Objective: To evaluate the effects of levosimendan on hemodynamics and cardiac function in patients with septic shock.
Methods: A prospective single-center randomized controlled trial was conducted. The patients with septic shock admitted to the Department of Critical Care Medicine of the Third Hospital of Hebei Medical University from June 2011 to October 2013 were enrolled. The patients with septic shock received the conventional treatment according to international guidelines for management of severe sepsis and septic shock. Thirty-six patients received the examination of echocardiography and left ventricular ejection fraction (LVEF)≤ 0.45 after fluid resuscitation were enrolled the study, who were divided into two groups according to random number table, with 18 cases in each group. After the conventional treatment, the patients in dobutamine group received intravenous injection of 5 μg × kg⁻¹ min⁻¹ dobutamine for 48 hours immediately after fluid resuscitation, and those in levosimendan group received a 24-hour infusion of 5 μg × kg⁻¹ min⁻¹ dobutamine followed by a 24-hour infusion of 0.2 μg × kg⁻¹ × min⁻¹ levosimendan. The hemodynamics and cardiac function were evaluated by pulse indicator continuous cardiac output (PiCCO) and ultrasound during treatment.
Results: Compared with dobutamine group, after the treatment in the levosimendan group, stroke volume index (SVI), cardiac index (CI) and left ventricular stroke work index (LVSWI) were significantly increased [SVI (mL/m²): 39.8 ± 5.4 vs. 37.5 ± 4.5, t=-2.762, P=0.020; CI (L × min⁻¹ × m⁻²): 4.6 ± 0.7 vs. 3.6 ± 0.7, t=-9.829, P=0.000; LVSWI (kg ×min⁻ ¹ m⁻²): 33.7 ± 2.4 vs. 28.2 ± 1.2, t=-6.307, P=0.000], and central venous pressure (CVP), intrathoracic blood volume index (ITBVI) and extravascular lung water index (EVLWI) were significantly decreased [CVP (mmHg, 1 mmHg=0.133 kPa): 8.2 ± 0.9 vs. 12.1 ± 0.8, t=3.928, P=0.002; ITBVI (mL/m²): 820 ± 42 vs. 978 ± 69, t=9.472, P=0.000; EVLWI (mL/kg): 6.1 ± 1.6 vs. 8.9 ± 1.7, t=4.467, P=0.001]. Cardiac ultrasound showed that compared with dobutamine group, in the levosimendan group, left ventricular end-systolic volume (LVESI) and end-diastolic volume (LVEDI) were significantly lowered [LVESI (mL/m²): 32.7 ± 9.2 vs. 48.2 ± 13.4, t=0.882, P=0.000; LVEDI (mL/m²): 61.7 ± 11.4 vs. 78.6 ± 13.6, t=2.453, P=0.032], and the LVEF was significantly increased (0.463 ± 0.068 vs. 0.383 ± .085, t=-2.439, P=0.035). Levosimendan also could decrease the lactic acid (mmol/L: 3.4 ± 1.1 vs. 5.2 ± 1.2, t=3.346, P=0.007), and increase the lactate clearance rate (mL/min: 73.2 ± 13.5 vs. 47.6 ± 11.8, t=-4.079, P=0.002), 24-hour urinary output (mL: 2 213.4 ± 354.0 vs. 1 533.8 ± 402.0, t=6.342, P=0.000) and 24-hour cumulative intake (mL: 5 746.6 ± 420.0 vs. 4 156.7 ± 215.0, t=7.126, P=0.000). There were no significant differences in total volume of norepinephrine,mortality in intensive care unit (ICU) and 28-day mortality between two groups.
Conclusions: Levosimendan can increase cardiac ejection function, reduce the heart blood and vascular preload, intrathoracic lung water, improve heart function and systemic hemodynamic indexes of patients with septic shock.