Mini Review

Levosimendan and Acute Kidney Injury


Burcu Tanay Demirdöven, Mehmet Çağatay Gürkök, Yasin Levent Uğur and Uğur Koca*

1Buca Seyfi Demirsoy Hospital Emergency Medicine, Turkey

2Dokuz Eylül University School of Medicine Anesthesiology and Reanimation Department, Intensive Care Unit, Turkey
3Dokuz Eylül University School of Medicine Anesthesiology and Reanimation Department, Intensive Care Unıt
4Dokuz Eylul University School of Medicine Department of Anesthesiology and Reanimation, Intensive Care Unit, Turkey

Received Date: 18/06/2020; Published Date: 09/07/2020


*Corresponding author: Özgür Oğul Koca, Business administration, University of Economics, İzmir, Turkey

 DOI: 10.46718/JBGSR.2020.03.000062

Cite this article: Özgür Oğul Koca, Levosimendan and Acute Kidney Injury. Op Acc J Bio Sci & Res 3(1)-2020.

Keywords: Levosimendan; Acute; Kidney

Mini Review

Severe sepsis is one of the most common causes of death in intensive care units, while in the presence of septic shock, the mortality rate reaches approximately 70% despite the progress made in the care of critical patients [1]. The widespread inflammatory and procoagulant response caused by sepsis leads to diffuse endothelial dysfunction, endovascular damage, and eventually multiple organ failure. Sepsis, ischemia reperfusion damage, toxic nephropathy, hypovolemia and urinary system obstruction can cause acute renal failure (ARF). However, it was experimentally observed that medullary and cortical blood flow in septic ARF continued or even increased, and this was described as a completely different physiological event from ABY which was not due to sepsis [2].

Major systemic and local mediators, neutrophil-endothelial interactions, microvascular thromboses, renal hypoperfusion, and reperfusion damage have been blamed for the pathogenesis of acute renal failure. Norepinephrine, angiotensin II and vasopressin are important systemic mediators in sepsis. Local mediators, especially tumor necrosis factor (TNF) or interleukin 1 (IL-1), adhesion molecules, oxygen free radicals, catalyzes the if A2(TXA2), prostaglandin E2(PGE2), leukotrienes, platelet-induced growth factor, endothelin, nitric oxide(no) and adenosine include [3]. Nearly half of patients with acute kidney damage (AKD) have sepsis, while in intensive care units, AKD is accompanied by more septic shock. Mortality is higher in patients with sepsis-induced AKD. Adequate fluid replacement, early renal replacement therapy are useful for patients, but there is no method to treat septic AKD [4].


If hypotension cannot be corrected despite fluid resuscitation in sepsis treatment, vasopressor therapy is recommended [5]. Dopamine and norepinephrine were the first vasopressors to be selected in the treatment of Sepsis and septic shock [6]. Levosimendan is a new inotropic and vasodilator agent that has been proven to be beneficial, especially in patients with acute heart failure and acute coronary syndrome. [7]. It opens ATP - sensitive potassium channels in vascular smooth novellas cells, causing arteriolar-venous dilation. This mechanism of action is responsible for coronary, pulmonary, renal and systemic vasodilation [8,9]. In addition to blood urea nitrogen and creatinine, new and specific methods such as cystatin c, neutrophil gelatinase associated lipocalin (NGAL)], IL-8, kidney damage molecule [Kidney Injury Molecule(KIM)]-1 have been introduced in recent years to show acute kidney damage [10].


Neutrophil gelatinase associated lipocalin has been reported as the earliest and most reliable laboratory parameter showing renal ischemia or nephrotoxicity in humans, especially in kidney, lung, stomach and colon cells [11]. NGAL levels can be detected in both urine and plasma within 2-6 hours after AKD [12]. Law et al. [13] they showed that levosimendane reduces tubular necrosis and atrophy in experimental renal ischemia reperfusion damage. However, the study examining the effect of levosimendan on acute kidney damage in polymicrobial sepsis model induced by cecal ligation perforation method was not reached.


1. Pinto BB, Rehberg S, Ertmer C, Westphal M (2008) Role of levosimendan in sepsis and septic shock. Curr Opin Anesthesiol 21: 168-177.
2. Jacobs R, Honore PM, Joannes-Boyau (2011) Septic acute kidney ınjury: the culprit is inflammatory apoptosis rather than ischemic necrosis. Blood Purif 32: 262-265.
3. Lee T, Xu H, Siegel CD, Krichevsky IE (2003) Local anesthetics ınduce human renal cell apoptosis. Am J Nephrol 23: 129–139.
4. Yasuda H (2006) Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects. Kidney Int 69(9): 1535-1542.
5. Levy B, Bolaert PE, Carpentier C (1997) Comparison of norepinephrine and dobutamine to epinephrine for heamodynamics, lactate metabolism, and gastric tonometric variables in septic shock: A prospective, randomized study. İntensive Care Med 23: 282-287.
6. Rehberg S, Ertmer C, Vincent JL (2010) Effects of combined arginine vasopressin and levosimendan on organ function in ovine septic shock. Crit Care Med 38: 2016–2023.
7. Harjola VP, Oikarinen L, Toivonen L, Jurkko R (2008) The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimenda and digoxin in patients with NYHA Classes II-III hearth failure. Int J Clin Pharmacol Ther 46: 389-399.
8. Lasse A, Lehtonen J, Antila S (2004) Pharmacokinetics and pharmacodynamics of ıntravenous ınotropic agents. Clin Pharmacokinet 43(3): 187-203.
9. Figgitt DP, Gillies SP, Karen L (2001) Goa, New drug file:Levosimendan Drugs 61(5): 613-627.
10. Lisowska-Myjak B (2010) Serum and urinary biomarkers of acute kidney injury. Blood Purif 29: 357-365.
11. Nguyen Mai T, Devarajan P (2008) Biomarkers for the early detection of acute kidney injury. Pediatr Nephrol 23: 2151-2157.
12. Mishra J, Dent C, Tarabishi R, Mitsnefes MM (2005) Neutrofil gelatinase-associated lipocalin(NGAL) as a biomarkır for acute renal injury following cardiac surgery Lancet 365: 1231-1238.
13. Yakut N, Yasa H (2008) The influence of levosimendan and iloprost on renal ischemia-reperfusion: an experimental study. İnteract Cardiovasc Thorac Surg 7: 235-239.

Mechanical ventilators control either gas flow (volume control) or airway pressure (pressure control) for the inspiratory period. Dual control modes are designed to combine the constant minute ventilation of volume control ventilation and the fast variable current advantages of pressure control ventilation. All dual control modes provide pressure controlled breath using pressure limit and descending flow model. The volume produced varies depending on the patient's effort and pulmonary impedance. In the dual control mode, unlike the pressure control mode, the output is changed according to the measured input (volume). Dual control modes can be patient or time triggered, current or time cycled.


Dual Control modes allow you to set the volume target while the ventilator is pressure controlled breathing. In dual-in-breath mode, the ventilator switches from volume control to volume control, according to the patient's inspiratory effort and ability to reach the set minimum tidal volume, within the same breath. While the device is working in pressure support (PS) or pressure control (PC) mode in breathless dual control mode, with the operation of the feedback ring, it decreases or increases the pressure limit to provide the tidal volume set by the clinician.