Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression.
OBJECTIVE
Calcium desensitization plays an important part in the pathophysiology of septic myocardial depression. We postulated that levosimendan, a new calcium sensitizer, would be beneficial in sepsis-induced cardiac dysfunction.


METHODS
Prospective, randomized, controlled study in two university hospital intensive care units.


METHODS
Twenty-eight patients with persisting left ventricular dysfunction related to septic shock after 48 h of conventional treatment including dobutamine (5 microg/kg per minute).


METHODS
After 48 h of conventional treatment patients were randomized to receive a 24-h infusion of either levosimendan (0.2 microg/kg per minute, n=15) or dobutamine (5 microg/kg per minute, n=13).


RESULTS
Data from right heart catheterization, echocardiography, gastric tonometry, laser-Doppler flowmetry, and lactate concentrations and creatinine clearance were obtained before and after the 24-h drug infusion. Dobutamine did not change systemic or regional hemodynamic variables. By contrast, at the same mean arterial pressure levosimendan decreased pulmonary artery occlusion pressure and increased cardiac index. Levosimendan decreased left ventricular end-diastolic volume and increased left ventricular ejection fraction. Levosimendan increased gastric mucosal flow, creatinine clearance, and urinary output while it decreased lactate concentrations.


CONCLUSIONS
These findings show that levosimendan improves systemic hemodynamics and regional perfusion in patients with septic cardiac dysfunction under conditions where administration of 5 microg/kg dobutamine per minute is no longer efficacious. Accordingly, our results suggest that levosimendan can be an alternative to the strategy of increasing the dose of dobutamine under such conditions.
Morelli
Andrea
A
Department of Anesthesiology and Intensive Care, University of Rome La Sapienza, Rome, Italy. andrea.morelli@uniroma1.it
De Castro
Stefano
S
Teboul
Jean-Louis
JL
Singer
Mervyn
M
Rocco
Monica
M
Conti
Giorgio
G
De Luca
Leonardo
L
Di Angelantonio
Emanuele
E
Orecchioni
Alessandra
A
Pandian
Natesa G
NG
Pietropaoli
Paolo
P
D002303:Cardiac Output, Low / Q000188:drug therapy*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D012772:Shock, Septic / Q000188:drug therapy*; D000077464:Simendan; D018709:Statistics, Nonparametric
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan