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Case
Report
Levosimendan in a neonate with
severe coarctation of aorta and low
cardiac output syndrome
Yann Olivier Boegli1,2, Simone Gioanni1, Mathieu van Steenberghe3,4, Philippe Pouard1
Departments of Pediatric Cardiac Anesthesiology and Intensive Care, 3Pediatric Cardiac Surgery, Necker‑Sick Children
Hospital, Paris, France, 2Anesthesiology and 4Cardiovascular Surgery, University Hospital Centre, Lausanne, Switzerland
1
ABSTRACT
Received: 03‑12‑12
Accepted: 28‑04‑13
We report successful use of levosimendan after failed balloon angioplasty in a critically ill neonate with
coarctation of aorta (CoA) and severe low cardiac output syndrome (LCOS). Treatment with levosimendan
improved left heart function, and decreased lactate and brain natriuretic peptide levels. To our knowledge,
this is the first report on the safe and successful use of levosimendan in the management of LCOS due to
severe CoA in a neonate awaiting surgical repair.
Key words: Coarctation of aorta, Balloon angioplasty, Brain natriuretic peptide, Levosimendan, Low cardiac
output syndrome
INTRODUCTION
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DOI:
10.4103/0971-9784.114254
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Coarctation of the aorta (CoA) represents 5‑7%
of congenital heart diseases with an incidence
of 0.3‑0.4 per 1000 live births.[1] Cardiac failure
with metabolic acidosis and multiorgan
dysfunction is a major cause of death in
these patients which may be attributed
to premature closure of the patent ductus
arteriosus (PDA). Prostaglandins are the first
line pharmacologic agent in the management
of CoA; however, in the neonates, response
to them is unpredictable.[2] In these critical
situations, the outcome is often unfavourable
unless the aortic obstruction is released as
soon as possible by angioplasty or by surgical
repair.[3] We describe the use of levosimendan
after failure of balloon angioplasty for CoA in
a neonate complicated by low cardiac output
syndrome (LCOS) awaiting surgical repair.
CASE REPORT
A 9-day-old, 3.5 kg, term‑born child was
referred to the emergency room for poor
feeding. On clinical examination, the baby
was lethargic and the femoral pulses were
absent. Transthoracic echocardiography (TTE)
showed a severely hypokinetic left ventricle
corresponding to LCOS due to severe CoA
(ejection fraction < 20%). During TTE, a small
PDA with a bidirectional shunt was also
identified. The X‑ray chest showed an enlarged
heart [Figure 1]. The patient was transferred
to the intensive care unit. Arterial blood gas
analysis showed metabolic acidosis with a
pH 7.13 and lactate 15 mmol/l; the child was
oligo‑anuric. The liver function test showed
elevated L‑aspartate aminotransferase 75 U/l;
and L‑aspartate aminotransferase 224 U/l. After
placement of a central venous and an arterial
catheter (arterial pressure −42/25 mmHg),
the child was intubated and ventilated using
FiO2: 50%, positive end‑expiratory pressure
PEEP: 8 cmH2O, respiratory rate: 35/min; the
peak inspiratory airway pressure was 23 mmHg;
simultaneously, an infusion of alprostadil
25 ng/kg/min and epinephrine 0.05 µg/kg/
min was started. In spite of support with
epinepherine and the increase of prostaglandin
dose, the pH was 7.38 and the lactate and
NT‑proBNP (N‑terminal pro‑B‑type natriuretic
peptide) levels were high at 20 mmol/l and
> 5000 pg/ml, respectively. A repeat TTE was
Address for correspondence: Dr. Yann Olivier Boegli, Department of Paediatric Cardiac Anaesthesiology and Intensive Care, Necker – Sick Children
Hospital, Paris, France and Department of Anaesthesiology, University Hospital Centre, Lausanne, Switzerland. E‑mail: [email protected]
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Boegli, et al: Levosimendan in a neonate with severe coarctation
performed, which showed a hypokinetic left ventricle
with an ejection fraction (LVEF) less than 30%. Gradient
across the CoA was high in spite of heart failure (gradient
max: 38 mmHg). Balloon angioplasty was attempted in
the catheterization laboratory, but was unsuccessful
because the angioplasty catheter could not be passed
beyond the stenosis. The left ventricular function did
not improve (gradient max: 32 mmHg and LVEF < 30%).
BNP remained at 5000 pg/ml while lactate decreased
to 13 mmol/l. Then, an infusion of levosimendan
0.2 µg/kg/min was started and epinepherine infusion
was weaned. The treatment with alprostadil was
continued until surgery to maintain patency of the PDA.
After 24 h of levosimendan infusion an improvement of
the left heart function (LVEF 58%) was observed with
a decrease of the lactate and BNP levels to 1.8 mmol/l
and to 508 pg/ml, respectively [Figure 2]. Urine output
and liver functions also improved.
Two days after admission in the paediatric intensive
care unit (PICU), a Crafoord procedure (excision of CoA
segment and end‑to‑end anastomosis) was successfully
performed. Nevertheless, the BNP level increased to
5000 pg/ml in spite of the clinical improvement. The
child was extubated 23 h after surgery and left the
PICU 3 days later. Follow‑up TTE showed a LVEF of
72%. The BNP and lactate levels decreased to 2470 pg/
ml and 1.5 mmol/l.
of CoA complicated with LCOS remains debatable.[4]
In our center, in neonates with CoA and LCOS, the
initial treatment is to attempt balloon angioplasty in
the catheterization laboratory. Because of failed balloon
angioplasty, we started levosimendan as a bridge
to surgical repair. In France, nominative temporary
authorization for the off‑label use of levosimendan
is granted by the national agency of drugs safety
(Agence National de Sécurité du Médicament et des
Produits de Santé). Levosimendan was preferred
over milrinone because of its more pronounced
inotropic effects and for its anti‑stunning and
anti‑ischemic properties.[5] Furthermore, because of its
calcium‑sensitizing properties, levosimendan is an ideal
therapeutic for the immature myocardium, characterized
by a highly calcium‑dependent contractility.[6,7] The
administration of levosimendan in paediatric patients
has been described since 2004. In the neonatal
population; however, only a few case reports discuss
the use of levosimendan for heart failure, pulmonary
hypertension or after cardiac surgery. The improvement
of left‑ventricular function was highlighted and no
side‑effects were reported in these isolated cases.[8,9]
Nevertheless, no controlled clinical trial exist to verify
this observation. Based on our report, we propose the
use of levosimendan as cardiac conditioning agent
before surgery in the neonates presenting with severe
CoA and acute left‑ventricular failure. We believe that
DISCUSSION
The present case report underscores the successful
use of levosimendan in a critically ill neonate with
CoA and severe LCOS. The severity of the cardiac
failure was documented by echocardiography and by
NT‑proBNP and lactate levels. The initial management
Figure 1: Chest X‑ray at admission, showing moderate cardiomegaly
Annals of Cardiac Anaesthesia  Vol. 16:3  Jul-Sep-2013
Figure 2: Trends of lactatemia and N‑terminal pro‑B‑type natriuretic peptide
level at baseline, after balloon angioplasty, after treatment with levosimendan,
and after surgery
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Boegli, et al: Levosimendan in a neonate with severe coarctation
the favorable properties of the levosimendan (positive
inotropism, peripheral vasodilatation, preservation
of the consumption of oxygen) could be useful in
these conditions. In our patient, the efficacy of the
treatment was assessed by repeated echocardiography
and assessment of biomarkers NT‑proBNP and lactate
as markers of cardiac failure and multiorgan failure.
In this case, we noted that the level of BNP correlated
with the clinical observations as well as with the
echocardiographic findings. After the failed attempt
at balloon dilatation, BNP did not decrease and the
ventricular and multiorgan dysfunction persisted. After
12 h, of the onset of treatment with levosimendan,
the significant fall in BNP was accompanied with an
improvement of cardiac function with a LVEF reaching
58% on TTE. The drop in lactate and the progressive
restoration of diuresis also correlated with the efficacy
of levosimendan treatment. After 24 h of treatment
with levosimendan, and stabilization of the clinical
status, the child was successfully operated. During the
procedure, we observed an increase of NT‑proBNP. It
has been shown that the level of NT‑proBNP increases
significantly 6 h after surgery for congenital heart
diseases, to reach a plateau between 12 h and 48 h.[10,11]
However, these studies only concern cardiac surgery
using the cardiopulmonary bypass (CPB) and their
results may not be applicable for surgery without CPB.
We, however, extrapolated these conclusions in view
of the aortic cross clamping during the surgical repair
of CoA.
CONCLUSION
Neonates presenting for emergency surgery with LCOS
and multiorgan failure are prone to an increased rate of
adverse outcome. Levosimendan is an inodilator and
doesn’t increase myocardial oxygen consumption. It
is a myofilament calcium sensitizer without alpha or
beta receptor agonist effects. It allows decreasing beta
adrenergic inotropes, and may induce pharmacological
pre‑conditioning. In this neonate, myocardial recovery
assessed by echocardiography, blood lactate and
214
NT‑proBNP levels showed gradual recovery of
myocardial function during the levosimendan treatment.
No side‑effects were noticed during the levosimendan
administration. Although controlled trials concerning
the safety of levosimendan in neonates have not yet
been performed, we suggest its cautious use as a
bridge to surgery in neonates with a LCOS due to CoA.
Prospective trials are needed to confirm our findings.
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Cite this article as: Boegli YO, Gioanni S, van Steenberghe M, Pouard P.
Levosimendan in a neonate with severe coarctation of aorta and low cardiac
output syndrome. Ann Card Anaesth 2013;16:212-4.
Source of Support: Nil, Conflict of Interest: None declared.
Annals of Cardiac Anaesthesia  Vol. 16:3  Jul-Sep-2013