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Levosimendan in myocardial depression due to severe sepsis
Critical Care volume 11, Article number: P226 (2007)
Myocardial depression in sepsis, among other factors, is due to calcium (Ca2+) desensitization in the myofilament. So using a Ca2+ sensitizer drug may play a beneficial role in this situation. Levosimendan has a dual mechanism; it causes Ca2+ sensitization through binding to Troponin C and opening of ATP-dependent K+ channels in vascular smooth muscle.
A prospective observational case-series study extending over a period of 18 months from November 2004 to April 2006. We analyze the data of 18 patients receiving levosimendan for myocardial depression due to severe sepsis and compare them with our historical data in the previous year of the same group of patients regarding mortality. All those patients were included in the study who had a pulmonary artery catheter (PAC) and who after initial resuscitation (early goal-directed therapy (EGDT)) did not respond to treatment and their cardiac index (CI) was <2.2. Each patient than received an infusion of levosimendan at 0.1 μg/kg/min without a loading dose. Hemodynamic parameters such as the CI, mixed venous saturation (SvO2) and mean arterial pressure (MAP) were recorded at 0, 12, 24 and 48 hours. Noradrenaline was used to maintain a MAP above 65 mmHg. Patients were followed for 30 days to document the 7th-day and 30th-day mortality. SPSS 11 was used for statistical analysis. The Student t test was used as a test of significance.
The average age was 67.6 ± 10.39 years and the APACHE II score was 26.33 ± 2.37. Patients were divided into three subgroups: survivors, 7th-day and 30th-day mortality groups. There was no significant difference in these subgroups regarding age and APACHE II score. Levosimendan group 7th-day and 30th-day mortality was 33% and 66% as compared with historical data of 37% and 71%, respectively. The change in CI in the survivor group was significant (P = 0.021), from 2.11 ± 0.17 to 3.8 ± 0.28, while in the 7th-day and 30th-day mortality groups it was insignificant. SvO2 increased in the survivor and 30th-day mortality groups significantly (P = 0.011 and P = 0.035, respectively). It did not show any significant improvement in the other group. MAP also showed significant improvement in the survivor group (P = 0.026) and insignificant in others.
It is evident from our study that levosimendan improves hemodynamic response in septic patients. Although it improves the mortality, we cannot say with full confidence that these improved hemodynamic parameters are responsible. Randomised control trials are needed to answer this question, which are underway.
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Malik, M., Mandourah, Y. Levosimendan in myocardial depression due to severe sepsis. Crit Care 11, P226 (2007). https://doi.org/10.1186/cc5386
- Severe Sepsis
- Mean Arterial Pressure
- Cardiac Index
- Septic Patient
- Hemodynamic Parameter