Vi amin C in p e en ion o a ial ib illa ion a e co ona y a e y bypass g a : double blind
andomized clinical ial [in Fa si]
Sa zaeem M and Shayan N
Teh an Uni e si y Medical Jou nal 2014;71(12):787–793
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This ial was included in a me a-analysis on i amin C and a ial ib illa ion by Ha i Hemilä:
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288748708_Vi amin_C_in_p e en ion_o _a ial_ ib illa ion_a e _co ona y_a e y_bypass_g a _
Double_blind_ andomized_clinical_ ial
1
Vi amin C in p e en ion o a ial ib illa ion a e co ona y a e y bypass g a :
double blind andomized clinical ial [in Fa si]
Mahmood eza Sa zaeem1, Nasim Shayan2*
Teh an Uni e si y Medical Jou nal 2014;71(12):787–793.
Abs ac
Backg ound and Objec i e: A ial ib illa ion is he mos common a hy hmia a e ca diac
su ge y. As an an ioxidan , i amin C has a c ucial ole in educing he incidence o pos -ope a i e
a ial ib illa ion. The p esen s udy was ca ied ou o e alua e he impac o i amin C
adminis a ion in educing he incidence o pos -CABG a ial ib illa ion.
Me hodology: In his double-blind pa allel clinical ial, 170 pa ien s wi h co ona y a e y disease
who unde wen CABG we e di ided in o wo g oups o in e en ion and con ol acco ding o he
able o andom numbe s and ecei ed i amin C and placebo, espec i ely. The g oups had no
s a is ically signi ican di e ence in e ms o demog aphic and clinical cha ac e is ics. The
in e en ion g oup ecei ed 2 g in a enous i amin C he nigh be o e su ge y. The medica ion was
con inued o 5 days as 500 mg wice a day. A e su ge y, he g oups we e e alua ed and compa ed
in e ms o impo an ou comes o he s udy, pa icula ly he occu ence o a hy hmia, leng h o
s ay in ICU, and leng h o s ay in hospi al.
Findings: A o al o 118 men and 52 women wi h a mean age o 59.1±9.8 yea s we e en olled in
he s udy in he wo g oups o i amin C and placebo (each wi h 85 pa ien s). The incidence o
pos ope a i e a ial ib illa ion was 12.9% and 29.4% in he i amin C and con ol g oups,
espec i ely (p=0.009). The leng h o ICU s ay was 2.5±1.4 days in he i amin C g oup and
3.0±1.6 days in con ols (p=0.035), and he leng h o hospi al s ay was 6.6±1.5 days in he i amin
C g oup and 8.2±2.3 days in con ols (p<0.001).
Conclusion: Vi amin C is a ela i ely sa e, cheap, and well- ole a ed ea men wi h low
complica ion. Since he incidence o pos -CABG a ial ib illa ion was educed by 44% in he
i amin C g oup, he d ug can be p esc ibed as a p ophylaxis o p e en ion o pos -CABG a ial
ib illa ion.
Keywo ds: a ial ib illa ion, co ona y a e y bypass, i amin C
2
In oduc ion
A ial ib illa ion (AF) is he mos common a hy hmia ollowing ca diac su ge y. I is a
po en ial ac o o p olonged ime o hospi aliza ion and occu ence o neu ological and
enal complica ions. The incidence o pos ope a i e AF a ies om 30% and 40% o
co ona y bypass and al e su ge y alone, espec i ely, o 50% o simul aneous co ona y
bypass and al e su ge y [1]. The incidence o AF has been epo ed o ange be ween 12
o 74% in pa ien s unde going non-ca diac su ge y [2]. The ime o occu ence o AF is
be ween he second and he ou h day ollowing su ge y, wi h he highes incidence on
he second day a e su ge y. Among pa ien s who de elop pos -ope a i e AF, i
con inues un il he ou h day in 90% o pa ien s and un il he end o he six h day in 94%
o hem [3]. Pos ope a i e AF is conside ed an independen ac o o mo ali y [4].
Gi en he a o emen ioned easons, inding a me hod o p e en ing his complica ion
migh be e ec i e in educing he du a ion o hospi aliza ion and he occu ence o o he
complica ions as well as educing cos s. Se e al ac o s a ec he incidence o
pos ope a i e AF, in lamma o y and oxida i e ac o s being he mos impo an [5].
Oxida i e damage has been shown in he hea issue o pa ien s wi h AF by some s udies
[6], while o he s udies ha e shown he ele a ion o se um le els o myoca dial oxida ion
ma ke s in pos ope a i e AF such as ni i e pe oxide and supe oxide [7]. An ioxidan s
including i amin C, N-ace ylcys eine, and s a ins can dec ease he se um le els o
oxidan s [8, 9]. Since acco ding o s udies conduc ed in o he coun ies, an ioxidan s
we e shown o play an impo an ole in educ ion o he incidence o pos ope a i e AF,
and gi en he limi a ions o he p e ious s udies, i seemed necessa y o ca y ou his
s udy.
3
Me hodology
In his pa allel double-blind clinical ial, he e ec o i amin C on he incidence
o AF and he leng h o s ay a ICU and in he hospi al a e co ona y bypass su ge y
was e alua ed in wo g oups o in e en ion and con ol in Sha ia i Hospi al in Teh an
du ing Augus 2012-Janua y 2013.
Pa ien s wi h co ona y a e y disease (in angiog aphy) who we e candida e o
co ona y a e y bypass we e included in he s udy. The exclusion c i e ia we e; 1- age
o e 80 yea s; 2-pa ien s wi h AF be o e su ge y; 3- pa ien s wi h al ula hea disease,
a hy hmia, o ca diac conduc ion block o any deg ee; 4- pa ien s using a pacemake ,
5- pa ien s wi h ch onic lung, li e , o kidney disease; 6- pa ien s wi h o he hea
su ge ies along wi h co ona y bypass g a ; 7- his o y o an ia hy hmic d ug
consump ion; 8- sick sinus synd ome; 9- pa ien s wi h symp oms o his o y o u ina y
calculi; and 10- his o y o i amin C consump ion du ing he las h ee mon hs.
Vi amin C is a well-known an ioxida i e medicine in he medical li e a u e and
can be pu chased o e he coun e (OTC) and has no signi ican oxici y in he dose
p esc ibed in his s udy; howe e , a comple e desc ip ion was p o ided o he subjec s
and an in o med consen was ob ained om hem. The s udy was app o ed by he e hics
commi ee o he Resea ch Depu y o Teh an Uni e si y o Medical Sciences. The
equi ed da a we e collec ed by a nu sing mas e du ing a pe iod o six mon hs, h ough
a ending he bedside o pa ien s who unde wen co ona y bypass su ge y, and using an
in o ma ion o m de eloped o his pu pose. The esea ch me hod was he same o all
pa icipan s, so ha bo h he in e en ion and con ol g oups we e ope a ed by he same
su gical eam and ecei ed a simila p e- and pos ope a i e ICU ca e.
The esea ch ool was a da a collec ion o m wi h all he equi ed speci ica ions
including he speci ic code o he pa ien s (assigned o each pa ien acco ding o he
egis a ion o m), he ile numbe , he p ocedu e ype (o pump/on pump), leng h o
s ay a he ICU and in he hospi al, incidence o AF, o he complica ions, and he ime
o discha ge.
All ele an in o ma ion was collec ed om he admi ed pa ien eco ds (his o y,
su gical p ocedu e, and ICU pa ien s’ shee s). The s a is ical popula ion consis ed o
pa ien s wi h co ona y a e y disease (in angiog aphy) who we e candida es o
co ona y bypass su ge y a he ca diology wa d o Sha ia i Hospi al. Using he sample
size o mula, 170 pa ien s we e examined in his s udy. The sample size in his s udy
was de e mined acco ding o a simila s udy (Ca nes). In he a o emen ioned s udy
4
pe o med on 86 pa ien s, he incidence o pos ope a i e AF in he con ol g oup was
34.9% which dec eased o 16.3% a e consump ion o i amin C; he e o e, o ge a
simila esul wi h a con idence le el o 95% and an accu acy o 100%, and assuming a
di e ence o a leas 20% in he in e en ion and con ol g oups, 116 pa ien s we e
equi ed. Howe e , by aking he isk o loss, unce ain y, insu icien in o ma ion, and
po en ial p oblems a he ICU, 170 pa ien s we e s udied. They we e di ided andomly
in o wo g oups o in e en ion and con ol, each including 85 pa ien s, and we e
andomly assigned o ecei e placebo o i amin C. Pa en e al o m o i amin C
(asco bic acid) was used, and each ampoule con ained 500 mg i amin C pe 5 mL
which was in used in a enously (in 100 mL o no mal saline). Since pa ien s we e old
in he in o med consen ha hey we e o ecei e ei he i amin C o placebo (no mal
saline), hey we e unawa e o hei ea men g oup.
The p esen s udy was a double-blind pa allel g oup clinical ial, because nei he
he pa ien s no he heal h ca e wo ke s we e awa e o he medica ions in he in usions
( i amin C o no mal saline), excep he esea che who was awa e acco ding o he
code labeled on se um. The in e en ion g oup ecei ed a o al o 7 g in a enous
i amin C as 2 g ( ou ampoules) 12 hou s be o e he p ocedu e and 500 mg (one
ampoule) wice a day o i e days a e he p ocedu e.
The pa ien s in he con ol g oup ecei ed placebo (in a enous no mal saline).
The equency and du a ion o adminis a ion o he placebo in he con ols g oup was
comple ely he same as he in usion o i amin C in he in e en ion g oup. Depending
on su geon’s disc e ion, he pa ien s we e ope a ed in acco dance wi h he s anda d
me hod o co ona y bypass along wi h myoca dial pe usion p o ec ion by ca dioplegia
o he o -pump me hod. The pa ien s we e ea ed a he ICU a e su ge y and
con inuously moni o ed wi h ECG unde cons an su eillance o ained nu ses. In case
o any a hy hmia, ECG was e alua ed by he esea che s. ECG was pe o med on a
daily basis a e ans e ing he pa ien s o he wa d.
The p ima y objec i e o his s udy was o e alua e he incidence o AF las ing a
leas 10 minu es o equi ing immedia e he apeu ic in e en ion due o symp oma ici y
o hemodynamic ins abili y. A hy hmias we e con olled wi h amioda one and all
p esc ip ions we e eco ded. Da a we e analyzed wi h s uden ’s - es and χ2 using
SPSS-17, while p<0.05 was conside ed signi ican .
5
Resul s
A o al o 170 pa ien s, including 118 men (69.4%) and 52 women
(30.6%) we e examined in his s udy. The age ange was be ween 38 o 78 yea s
wi h a mean o 59.1±9.8 yea s. The s udy g oups we e ma ched in e ms o
demog aphic and clinical cha ac e is ics, and compa isons showed no signi ican
di e ence be ween he in e en ion and con ol g oups in his ega d. The e o e,
hese a iables we e simila ly dis ibu ed among he wo g oups (Table 1).
The leng h o s ay a he ICU had a signi ican di e ence (0.49 days)
be ween he in e en ion and con ol g oups (p=0.035), i.e. pa ien s in he
in e en ion g oup who ecei ed i amin C s ayed o a sho e du a ion a he
ICU compa ed o he con ols. The di e ence was 1.53 days o he du a ion o
hospi aliza ion (p<0.001). The e o e pa ien s in he in e en ion g oup we e
hospi alized one and a hal day less han he placebo g oup (Table 2).
The ela ionship be ween any a hy hmia (VT, PVC, AF) and i amin C
consump ion was de e mined, and a signi ican ela ionship was obse ed
acco ding o χ2 s a is ics (p=0.009). The incidence o AF in i amin C g oup was
12.9%, which was signi ican ly lowe han in he con ol g oup (29.4%). In
addi ion, i amin C consump ion educed he incidence o PVC (12.9% in he
in e en ion g oup e sus 28.2% in he con ol g oup) (p=0.014); howe e , no
signi ican ela ionship was obse ed be ween he dec eased incidence o VT
and consump ion o i amin C (p=0.99) (Table 3).
6
Table1: Compa ison o demog aphic and clinical cha ac e is ics o he in e en ion
and con ol g oups
Va iable
In e en ion
g oup
(n=85)
Con ol
g oup
(n=85)
p
Age (yea s)*59.1±10.4 59.1±9.1 0.981*
Gende (male)** 57 (67.1%) 61 (71.8%) 0.506**
Heigh *165.6±9.6 165.6±9.1 0.974*
Weigh *72.5±12.2 73.1±13.9 0.779*
Smoking** 21 (24.7%) 29 (34.1%) 0.178**
His o y o diabe es** 35 (41.2%) 29 (34.1%) 0.342**
Blood c ea inine le el*1.09±0.35 1.07±0.20 0.688*
His o y o hype ension** 47 (55.3%) 44 (51.8%) 0.645**
His o y o CVS** 2 (2.4%) 2 (2.4%) 1.000**
His o y o ch onic lung disease** 2 (2.4%) 1 (1.2%) 1.000**
Le en icula ejec ion
ac ion*45.3±7.4 46.9±7.1 0.155*
On-pump su ge y** 58 (68.2%) 65 (76.5%) 0.230**
* Values a e exp essed as mean±SD and S uden ’s - es
** Values a e exp essed as numbe (pe cen ) and χ2;
p<0.05 was conside ed signi ican
Table 2: Compa ison o he mean leng h o s ay in ICU and hospi al in he in e en ion and con ol
g oups
Va iable
In e en ion
g oup
(n=85)
Con ol
g oup
(n=85)
p
Leng h o s ay in ICU (day) 2.5±1.4 3.0±1.6 0.035*
Leng h o s ay in hospi al (day) 6.6±1.5 8.2±2.3 <0.001*
* S uden ’s - es , alues a e exp essed as mean±SD;
p<0.05 was conside ed signi ican
Table 3: Compa ison o he equency o a hy hmia in hea bea in he in e en ion and con ol
g oups
Va iable
In e en ion
g oup
(n=85)
Con ol
g oup
(n=85)
p
A ial ib illa ion (AF) 11 (12.9%) 25 (29.4%) 0.009*
P ema u e en icula con ac ion
(PVC) 11 (12.9%) 24 (28.2%) 0.014**
Ven icula achyca dia (VT) 1 (1.2%) 2 (2.4%) 0.99*
* χ2 s a is ical es ; alues a e exp essed as numbe (pe cen )
Discussion
7
The esul s ob ained om his s udy demons a ed he signi ican impac o i amin C in
educing he incidence o AF ollowing co ona y bypass su ge y. Few s udies ha e been ca ied ou
in his ega d; howe e ou esul s a e consis en wi h hose ob ained by p e ious s udies [9-11].
In a s udy by Ca nes on 11 dogs wi h pacemake -induced elec ical econs uc ion, apid a ial
pacing was shown o lead o inc eased pe oxyni i e, which pe se is associa ed wi h AF in humans.
In addi ion, a ial asco ba e le el dec eased ollowing apid a ial pacing. As an an ioxidan ,
asco ba e is capable o p e en ing he e ec s o oxida i e s ess p oduced om high ac i i y o
a ium ( h ough pacing o inc eased sympa he ic one, and ca diac su ge y-induced
ischemia/ epe usion inju y). Mo eo e , he e ec i e e ac o y pe iod (ERP) was educed 24 o 48
hou s a e pacing. They also di ided 86 pa ien s who unde wen CABG and had sinus hy hm
be o e su ge y in o wo g oups o in e en ion and con ol. The in e en ion g oup ecei ed 2 g
i amin C in a single-dose 12 hou s be o e CABG and hen 500 mg wice a day o i e days. The
incidence a e o pos -CABG AF was 16.3% and 34.9% in he in e en ion and con ol g oups,
espec i ely [9]. Ko an zopoulos in es iga ed he e ec o o al i amin C on he incidence o AF in
44 pa ien s who de eloped con inuous AF ollowing elec ical ca dio e sion. Pa ien s who ecei ed
an ioxidan agen s, excep o s a ins, we e excluded. The du a ion o con inuous AF was measu ed
wi h ECG. The pa ien s we e di ided in o wo g oups o con ol and i amin C (each wi h 22
pa ien s). The second g oup ecei ed 2 g i amin C in a single-dose 12 hou s be o e coo dina ed
elec ic shock ollowed by 500 mg i amin C wice a day o se en days. WBC, CRP, and
ib inogen we e e alua ed a he i s , hi d, and se en h days a e ea men . Vi amin C was ound
o be e ec i e in educing he ecu ence o AF. One week a e elec ical ca dio e sion, he
p e alence o AF was 4.5% and 36.3% in he in e en ion and con ol g oups, espec i ely
(p=0.024%). Compa ed wi h baseline, consecu i e measu emen s o in lamma o y indices did no
change conside ably in he con ol g oup, while hey dec eased signi ican ly in he in e en ion
g oup [10]. In a ecen s udy on he e ec o i amin C in educing he incidence o AF a e on-
pump myoca dial ascula su ge y, Papoulidis di ided he pa ien s in o wo g oups o con ol and
i amin C supplemen a ion (each consis ing o 85 pa ien s). The incidence o pos ope a i e AF was
44.7% and 61.2% in he in e en ion and con ol g oups, espec i ely (p=0.041%) [11].
Acco ding o he indings o his s udy, adminis a ion o asco bic acid be o e and a e
bypass su ge y is help ul in educing he incidence o AF and dec eases he leng h o s ay a he
ICU and in he hospi al. These esul s emphasize he impo ance o i amin C adminis a ion du ing
CABG su ge y. Asco bic acid is a sa e, cheap, and well- ole a ed ea men wi h a low a e o
complica ions. The e o e, in e en ional p og ams and p o ocols o adminis a ing asco bic acid
be o e and a e CABG can help p e en ing AF a e co ona y bypass su ge y.
8
Acknowledgemen
We gi e ou g a i ude o he espec ul nu ses and all indi iduals who helped us conduc and
comple e he s udy. This a icle is he esul o a esea ch p ojec en i led “E alua ion o he impac
o i amin C in educing he incidence o a ial ib illa ion a e co ona y a e y su ge y in D
Sha ia i hospi al”, which was app o ed in he Teh an Uni e si y o Medical Sciences in 2011 wi h
unde code 90-03-94-15572 and was ca ied ou wi h he suppo o Teh an Uni e si y o Medical
Sciences.
Re e ences
1. Echahidi N, Piba o P, O'Ha a G, Ma hieu P. Mechanisms, p e en ion, and ea men o a ial ib illa ion a e
ca diac su ge y. J Am Coll Ca diol 2008;51(8):793-801.
2. Vapo ciyan AA, Co ea AM, Rice DC, Ro h JA, Smy he WR, Swishe SG, e al. Risk ac o s associa ed wi h
a ial ib illa ion a e nonca diac ho acic su ge y: analysis o 2588 pa ien s. J Tho ac Ca dio asc Su g
2004;127(3):779-86.
3. A anki SF, Shaw DP, Adams DH, Rizzo RJ, Coupe GS, Vande Vlie M, e al. P edic o s o a ial ib illa ion
a e co ona y a e y su ge y. Cu en ends and impac on hospi al esou ces. Ci cula ion 1996;94(3):390-7.
4. El-Chami MF, Kilgo P, Thou ani V, La ou OM, Delu gio DB, Guy on RA, e al. New-onse a ial ib illa ion
p edic s long e m mo ali y a e co ona y a e y bypass g a . J Am Coll Ca diol 2010;55(13):1370-6.
5. Takenaka K, Ogawa E, Wada H, Hi a a T. Sys emic in lamma o y esponse synd ome and su gical s ess in
ho acic su ge y. J C i Ca e 2006;21(1):48-53; discussion 53-5.
6. Bian K, Dou sou MF, Mu ad F. Vascula sys em: ole o ni ic oxide in ca dio ascula diseases. J Clin
Hype ens (G eenwich) 2008;10(4):304-10.
7. Ramlawi B, O u H, Mieno S, Boodhwani M, Sodha NR, Clemen s RT, e al. Oxida i e s ess and a ial
ib illa ion a e ca diac su ge y: a case-con ol s udy. Ann Tho ac Su g 2007;84(4):1166-72; discussion 1172-3.
8. Liu T, Li G, Ko an zopoulos P, Goude enos JA. S a ins and p e en ion o a ial ib illa ion in pa ien s wi h
hea ailu e. In J Ca diol 2009;135(3):e83-4.
9. Ca nes CA, Chung MK, Nakayama T, Nakayama H, Baliga RS, Piao S, e al. Asco ba e a enua es a ial
pacing-induced pe oxyni i e o ma ion and elec ical emodeling and dec eases he incidence o pos ope a i e
a ial ib illa ion. Ci c Res 2001;89(6):E32-8.
10. Ko an zopoulos P, Kole is TM, Koun ou is E, Dimi oula V, Ka anikis P, Pappa E, e al. O al i amin C
adminis a ion educes ea ly ecu ence a es a e elec ical ca dio e sion o pe sis en a ial ib illa ion and
a enua es associa ed in lamma ion. In J Ca diol 2005;102(2):321-6.
11. Papoulidis P, Ananiadoua O, Chal a zoulisa E, Ampa zidoub F, Kou sogiannidis C, Ka aiskosa T, e al. The
ole o asco bic acid in he p e en ion o a ial ib illa ion a e elec i e on-pump myoca dial e ascula iza ion
su ge y: a single-cen e expe ience: a pilo s udy. In e ac Ca dio asc Tho ac Su g 2011;12(2):121-4.
9
