Albuterol and Spacer-induced Atrial Fibrillation.pdf
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7/28/2019 Albuterol and Spacer-induced Atrial Fibrillation.pdf http://slidepdf.com/reader/full/albuterol-and-spacer-induced-atrial-fibrillationpdf 1/2 76 2 Albuterol an d S pa cer-in duc ed A trial Fibnilation (B re ed en , S a fi rs te in ) Albuterol and Spacer-induced Atrial Fibrillation* Christopher C. Breeden, M .D .;t and Benjamin H. Safirstein, M.D. , F.G.G.P1 Albuterol used with a spacer device which induced atrial fibrillation is described. Inhaled sympathomimetics have been exten sively studied for the treatment of asthma and have generally been found to be safe from cardiac arrhyth- mias. A review of the literature is presented. (Chest 1990; 98:762-63) n asthmatic patient today has more therapeutic options available than ever before. Various oral medications are often combined with inhaled medications. Ofthe inhaled agents, albuterol has gained great acceptance and enjoys a prominent position in the treatment ofasthma. We recently treated a patient who developed atrial fibrillation following the use of inhaled albuterol using a spacer device, an event we have not found reported in the literature. CASE REPORT A 26-year-old man with a four-year history of intermittent asthma noted the onset of shortness of breath one evening. He treated himselfwith two puffs ofalbuterol via a metered-dose inhaler using a spacer device (Inspirease). His cough and dyspnea improved, but he noted the onset ofpalpitations when he retired. Upon arising on the following day; the patient was nauseated, mildly diaphoretic, and still had palpitations. An electrocardiogram taken in the emergency room demon- strated atrial fibrillation. He was treated with a 3-adrenergic blocker ( Inderal); and one hour later, his palpitations ceased, and a repeat electrocardiogram showed a return of normal sinus rhythm . Th e patient reported similar episodes of palpitations following the use of albuterol with the spacer device, but not with the metered-dose inhaler. The episodes had been short-lived and had not required emergency room visits. Following the use of albuterol with the spacer (Inspirease), the patient developed palpitations, and an electrocardiogram (Fig 1) taken 30 minutes after inhalation demonstrated atrial fibrillation, which subsequently reverted to normal sinus rhythm without therapy. The findings from medical evaluation, including thyroid profiles, Holter cardiac monitoring, echocardiography, and a cardiac stress study, were normal. Pulmonary function studies demonstrated mild variable airflow obstruction. No other oral or inhaled medica- tions were used, and the patient had no significant cardiac history. He discontinued using the spacer device hut continued therapy *From the Departm ent of Pulmonary Medicine, Saint Michael’s Medical Center, Newark, NJ. tPulmonary Fellow. tDirector of Pulmonary Medicine and Associate Professor of Med- icine, New Jersey College of Medicine a nd D en tis tr y. with alhuterol via a metered-dose inhaler without a return of palpitations or arrhythmias. An exercise study with cardiac moni- toring failed to document any ischemic changes or arrhythmias, either with or vt’ithout inhaled albuterol. DISCUSSION Atrial fibrillation is an unstable cardiac arrhythmia which fortunately has not been reported to occur with the use of inhaled bronchodilators. Since Land et al in 1 9 67 s ugg ested the existence of a specific 32-adrenergic receptor causing predominantly bronchodilation, many agents have emerged and provided therapeutic alternatives for bronchospastic disorders. Albuterol, a synthetic catecholamine, has been widely used since its introduction in 1968. It d em o ns tr at ed a prolonged duration ofaction and more bronchial specificity when compared to its forerunners, isoproternal, isoetharine, and epinephrine. Many studies substantiated these claims, and none found any serious cardiac stimulation. Safirstein et al,2 in a study of 15 steroid-dependent asthmatic subjects, found no alteration in pulse, blood pressure, or rhythm following single oral doses of 4-mg and 6-mg albuterol tablets. Tattersfield and McNichol, in a double-blind trial, found no increase in heart rate with inhaled albuterol unless the subject was given five times th e recommended dose. Shim et al’ found no increase in arrhythmias using inhaled isoproterenol except for one patient who developed atrial fibrillation while receiving concurrent intravenous aminophylline. Montenegro et al found a higher, although not statistically significant, mci- dence of atrial premature beats during pulmonary function testing using inhaled isoproterenol, compared to isoetharine. Respiratory maneuvers are known to alter cardiac rhythm, slowing AV conduction and sinoatrial activity. These effects are mediated by vagal afferents in the visceral pleura stimulated at total lung capacity and vagal efferents inner- vating the heart. Lamb et alb demonstrated these effects and had one case ofAV dissociation with nodal tachycardia which had rapid spontaneous resolution. It is improbable that atrial fibrillation occurred as a result of the propellant. Freon and other fluorocarbons are known to depress myocardial contractility, alter conduction, and lower the threshold of myocytes to the arrhythmogenic effects of sympathomimetic amines; it is estimated that in vivo, this would take 12 to 24 consecutive breaths to see such an effect. The widespread difficulties with the patient’s compliance in using metered-dose inhalers have led to the use of inhalation aids called spacers. Spacer devices act as either holding chambers for the aerosol spray or as devices which act to prolong the aerosol time within the spacer so as to reduce oropharyngeal deposition. Ficuiu: 1 . Electrocardiogram taken 30 minutes after using albuterol with reservoir-type spacer device. wnloaded From: http://journal.publications.chestnet.org/ on 05/24/2013
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Transcript of Albuterol and Spacer-induced Atrial Fibrillation.pdf
7/28/2019 Albuterol and Spacer-induced Atrial Fibrillation.pdf
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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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