w ith as thm a d eve lo ped re -

p ea ted ep iso des of a tria l fib r illa tio ns us in g a lbu te ro l v ia a

m ete red -do se inha le r w ith a spacer dev ice . No s uc h ep is od es

o ccu rred w hen the dev ice w a s d isco n tinued . W e po stu late

tha t such arrhy thm ias m ay resu lt from increased depo sitio n

of the sym pathom im etic d rug , albu te ro l, w hen u sed w ith a

spacer d ev ice .

REFERENCES

1 Land AM , A rno ld A , M cA uliff JP D iffe ren tia tion of recep to r

sy stem s activ ate d by sym path etic am ine s. N atu re 19 67 ; 214 :597 -

98

2 Sa firs te in BH , F ortu na to FD , G elb B . Com parison of sa lbu tam ol

combinat ion w ith theo phyllm ne in s tero id dependent as thm atics.

JM ed S oc N J 1980; 7 7 :275 -77

3 T atters fie ld AE , M cN icho l MN . S alb u tam o l and isopro te ren o l:

a do uble-b lin d tria l to com pa re bro nch od ila to rs and card io vas -

cu lar ac tiv i ty . N E ngI J M ed 1969; 28 1:132 3-2 6

4 Sh im C S , Scher SM , W ill iam s M H Jr. E ffec t o f bro nchod ila to r

ag en ts o n arrhy thm ia. NY S tate J M ed 1976; (N ov ):1 973 -7 6

5 M onteneg ro H D , C hes ter EH , H on es PK . C ard ia c ar rhy thm ia

d urin g ro u tin e tests of pu lm onary fun ctio n in pa tie n ts w ith

ch ro n ic obs tru ctio n o f airw ay s. C h est 1 978 ; 73 :13 3-39

6 L am b LE , D erm ks ian C , Sarnoff CA . S ign if ic an t ca rd ia c

a rrh ythm ia s indu ced by common resp ira to ry m aneuvers. Am J

Ca rd io l 195 8; (N ov) :56 3-7 1

7 D rug Th er Bu ll 19 76 ; 14 :21-22

8 N ewm an SP , P av is D , G a rlan d N . E ffe cts of var iou s inh ala tio n

m odes on the depos itio n o f rad ioac tiv e p ressurized ae roso ls . E ur

J R espir D is 198 2; 63 :(su ppl 1 19) :57

9 Ahm ad D . E ffe cts of aeroso l p rop ella n ts in airw ay fu nc tion . In :

E ps tein B , ed . M etered d ose in ha lors : an in te rna tio nal w ork-

shop . M iss issaug a, O ntario : A stra P harm aceu tica ls, Inc . 1 984 :2 2-

6

10 P rod uct in fo rm atio n : P roven ta l. K en ilw orth , N J: S he ring C orp .

1987

A sp ira tion Pneum on ia due to

D iffu se C e rv ica l H ype ros tos is *

C lay W arn ick , M .D .; t M icha el S. Sherm an, M .D . , FC .C .P ;t a nd

Ra ymon d W L esser, M .D 4

D iffuse id iop ath ic ske leta l h ype rostos is p rev ious ly has been

reported to cause a num ber o f ex tra sp in a l m an ife sta tions

in clu d ing d ysp hag ia , re sp ira to ry d istre ss , d ysp hon ia and

ce rv ical m y elo pa thy . W e rep ort a case o f ce rv ica l D ISH so

ex ten sive as to in te rfe re w ith the sw allow in g m echan ism

and lead to asp ira tion . P a tien ts w ith D ISH who have

m ech an ica l com press ion of th e p oste r io r pha ry nx m ay be

a t h ig h risk fo r a sp iratio n . (Ches t 1 99 O 9 8: 76 3-6 4)

L DISH = d iffuse id io pa th ic sk ele ta l hy peros to sis

S en ile anky los ing hyp erostos is o f th e sp ine w as first

desc ribed in 1 950 by Fores tie r and Rotes-Q uero l’ w ho

repor ted a se ries o f n ine p a tien ts w ith b ony ou tg row ths

a rising f rom th e an te rio r asp ect of th e ve rteb ral b od ies and

ex tend ing upw ard over the d isc spaces . S ince ex trasp ina l

m an ifesta tions a re comm on, and a t tim es ex tens ive , R esn ick

e t al2 appropria tely renam ed th e cond ition d iffuse id io pa th ic

sk ele ta l hy pe ros tosis (D ISH ) in 19 78 an d fu rthe r c lar ifie d

th e criteria for d iag no sis. A t th at tim e , he de fined the

necessary rad io log ic c rite ria fo r d iagn osis : (a ) flow ing ca lc i-

fica tion and oss ification alon g the an te ro la te ra l aspec t o f a t

le ast fo ur con tigu ous ver teb ral bod ies , (b ) rela tive preser-

va tion of in te rverteb ra l d isc he ig h t in the invo lved area

w ith ou t the presence of degenera tive d isc d isease , an d (c )

the absence of ap ophy sea l jo in t bony anky los is, sac ro iliac

jo in t e rosion or in traa rticu la r osseou s fu sion .

T h e pa thog en esis o f th is cond ition is no t known. T he

pha ryn gea l m asses form ed can b e q u ite ex ten sive and m ayoccasional ly b e v isua lized or p a lp ated a t the tim e of the

phy sic al ex am ina tion . P rev io us ly repo rte d com plications of

D ISH hav e inc lud ed dy sph ag ia, ex tra sp ina l m an ife sta -

tion s,7 and occas iona lly resp ira to ry d is tress , d ysp hon ia and

cerv ica l ‘ Th is is the f irs t reported case of a

pa tien t w ith asp ira tion pneum onia secondary to D ISH .

CASE REPORT

A 75-year-o ld w hite w om an w as trans ferred to o ur h osp ita l fo r

th e eva lua tio n o f asp ira tio n p neum onia . T he p atie n t had p rev iou sly

com pla ined of c erv ical st iffn ess w hich b egan fiv e y ears prio r to

adm issio n . Tw o years p rio r to adm issio n , she b egan to have d iff icu l ty

sw allow ing liqu ids and so lids. Th is pro gre ssed to th e poin t w heresh e b egan to ch ok e on he r fo od and then w as adm itte d to a loca l

ho sp i ta l fo r fev er an d cough . S he w as fo und to h ave an a sp ira t ion

pn eum on ia and trea ted w ith h ig h-d ose pen ic illin . Sh e w as th en

transfe rred fo r a su rg ica l p ro ced ure .

*F rom the tP u lm onary D iv is ion , D epartm en t o f M edic ine , an d th e

jD epartm en t o fO to la ryn go logy , H ahnem ann U niv ers ity llosp ita l,

Ph i ladelph ia .

Rep rin t reques ts: D r She rm an , H a hn em an7 l U n iver sity H ospita l,

MaiLs top 107, P hilad elph ia 19102-1192

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