CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 7, August 2013
AFRICA
263
in the postoperative period in patients with valve diseases.
1,2
Individually or combined, the presence of these risk factors may
make the weaning from CPB difficult and may cause severe left
and right ventricular failure after the CPB procedure.
Treatment methods for patients who cannot be weaned from
CPB or develop low cardiac output after CPB include use of
inotropic agents, vasodilators, intra-aortic balloon pump, insertion
of a balloon pump into the pulmonary artery, implementation of
right ventricular assist devices and extracorporeal membrane
oxygenisation. A newly developed agent, levosimendan, is now
available. It exhibits positive inotropic activity by increasing the
ionised calcium sensitivity of cardiac troponin C and facilitating
calcium binding to the myofilaments. Additionally, it exhibits
vasodilator effects on the decrease in intracellular calcium level
by allowing the ATP-sensitive potassium channels to be opened.
3
Levosimendan differs from other positive inotropic drugs with
features such as increasing contractility without increasing
myocardial oxygen consumption, improving coronary perfusion
with its vasodilator activity, reducing preload and afterload by
vasodilatation in the pulmonary, renal, splanchnic, cerebral and
systemic arteries as well as in the saphenous, portal and systemic
veins.
8,9
There are many reported studies of levosimendan being used
in cardiac surgery. In many of these studies, levosimendan was
started after cardiac surgery or during CPB weaning.
6
In only a
few studies, levosimendan was started before CPB.
Tritapepe
et al
. reported that a short infusion of levosimendan
before coronary artery bypass grafting (CABG) protected
the myocardium and improved postoperative haemodynamics.
Levosimendan-treated patients had lower postoperative troponin
I concentrations and a higher cardiac index, suggestive of a
preconditioning effect.
10
Leppikangas
et al
. administered levosimendan to patients who
underwent combined aortic valve and coronary bypass surgery
for 24 hours before surgery. They found that both CI and stroke
volume were higher in the levosimendan group and concluded
that in patients undergoing risky cardiac surgery, levosimendan
improved haemodynamics compared with placebo.
11
Brezina
et al
. showed that levosimendan infusion after the
induction of general anaesthesia in high-risk cardiac surgery
patients resulted in better outcomes for the length of hospital
stay and 30-day mortality rate, compared with patients receiving
dobutamine and milrinone.
12
In another study by Tritapepe
et
al
., intravenous bolus administration of levosimendan over a
10-minute period before initiation of bypass resulted in less
myocardial injury, a reduction in tracheal intubation time,
less requirement for inotropic support and a shorter length of
intensive care unit stay, compared with placebo.
13
In our work, a dose titration study showed that even at a
minimal dosage of levosimendan, an increase of approximately
12 ml in stroke volume and an increase of 0.7 l/min/m² in cardiac
index were found. When compared with placebo, levosimendan
caused a significantly higher positive haemodynamic response
at the sixth hour (17% with placebo, 80% with levosimendan).
Symptomatic improvement in patients has been found to
be parallel to haemodynamic improvement. Folloth
et al
.
demonstrated that positive haemodynamic responses continued
for 24 hours following discontinuation of the infusion.
14
In our study, cardiac output and cardiac index values in
the levosimendan group were significantly lower compared
to the control group. Cardiac output and cardiac index in the
levosimendan group also showed remarkable increases compared
to the control group. In patients receiving levosimendan, at the
end of the 24th hour, an increase of approximately 2.9 l/min in
cardiac output and an increase of approximately 2 l/min/m
2
in
cardiac index were found. In the control group, at the end of
the 24th hour, this increase remained limited to approximately
0.7 l/min in cardiac output and 0.3 l/min/m
2
in cardiac index.
Correspondingly, Tachibana
et al
. showed that levosimendan
improved left ventricular systolic and diastolic performance at
rest and during exercise after heart failure.
15
In our study, we also examined pulmonary arterial pressure,
pulmonary vascular resistance and systemic vascular resistance
in order to determine the vasodilatatory effect of levosimendan.
When considered individually, initial values of mean pulmonary
arterial pressure were found to be significantly higher in the
levosimendan group. At the end of the 24th hour, a marked
decrease in the pulmonary arterial pressure was observed in the
levosimendan group, but the decrease in the control group was
not significant.
A marked decrease in pulmonary vascular resistance values
was also recorded in favour of levosimendan at the end of the
24th hour. These results were consistent with those of Lilleberg
et
al
., who found that levosimendan decreased pulmonary vascular
resistance early after CABG.
16
Systemic vascular resistance
values showed marked decreases in both the levosimendan and
control groups.
Pre-operative cardiac output values in the levosimendan group
were less than those of the control group, whereas pulmonary
vascular resistance and pulmonary pressure values measured
by thermodilution catheter were significantly higher compared
to the control group. Despite these values, this patient group
was easily weaned from CPB and the postoperative period went
smoothly. This patient group was discharged with a full recovery.
More significant results were obtained from the levosimendan
group compared to the control group regarding increases in
postoperative CO and CI, and decreases in PVR and PAP values.
Based on the published literature mentioned above, we expected
that greater preservation of cardiac function after CPB would
result in a better recovery. Our results were consistent with
these findings. This indicates that levosimendan was beneficial.
However, when clinical results were considered, no difference in
favour of levosimendan was determined regarding the mortality
and morbidity rates between the groups.
The most common adverse reactions with levosimendan
include headache, dizziness, hypotension, ventricular tachycardia,
atrial fibrillation, tachycardia, ventricular extrasystoles, cardiac
failure, myocardial ischaemia, extrasystoles, nausea, vomiting,
constipation, diarrhoea, insomnia, decreased haemoglobin and
hypokalaemia. There was no significant adverse effect from the
drug in our study group.
When the groups were compared with regard to risk scoring
(EuroSCORE), they were found to be similar. On the other hand,
the pre-operative CO and CI values were lower and the PVR and
PAP values were higher in the levosimendan group, but it will
be noted that this was a more high-risk group. Despite this, this
group could easily be weaned from CPB and discharged with a
full recovery.
In our study, patients in the levosimendan group were
discharged later than the control group, contrary to results in
