Research Article

SALBUTAMOL NEBULISATION: IS
IT A PREDISPOSING FACTOR FOR
IJCRR
Section: Healthcare POSTOPERATIVE ATRIAL FIBRILLATION
IN CORONARY ARTERY BYPASS GRAFTING
Sci. Journal
Impact Factor
4.016

PATIENTS?

Megha Shah1, Hetal D. Shah2

1
Assistant Professor, Dept of Pharmacology; B.J.Medical College, Ahmedabad, Gujarat, India; 2Sr. Consultant & Clinical Lead Cardiac Anaes-
thesia and Intensive Care. Narayana Multispeciality Hospitals, Ahmedabad, Gujarat, India.

ABSTRACT
Background: Atrial fibrillation (AF) is one of the known complications of cardiac surgery and represents a major cause of
morbidity. However, improvements in surgical and anaesthesia technique and controlling various predisposing factors have not
helped to curb the incidence. Therefore, search is going on for various modalities to decrease the incidence.
Aim: This retrospective study was conducted to evaluate the risk of AF with nebulised ß2 agonists in postoperative cardiac
bypass surgery patients.
Methods: In this observational study, data of 100 eligible patients operated for coronary artery bypass grafting (CABG) was col-
lected. Patients were divided in two groups:
Group A: Patients who had received postoperative nebulised salbutamol
Group B: Patients who had not received postoperative nebulised salbutamol
The data was analyzed for onset, duration, severity, treatment, outcome of post operative AF (POAF) and also regarding dose,
duration of salbutamol.
Results: POAF occurred frequently in patients who had received nebulised salbutamol (p<0.05). ICU and hospital stay was also
prolonged in Group A. However, none of the patients had fatal postoperative complication.
Conclusion: Salbutamol nebulisation in post CABG patients could be an additional risk factor for POAF.
Key Words: Atrial fibrillation, ß2 agonists, Post cardiac surgery patients, Salbutamol nebulisation

INTRODUCTION of surgery, intraoperative arrhythmia may increase risk of AF

Atrial fibrillation (AF) is most common type of arrhythmia
in post cardiac surgery patients; more common with valvu-
lar surgeries. It may cause hemodynamic disturbances and
so increase in ICU stay and thus treatment cost. It can also
increase stroke and other thromboembolic complications.(1)
Post operative atrial fibrillation (POAF) has been associated
with higher risk of postoperative congestive heart failure
(CHF) and renal insufficiency. (2)
Various preoperative factors like past history of AF, concom-
itant valvular disease and intraoperative factors like duration
post surgery.(3,4) Increased catecholamine and ionic imbal-
ance during the postoperative period may be associated with
AF.(5) Other factors like pericardial inflammation, hypoka-
lemia, systemic arterial hypertension could also increase
risk.(6) However, the exact cause for AF post cardiac surgery
is not well established. Hence, the search is on to find out
other predisposing factors and preventing measures.
A study (7) published in American journal of respiratory criti-
cal care medicine has showed an association between major
cardiovascular events and ß2 agonists in asthma and chronic
obstructive pulmonary disease (COPD) patients. They ob-

Corresponding Author:
Megha Shah, Assistant Professor, Department of Pharmacology; B.J.Medical College, Ahmedabad, Gujarat, India; E mail:mkshah_80@yahoo.
com.
Received: 16.07.2015 Revised: 20.08.2015 Accepted: 17.09.2015

Int J Cur Res Rev | Vol 7 • Issue 19 • October 2015 16

 Shah et. al.: Salbutamol nebulisation: is it a predisposing factor for postoperative atrial fibrillation in coronary artery bypass grafting patients?
served modest increase in risk of myocardial infarction (MI)
in those taking ß2 agonists (OR=1.67). (7) Over many years,
various cardiovascular adverse events, including MI, heart
failure, ventricular ectopy, AF and sudden cardiac death re-
sulting from ß2 agonists use in patients with COPD have
accumulated.(8,9,10)
However, the risk of AF with ß2 agonist is not confirmed in
post coronary artery bypass grafting (CABG) patients. As
ß2 agonists are used for excess respiratory secretions after
cardiac bypass surgery, our study aimed to examine the risk
of AF with nebulised ß2 agonists in post cardiac surgery pa-
tients.
MATERIALS AND METHODS
This observational, retrospective study was conducted at a
tertiary cardiac care hospital, Gujarat. The study was in ac-
cordance with the Helsinki Declaration. Information about
patients operated for CABG was obtained from case records
and also verified with computer records during one year pe-
riod. A well-designed case record form was used to collect
the data of the recruited patients.
Patients with risk for AF like concomitant valvular surgery,
left main coronary artery disease , age>70 yrs, preoperative/
intraoperative arrhythmias (including AF) and hypo or hy-
perkalemia, COPD, Asthma, poor left ventricle (LV) func-
tion, recent MI, renal impairment, CHF, hypothyroidism,
patients requiring IABP and longer duration of CPB(> 120
mins ) and aortic-cross clamp time were excluded . Also,
patients on ß blockers and drugs with arrhythmogenic poten-
tial, diuretics, angiotensin converting enzyme (ACE) inhibi-
tors or corticosteroids were excluded.
Data of eligible patients were collected. Patients did receive
their routine medications till the day prior to surgery except
anticoagulants which were stopped three days prior as per
institute protocol. All other variables like myocardial protec-
tion, closure of pericardium, elective maintenance of potas-
sium and analgesia remained same in both the groups.
The patients were given salbutamol or normal saline nebu-
lisation therapy for lung recruitment, to remove excess res-
piratory secretions every 8 hrly for three days after surgery
as per hospital protocol. Based on post CABG nebulisation
exposure, data of total 100 patients was collected (equal
number of patients taken in both groups):
Group A: Patients had received nebulised salbutamol post
CABG (n= 50)
Group B: Patients had received saline nebulisation post
CABG (n= 50) phase. No difference in incidence was reported between on
17
Information about baseline characteristics of patients,
CABG (on pump or of pump), occurrence of POAF and use
of nebulisation in post-operative period was obtained from
case record forms. In POAF patients details regarding onset,
duration, treatment, outcome and other complications were
also analysed.
Statistics
Data analysis was performed using chi square test and stu-
dent’s t test (Sigma stat 3.5software, trial version).The p
<0.05 was considered to be statistically significant.
RESULTS
The demographic characteristics of patients are presented
in Table-1. All participants were between the 30-70 years.
Majority of them were between 50-60 years of age. No dif-
ference in gender regarding development of AF was noted.
Majority of patients underwent off pump CABG.
As shown in table-2, 18 patients in group A while 6 in group
B had POAF. AF was common on 2nd and 3rd post opera-
tive day. We did not observe any POAF case after discharge
from ICU. Average duration for conversion of AF into sinus
rhythm was 1 to 1.5 hrs after onset of first episode. Table-3
depicts the incidence of POAF between on pump and off
pump CABG cases . Mean length of ICU stay was 5 days in
group A while 3 days for group B(5 ± 1.9 vs. 3± 1.3 days; p
= 0.163, C.I.-1.080 to 5.080).Hospital stay is also prolonged
in group A than group B(10 ± 6.1 vs. 7 ± 3.5 days; p = 0.262
, C.I.-2.481 to 8.481). All POAF patients were treated with
inj. amiodarone 5mg/kg i.v. bolus followed by 1 gm/day as
i.v. infusion. Oral amiodarone was started to overlap the in-
fusion. Patients were given beta blockers too in postopera-
tive period. The choice was made by cardiologist.
Potassium correction was done to maintain range of 4-4.5
mmol/L. However, none of the patients had developed fatal
or non fatal complication either due to AF or due to omis-
sion of salbutamol. There was no incidence of acute renal
failure (ARF), cardiovascular stroke or embolization in any
patients.
DISCUSSION
Incidence of POAF varies from 25 - 40 % for cardiac surgery
and 50-60% after valvular surgery. (11) The present study re-
vealed that salbutamol nebulisation could be a risk factor for
AF in post CABG patients (p<0.02). It usually occurs within
3 days postoperatively but can occur at any point in recovery
pump and off pump cases (1), which is in accordance with
our study. Use of antiarrythmic drugs, ICU and hospital stay
Int J Cur Res Rev | Vol 7 • Issue 19 • October 2015
 Shah et. al.: Salbutamol nebulisation: is it a predisposing factor for postoperative atrial fibrillation in coronary artery bypass grafting patients?
were also increased in salbutamol group as compared to
group-B.
The competing risks and benefits of ß2 agonist use has been a
topic of much discussion. A meta-analysis of 33 randomized
placebo-controlled trials of patients with obstructive lung
disease revealed that a single dose of ß agonist increased
heart rate by 9 beat/min and reduced potassium concentration
by 0.4 mmol/L compared with placebo. ß2 agonist treatment
for 3 days to 1 year has increased the risk of cardiovascular
events more than twofold compared with placebo in trials. (10)
Though exact aetiology is not known, multiple factors can
predispose to POAF. Hypoxia due to airflow obstruction or
due to drug, may precipitate POAF.(12, 13) A study found that
despite treatment with ß agonists, airflow obstruction caused
hypoxemia and precipitated MI.(7)
Observations from various studies evaluating risk
of AF proposed various theories.
Breeden and colleagues (14) observed risk of arrhythmias with
not only systemically administered but also with inhaled se-
lective ß agonists. Myocardial contraction mediated by ß2
receptors present in heart, could be a reason for association
of ß2 agonists with tachycardia, an abnormal ECG and atrial
fibrillation. (15)
A meta-analysis of 3,840 patients undergoing heart sur-
gery found 14% reduction in incidence of POAF between
the control group (placebo) and ß receptor blocker group
(P<0.00001). (15) Increased plasma levels of ß2 agonists also
reported though given by inhalation with low systemic ab-
sorption. (16)
There are several possible explanations for our finding of
risk of POAF in CABG patients. A study by Au DH and
colleagues suggested increased rate and force of contrac-
tion, decreased peripheral vascular resistance with increased
pulse pressure and changes in serum potassium and mag-
nesium levels with ß2 agonists, which may affect conduc-
tion pathways in the heart. (7) Stimulation of ß2 receptors can
cause intracellular shifts of potassium into skeletal muscle
and lead to hypokalemia. Hypokalemia is associated with in-
creased risk of AF, more in pts with COPD or taking diuret-
ics or corticosteroids. (6) Other probable causes include inter
individual susceptibility and physical alterations of cardiac
structure from incisions on atria.
Amiodarone, beta blockers, calcium channel blockers and
others like procainamide, methylprednisolone and magne-
sium have been used for prevention of POAF. Atrial pacing
has also gained popularity as non pharmacological preven-
tive measure for POAF. As most of the anti arrhythmic drugs
used for prevention have their own side effects, substitution
of inhaled salbutamol in high risk CABG patients could be
Int J Cur Res Rev | Vol 7 • Issue 19 • October 2015
beneficial with other measures.
Our study also has certain limitations. The results of study
cannot apply to all ß2 agonists as salbutamol was the only
ß2 agonist studied based on hospital protocol. Being a retro-
spective study with small sample size, there are chances of
bias due to unrecognized confounding factors. Further rand-
omized controlled trials are required to clarify association of
ß2 agonist in POAF. Nevertheless, according to our literature
search, this is first type of study evaluating risk of AF with ß2
agonists in post CABG patients.
Despite these limitations, we believe that this study should
heighten concern over use of salbutamol in patients undergo-
ing cardiac surgery. To help clarify the issue, our study could
serve as a landmark for future clinical trials to find out risk
of POAF with ß2 agonists.
CONCLUSION
The current study revealed that when other predisposing fac-
tors are taken care of, elective omission of salbutamol nebu-
lisation may decrease AF and associated morbidity in post
CABG patients. Until proved, the available evidence needs
to be examined closely in an attempt to assess whether ß2-
agonists should be administered to post cardiac surgery pa-
tients.
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Table 1: Demographic data

Demographic characteristics Number of patients
Group A (n=50) Group B(n=50)
(1) Age (years)
30-40 04 (8%) 06 (12%)
40-50 12 (24%) 09 (18%)
50-60 18 (36%) 21 (42%)
60-70 16 (32%) 14 (28%)
(2) Sex
Male 36 (72%) 35 (70%)
Female 14 (28%) 15 (30%)
(3) LV function

Good 26(52%) 28(56%)

Moderate 24(48%) 22(44%)
(4) Type of CABG
On pump 04(8%) 05(10%)
Off pump 46(92%) 45(90%)

Table 2: POAF in both the groups

POAF p value
Exposure Yes No
Group A (salbutamol ) 18 32 p = 0.010*

Group B (saline) 06 44

Chi-square test was used for statistical analysis. *p <0.05 was considered to be statistically significant.

Table 3: POAF in on pump and off pump CABG cases

POAF Group A Group B Total
On pump 2 2 4
CABG (n=9)
Off pump 16 4 20
CABG (n=91)

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