Abstract
Objective: To assess the effectiveness of magnesium sulphate in
the prophylaxis of postoperative atrial fibrillation in patients undergoing elective
coronary aortic bypass grafting or valvular heart surgery in terms of reducing
its incidence and decreasing the length of hospital stay.
Methods:
This study which was conducted
at Queen Alia Heart Institute from June 2009 to June 2010 on 308 patients who
underwent elective coronary artery bypass grafting or valvular heart surgery. Patients
were divided into two equal groups, the magnesium-treated and control groups
(154 each). Then each group was subdivided into patients who underwent coronary
artery bypass grafting alone (n = 102), and patients underwent valvular surgery
with or without coronary artery bypass grafting (n = 52). In the treatment group, patients were given
3.0gm of magnesium sulphate intra-operatively, and later on for the first 4
consequent post operative days.
Results:
About 8.4% developed atrial
fibrillation in the treatment group in contrast 23.3% in the control group (P
< 0.001).
In
the subdivided groups, those patients who underwent only coronary artery bypass
grafting, 7.8% and 23.5% developed atrial fibrillation in the treatment and
control group respectively. In the group of patients who underwent valvular
heart surgery with or without CABG, 5 patients (9.6%) developed atrial
fibrillation in the treatment group compared to 15 patients (28.8%) in the
control group.
Atrial fibrillation developed after 34 ± 10.52 hours
in the treatment group in comparison to 38 ± 11.23 hours which is statistically
non-significant. The length of hospital stay was 6.01 ± 2.15 days in the treatment
group while it was 5.95 ± 1.85 days in the control group which was also found
to be statistically non-significant.
Conclusion: Use of magnesium sulphate, both intraoperativley and postoperatively
proved to be safe and effective in reducing the incidence of post operative
atrial fibrillation in patients undergoing elective coronary artery bypass
grafting or valvular heart surgery, but with no obvious significant effect on
hospital stay.
Key
words: Magnesium sulphate,
Post operative atrial fibrillation, Prophylaxis.
JRMS
December 2011; 18(4): 10-15
Introduction
Atrial Fibrillation (AF) is a relatively common postoperative
arrhythmia seen early after cardiac surgery with a frequency ranging between (6-40%).(1-3)
It commonly occurs between 0-4 days,(4,5)
with peak incidence on the second to third postoperative day.(2,3,5) Its onset may
be associated with hemodynamic instability, increased risk of thromboembolism
or stroke, prolonged hospitalization and significant increase of hospital morbidity.(6,7) The aim of this study was to assess
the effectiveness of magnesium sulphate in the prophylaxis of AF in patients
undergoing elective CABG
or valvular heart surgery in terms of reducing its incidence and decreasing the
length of hospital stay.
Methods
This was a prospective, randomized, controlled trial
of intravenous magnesium sulphate (MgSO4) vs. intravenous saline in
patients undergoing elective cardiac surgery for the first time at Queen Alia
heart institute conducted over one year between June 2009 and June 2010. The
study was approved by the local ethical committee of Jordanian Royal Medical
Services.
The study primary endpoint was the occurrence of an
episode of AF lasting ≥ 30 minutes or hemodynamic instability due to AF
regardless of episode duration. Secondary endpoint was the length of hospital
stay.
The age, history of hypertension or diabetes mellitus,
total pump and aortic cross clamp time, time onset of AF and hospital stay
duration were recorded.
Exclusion criteria included: Emergency surgery (within
12 hrs), previous history of AF or other arrhythmias, permanent pacemaker,
renal failure, intolerance to β- blockers, respiratory airway disease requiring
regular β-adrenergic agonists such as salbutamol.
All patients were randomized into either the study or
control group, had normal sinus rhythm prior to surgery.
Patients were divided into two major equal groups,
each consisted of 154 patients i.e. the magnesium (study group) and saline one (control
group). Then each group was subdivided into patients undergoing isolated CABG
(n=102), and patients undergoing valve surgery with or without CABG (n = 52).
Patients in the study group received 3 gm of MgSO4
while the control group received a 100 cc of 0.9% intravenous saline intra-operatively
by the anaesthesiologist after removal of the cross clamp; then the same dose
for the next 4 postoperative days. Patients stopped receiving either choice if
AF occurred. Regarding general anaesthesia, surgical techniques and patient
monitoring were standardized for all patients. All patients
were monitored with continuous
ECG monitoring (telemetry) for the first 2 days post operatively either in ICU1
or step down ICU2.
Values are presented as means ± standard deviation and
percentages. Chi-square was used to analyze the results, differences were
considered to be statistically significant when P value < 0.05, in addition
to that, the test was used for comparison of patients in terms of duration of
hospitalizations.
Results
The demographic data did not differ significantly
between the two groups. The mean age of the treatment and control groups was
comparable 60.1 vs. 60.5 years respectively as well as the gender, 74.6% vs.
75.3% being males. Hypertension was found in 63.6% (98 patients) of the
magnesium group and in 62.3% (96 patients) of the control group. DM was found
in 33.7% and 33.1% of the magnesium and control group respectively.
Regarding mean aortic cross clamp time in the
magnesium group was 55.7+14.2 minutes (Range 38 – 106 min) vs. 56.2+13.5
minutes (Range 40-104) in the control group whereas the average total pump time
was 103+23 minutes (Range 56-156) vs. 103.4 minutes (Range 56-157). Both
parameters were found to be statistically non-significant (P > 0.05) (See Table
I & II).
The incidence of postoperative AF was 8.4% in the
magnesium treated group (N=13) while it was 25.3% in the control group (N=39),
which is statistically significant (P < 0.001 -See Table II).
When dividing the patients into those who underwent
CABG only and those who underwent valve surgery with or without CABG, the
incidence of AF was 7.8% vs. 23.5% (P value < 0.01) in the magnesium and control
groups respectively. On the other hand, the incidence of AF in the CABG plus
valve group was 9.6% vs. 28.8% (P < 0.05) in both the magnesium and control
groups respectively. It was seen that the incidence of AF is more in the valve
patients than the CABG group with or without MgSO4 treated, which is
due partly to the effect of valve pathology.
Concerning the timing of onset of AF and hospital
stay, the onset of AF in the magnesium treated group occurred in 78% of
patients on the second day, 15% on the first day, with mere 7% in the third
day, in contrast to the control group with 75% on the second day, 10% on the
first day, 15% on the third day.
The results of our study are summarized in
the below scheme:
The onset of AF was 34.6±10.5 hrs in the treatment
group while it was 38±11.2 hrs in the control group which found to be
statistically non-significant. The length of hospital stay was 6.0 ± 2.2 days
in the treated group while it was 5.6 ± 1.9 days in the magnesium group, when comparing it with patientswho developed
AF, it was found to be statistically non-significant, so AF did not have an
impact on the length of hospital stay (Table III).
Discussion
Despite the significant advances in the peri-operative
management of postoperative AF, its incidence has not decreased during the last
decade with consequent morbidities and increased risk of heart failure, renal
failure and strokes.
The mechanism behind the occurrence of post operative
AF has not been clearly identified, but the most likely cause is
multi-factorial in origin which might include
advanced age,(4,5,8,9) preoperative withdrawal of β-blockers,(5,7,8)
impaired cardiac function,(5,8) myocardial ischemia and
reperfusion,(5,8) chronic obstructive lung disease,(5,8)
excessive catecholamines(5,8,9) and electrolyte imbalances
particularly hypomagnesaemia which has been considered as an independent
predictor of postoperative AF.
Almost 80% of patients undergoing cardiac surgery have
reduced both ionized and total serum magnesium levels postoperatively,(5,8)
which might be attributed to several causes, mainly hemodilution related to cardiopulmonary bypass,(5,9)elevated catecholamine
levels, which may be caused by abrupt withdrawal of β-blockers,(9)
advanced age in addition to increased urinary magnesium loss due to diuretic
use.(5)
Changes in magnesium concentration have significant
effects on cellular metabolism and structure, as well as stabilizing the
cellular transmembrane potential of myocardial cells, suppressing excessive
cellular calcium influx, and reducing the severity of reperfusion injuries,(5,9,10)
this can be done by inhibiting L and T type calcium channels, which will reduce
sinus firing and increase AV (atrioventricular) node refractoriness.(3,8,11,12)
For these reasons, magnesium has been suggested to be
effective in the prophylaxis of AF after cardiac surgery; however a lot of
debates on its use and benefits are present, with more necessity to identify
the proper dose and timing of magnesium administration.
Table I. Demographic and clinical characteristics
|
Variable
|
All Surgeries
|
CABG (n =
102)
|
Valve ± CABG
|
P value
|
|
MgSO4
n = 154
|
Control
n = 154
|
MgSO4
n = 102
|
Control
n = 102
|
n = 52
MgSO4
n = 52
|
Control
n = 52
|
|
Male
|
74.6%
|
75.3%
|
77.3%
|
74.2%
|
74.2%
|
72.5%
|
NS*
|
|
Female
|
25.4%
|
24.7%
|
26.7%
|
25.8%
|
25.8%
|
27.5%
|
NS
|
|
Age
(median)
|
60.1 years
|
60.5 years
|
60.9%
|
60.5%
|
61.2%
|
61.5%
|
NS
|
|
HT
|
63.6%
|
62.3%
|
62.1%
|
63.1%
|
62.4%
|
62.5%
|
NS
|
|
DM
|
33.7%
|
33.1%
|
33.5%
|
33.6%
|
33.8%
|
32.9%
|
NS
|
Table II. Intraoperative and postoperative characteristics of
patients
|
Variable
|
All Surgeries
|
CABG (n =
102)
|
Valve ± CABG
|
P value
|
|
MgSO4
n = 154
|
Control
n = 154
|
MgSO4
n = 102
|
Control
n = 102
|
n = 52
MgSO4
n = 52
|
Control
n = 52
|
|
TPT*
|
103.4
± 22.66
|
102.9 ± 21.95
|
105 ± 19.52
|
104 ± 21.62
|
106 ± 22.52
|
104 ± 42
|
NS**
|
|
TPT in patients with AF
|
104.5 ± 21.56
|
104.8 ± 21.92
|
106 ± 21.42
|
105 ± 22.52
|
106 ± 21.52
|
103 ± 52
|
NS
|
|
ACX^
|
55.65
± 14.25
|
56.32 ± 13.92
|
57.42 ± 12.92
|
55.95 ± 13.52
|
57.82 ± 12.42
|
56.92 ± 12.12
|
NS
|
|
ACX in patients with AF
|
57.42 ± 13.45
|
56.56 ± 12.82
|
56.52 ± 13.10
|
54.95 ± 12.52
|
56 ± 11.92
|
54.82 ± 12.60
|
NS
|
|
Patients with AF
|
13
|
39
|
8
|
24
|
5
|
15
|
P<0.05
significant
|
* Total Pump Time
** Non-significant ^
Aortic Cross Clamp
Table III. Timing of Atrial fibrillation and length of hospital
stay
|
Variable
|
Mg S04
(n = 154)
|
Control
(n = 154)
|
P value
|
|
Onset
of AF (hr)
|
34.65 ± 10.52
|
38 ± 11.25
|
NS
|
|
Length of hospital stay (days)
|
6.01 ± 2.15
|
5.95 ± 1.85
|
NS
|
Although the prophylactic use of MgSO4 has not
yet verified been of the conflicting evidences,(5,6)
Still it is considered to be attractive tool because
of its low cost, safe when administered slowly, moreover the decline in serum Mg
with cardiopulmonary bypass which does not recover until the third day
coinciding with the period during which AF develops.
In our study, we had an incidence of about 23% AF in
the control group, in contrast to just 8% in the treated one P < 0.001,
which means dramatic and significant decrease in the incidence of AF upon the
administration of MgSO4.
It is undoubtly evident that the incidence of AF is
within the range reported in the literature (16-40%).(1-3) Fevzi
toraman and his colleagues(9) conducted comparative study on
200 patients which showed dramatic decrease in the incidence of post cardiac
surgery AF from 24% to mere 2%.
Moreover, another study conducted by Hiroki Kohno and
his colleagues(5) on 200 patients illustrated significant
decrease in the incidence of post operative AF from 32% to 16%.
Furthermore, a study by Naito Y and his colleagues(13)
showed obvious decline in the incidence of postoperative AF from 43.8% to 10%,
in addition to the Muhammad Bakhsh study(3) had significant
response to MgSO4 administration in that postoperative AF decreased
from 23% to just 9%, at the same time, the meta analysis conducted by Miller et
al(1) concluded that prophylactic MgSO4
is effective for the prevention of AF after CABG with decrease in its incidence
from 28% to 18%. The same findings were supported by another meat analysis of Henyan.(14)
However, a study conducted by Mehmet Kaplan and his colleagues(4)
found no significant difference in the incidence of AF upon the infusion of MgSO4,
that is to say MgSO4 infusion alone is not sufficient for the
prophylaxis of AF.
Another study by Richard C,(6) found
also no difference in the incidence of AF after infusion of MgSO4
between patients who received IV MgSO4 or placebo (26.4% versus 24.3
respectively).
The different results seen from the above mentioned
articles might be attributed to the dosage of MgSO4 given, in
most clinical trials that have shown effective prophylaxis, the amount of
magnesium per day given no greater that 15 mmol with reported mean serum levels
after each dose were within the normal physiological range,(5)
in contrast to high magnesium
dose >50mmol which
had the least effect, hence we use low dose magnesium in our study with less
demand or need for serum levels determination.
Since AF usually develops between first post operative
days to the fourth one, with associated hypomagnesemia during that, we intended
to give MgSO4 during this period which proved to have
significant role in the prevention of this arrhythmia.(4,5)
Concerning the risk analysis of post operative AF, we
found that age, gander, hypertension, diabetes, total pump time, aortic cross
clamp were not significant factors in the development of AF, which is also
found in a study conducted by Richard C. cook and his colleagues.(6)
We found the same effects of MgSO4 infusion on patients
undergoing valve surgery with or without CABG, in comparison to those with CABG
only, as in the case of valve with or
without CABG, there was 66.6% decrease in the incidence of AF upon administration
of magnesium, while there was 66.8% decline in the incidence of AF in patients
with CABG only, which is almost the same effect, however the incidence of AF is
more in valve patients(15) as seen in our study 28.8% whereas
it is 23.5% in the CABG group, on the other hand, meta analysis by S Miller and
his colleagues(1) showed that MgSO4 was
more effective in trials with CABG surgery alone than that when CABG was
combined with valve surgery.
Regarding the length of hospital stay, no
statistically significant difference was found between the treatment and
control group, which is also seen in other studies;(1,9) in
contrast to the study by Kaplan that found significant change in the length of
hospital stay with Mg SO4 in fusion.
Furthermore, the timing of onset of AF was found to be
insignificant when comparing both groups, meanwhile the majority of patients
developed AF on the second day, then the first day which indicated that MgSO4
infusion has no effect on the timing of onset of AF.
Limitations
of the Study
First limitation is the absence of continuous ECG
monitoring, except for the first and second day for both the treated and
control group, after that the arrhythmia was usually detected either by early
morning routine ECG or symptomatic patients with clinical signs or even asymptomatic accidental findings.
Because this limitation was the same in each group, it is unlikely that this
affected the results of our study.
The second limitation of our study was the definition
of significant AF, as several definitions exist according to the duration of
AF; therefore we attempted to select relatively long duration (> 30 minutes)
because it is likely that the longer the AF duration, the more prominent the
benefits of the magnesium treatment will be.
Conclusion
Use of magnesium sulphate, both intra-operatively and
postoperatively proved to be safe and effective in reducing the incidence of
post operative AF in patients undergoing elective CABG or valvular heart
surgery, with no obvious significant effect on hospital stay.
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