Intensive Care Medicine

, Volume 31, Issue 1, pp 164–165

Levosimendan in septic cardiac failure

Authors

  • A. Noto
    • Istituto di Anestesiologia e Rianimazione dell’Università degli Studi di MilanoAzienda Ospedaliera-Polo Universitario San Paolo
  • M. Giacomini
    • Istituto di Anestesiologia e Rianimazione dell’Università degli Studi di MilanoAzienda Ospedaliera-Polo Universitario San Paolo
  • A. Palandi
    • Istituto di Anestesiologia e Rianimazione dell’Università degli Studi di MilanoAzienda Ospedaliera-Polo Universitario San Paolo
  • L. Stabile
    • Istituto di Anestesiologia e Rianimazione dell’Università degli Studi di MilanoAzienda Ospedaliera-Polo Universitario San Paolo
  • C. Reali-Forster
    • Istituto di Anestesiologia e Rianimazione dell’Università degli Studi di MilanoAzienda Ospedaliera-Polo Universitario San Paolo
    • Istituto di Anestesiologia e Rianimazione dell’Università degli Studi di MilanoAzienda Ospedaliera-Polo Universitario San Paolo
Correspondence

DOI: 10.1007/s00134-004-2502-3

Cite this article as:
Noto, A., Giacomini, M., Palandi, A. et al. Intensive Care Med (2005) 31: 164. doi:10.1007/s00134-004-2502-3

Cardiac failure in septic shock is not always corrected by vasoactive-inotropic drugs and fluid therapy [1]. Levosimendan is a new inodilator for primitive cardiac failure acting by sensitising troponin-C to calcium and opening the adenosine-triphosphate-sensitive potassium channels. In addition, it has phosphodiesterase-inhibiting properties [2]. Animal data (in vitro [2] and pre-treatment in vivo [3]) showed a positive effect when used in septic shock, as well as in different types of shock in humans, some of which were septic [4]. The drug’s mode of action in septic cardiac failure could also be different from calcium sensitivity [2].

We used levosimendan in two cases of septic shock with cardiac failure unresponsive to standard treatment (Table 1). Patient A was a 26-year-old, previous healthy female, admitted in shock due to bacterial pneumonia. Day 1: mechanical ventilation, fluid loading and continuous infusion of vasopressors improved the hemodynamic status but myocardial competence was getting worse with anuria, gut ischemia, intestinal bleeding, and cutaneous necrosis (Day 2).
Table 1

Best hemodynamic parameters found in the selected days in patient A and B. Days 1–2: standard septic-shock therapy. Day 3: before levosimendan infusion (pre-) and during 24-h treatment. Day 8 (patient A), day 6 (patient B): withdrawal of amine infusion. (NE norepynephrine, DB dobutamine).

Patient A

Day

Vasoactive Drugs

HR

MAP

CVP

PAPm

WP

SvO2

CI/SI

SVR

Shunt

Lactate

pH

(bpm)

(mmHg)

(mmHg)

(mmHg)

(mmHg)

(%)

(l·min·m2)/(ml/m2)

(dyne·s/cm5·m2)

(%)

(mmol/l)

1

NE 12 μg/min

143

59

14

28

19

75

4. 7/33

497

48

4. 6

7. 36

DB 10 μg·kg·min

2

NE 10 μg/min

108

56

22

29

25

50

1. 9/17

850

20

7

7. 35

DB 12 μg·kg·min

3 (pre-

NE 10 μg/min

106

60

22

28

25

51

2. 1/19

948

18

6. 6

7. 35

DB 12 μg·kg·min

3 (2 h)

NE 8 μg/min

110

60

15

26

22

61

2. 6/23

900

22

5. 7

7. 37

DP 12 μg·kg·min

3 (6 h)

NE 8 μg/min

114

63

14

23

14

67

3. 1/27

765

24

4. 8

7. 38

DP 11 μg·kg·min

3 (12 h)

NE 3 μg/min

116

65

18

25

19

63

2. 6/24

857

22

1. 6

7. 39

DP 10 μg·kg·min

3 (18 h)

NE 3 μg/min

106

71

16

24

19

70

3. 4/32

692

22

1. 4

7. 41

DB 8 μg·kg·min

8

Stop

91

71

15

23

16

74

3. 5/38

726

19

0. 9

7. 4

Patient B

Day

Vasoactive Drugs

HR

MAP

CVP

PAPm

WP

SvO2

CI/SI

SVR

Shunt

Lactate

pH

(bpm)

(mmHg)

(mmHg)

(mmHg)

(mmHg)

(%)

(l/min·m2)/(ml/m2)

(dyne·s/cm5·m2)

(%)

(mmol/l)

1

NE 30 μg/min

125

50

15

33

21

63

2. 6/20

620

14

7. 4

7. 37

DB 6 μg/kg/min

2

NE 15 μg/min

128

51

21

30

26

66

2. 9/24

413

8

5. 5

7. 47

DB 10 μg/kg/min

3 (pre-)

NE 15 μg/min

105

54

18

31

24

65

3. 0/29

523

7

5. 1

7. 44

DB 10 μg/kg/min

3 (2 h)

NE 15 μg/min

104

57

14

26

23

75

3. 3/31

531

10

1. 4

7. 46

DB 5 μg/kg/min

3 (6 h)

NE 15 μg/min

100

62

17

26

21

75

3. 8/38

466

13

0. 6

7. 47

DB 4 μg/kg/min

3 (12 h)

NE 15 μg/min

103

64

19

28

21

74

3. 9/38

440

11

0. 9

7. 40

DB 4 μg/kg/min

3 (18 h)

NE 12 μg/min

95

61

15

25

17

70

3. 8/40

479

9

0. 8

7. 41

6

Stop

99

67

8

24

15

76

3. 9/39

615

7

0. 6

7. 45

Patient B was a 79-year-old male, with dilated cardiomyopathy, admitted in shock due to acute cholangitis. Day 1: despite mechanical ventilation, fluid loading and continuous infusion of vasopressors, a severe hypo-dynamic state was present. Day 2: we tried to adjust vasopressor dosages without significant clinical change. In both cases, on day 3, a loading dose of levosimendan (12 μg/kg, but not in patient B because of atrial fibrillation at high frequency) followed by a 24-h continuous infusion at 0.1 μg·kg·min was administered.

A clinical improvement of shock was recorded at 2 h of levosimendan administration. There was improvement of pulmonary venous oxygen saturation and a decline in serum lactate levels. The peak of the hemodynamic effect was reached between 6–18 h allowing a concomitant decrease of vasoactive dosages until suspension on days 8 and 6 respectively, strongly suggesting a causal relationship. Of note, there was a trend toward pulmonary artery decrease as suggested by experimental data [3], not associated with worsening of pulmonary shunt. Patient A died from brain haemorrhage on day 23 after resolution of septic shock and severe pneumonia. Patient B was discharged to the ward after 14 days.

Our report confirms the effectiveness of levosimendan in human septic shock [4], supporting a potential application in a definite scenario (severe septic cardiac failure) and timing (unresponsiveness to standard therapy).

Copyright information

© Springer-Verlag 2004