Alberto Zangrillo1, Alessandro Putzu2, Fabrizio Monaco3, Alessandro Oriani4, Giovanna Frau5, Monica De Luca6, Nora Di Tomasso7, Elena Bignami8, Vladimir Lomivorotov9, Valery Likhvantsev10, Giovanni Landoni11. 1. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University of Milan, Milan, Italy. Electronic address: zangrillo.alberto@hsr.it. 2. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: alessandroputzu@ymail.com. 3. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: monaco.fabrizio@hsr.it. 4. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: oriani.alessandro@hsr.it. 5. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: frau.giovanna@hsr.it. 6. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: monica.deluca@libero.it. 7. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: noramed@hotmail.it. 8. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: bignami.elena@hsr.it. 9. Department of Anesthesiology and Intensive Care, State Research Institute of Circulation Pathology, Novosibirsk, Russia. Electronic address: vvlom@mail.ru. 10. Anesthesiology & Intensive Care Department, Moscow Regional Clinical & Research Institute, Moscow, Russia. Electronic address: lik0704@gmail.com. 11. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University of Milan, Milan, Italy. Electronic address: landoni.giovanni@hsr.it.
Abstract
PURPOSE: There is controversy about the use of inotropes in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate if levosimendan, as compared with standard inotropic therapy (eg, dobutamine), reduces mortality in septic patients. MATERIALS AND METHODS: BioMedCentral, PubMed, EMBASE, and the Cochrane Central Register were searched for pertinent studies, up to 1st May 2015. Randomized trials on the use of levosimendan in patients with severe sepsis and septic shock were included if reporting mortality data. The primary outcome was mortality, whereas secondary outcomes were blood lactate, cardiac index, total fluid infused, norepinephrine dosage, and mean arterial pressure. RESULTS: Seven studies for a total of 246 patients were included in the analysis. Levosimendan was associated with significantly reduced mortality compared with standard inotropic therapy (59/125 [47%] in the levosimendan group and 74/121 [61%] in the control group; risk difference = -0.14, risk ratio = 0.79 [0.63-0.98], P for effect = .03, I(2) = 0%, numbers needed to treat = 7). Blood lactate was significantly reduced in the levosimendan group, whereas cardiac index and total fluid infused were significantly higher in the levosimendan group. No difference in mean arterial pressure and norepinephrine usage was noted. CONCLUSIONS: In patients with severe sepsis and septic shock, levosimendan is associated with a significant reduction in mortality compared with standard inotropic therapy. A large ongoing multicenter randomized trial will have to confirm these findings.
PURPOSE: There is controversy about the use of inotropes in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate if levosimendan, as compared with standard inotropic therapy (eg, dobutamine), reduces mortality in septicpatients. MATERIALS AND METHODS: BioMedCentral, PubMed, EMBASE, and the Cochrane Central Register were searched for pertinent studies, up to 1st May 2015. Randomized trials on the use of levosimendan in patients with severe sepsis and septic shock were included if reporting mortality data. The primary outcome was mortality, whereas secondary outcomes were blood lactate, cardiac index, total fluid infused, norepinephrine dosage, and mean arterial pressure. RESULTS: Seven studies for a total of 246 patients were included in the analysis. Levosimendan was associated with significantly reduced mortality compared with standard inotropic therapy (59/125 [47%] in the levosimendan group and 74/121 [61%] in the control group; risk difference = -0.14, risk ratio = 0.79 [0.63-0.98], P for effect = .03, I(2) = 0%, numbers needed to treat = 7). Blood lactate was significantly reduced in the levosimendan group, whereas cardiac index and total fluid infused were significantly higher in the levosimendan group. No difference in mean arterial pressure and norepinephrine usage was noted. CONCLUSIONS: In patients with severe sepsis and septic shock, levosimendan is associated with a significant reduction in mortality compared with standard inotropic therapy. A large ongoing multicenter randomized trial will have to confirm these findings.
Authors: Anders Perner; Anthony C Gordon; Daniel De Backer; George Dimopoulos; James A Russell; Jeffrey Lipman; Jens-Ulrik Jensen; John Myburgh; Mervyn Singer; Rinaldo Bellomo; Timothy Walsh Journal: Intensive Care Med Date: 2016-10-01 Impact factor: 17.440