{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:20:20Z","timestamp":1760059220105,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Septic patients can show multiorgan failure even after an apparent recovery of hemodynamic stability. The underlying mechanism is unclear, but the main pathological element is microcirculation impairment, leading to insufficient oxygen delivery. This study aimed to assess the effects of levosimendan administration on peripheral perfusion in the prodromic phases of sepsis and compare them with the variations in microcirculation perfusion occurring with conventional dobutamine therapy. Sixteen patients with sepsis were enrolled, eight of whom were treated with norepinephrine and levosimendan and the other eight with norepinephrine and dobutamine. We observed a trend of reduction in the hematic lactate concentration and an increase in peripheral perfusion in the patients treated with levosimendan. The latter also occurred in the dobutamine group, although to a lower degree. Hematic lactate was significantly reduced in the levosimendan group, probably because of the enhanced aerobic metabolism, due to both the action on mitochondrial KATP channels and the better oxygen delivery to cells. The lactate values varied from T0 (2.28 \u00b1 0.25 mmol\/L) to T2 (1.45 \u00b1 0.31 mmol\/L) in the levosimendan group vs. from T0 (2.79 \u00b1 0.91 mmol\/L) to T2 (2.92 \u00b1 0.76 mmol\/) L in the dobutamine group. Hence, levosimendan may be indicated in septic patients with impaired microcirculation and tissue oxygenation and, consequently, high lactate levels. Further studies are needed to draw a profile of levosimendan as a possible treatment to restore microcirculation in septic patients.<\/jats:p>","DOI":"10.3390\/life15060871","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T06:25:04Z","timestamp":1748499904000},"page":"871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effects of Levosimendan on Microcirculation and Peripheral Perfusion in Septic Shock: A Pilot Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Veronica","family":"Gagliardi","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, University of Padova, 35122 Padova, Italy"},{"name":"AIRAS, 36045 Lonigo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Ceccherelli","sequence":"additional","affiliation":[{"name":"AIRAS, 36045 Lonigo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5465-3646","authenticated-orcid":false,"given":"Antonello","family":"Lovato","sequence":"additional","affiliation":[{"name":"AIRAS, 36045 Lonigo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, University of Padova, 35122 Padova, Italy"},{"name":"AIRAS, 36045 Lonigo, Italy"},{"name":"Department of Anesthesiology and Intensive Care, Ospedale Santa Maria della Misericordia, 45100 Rovigo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1097\/00000658-199208000-00002","article-title":"Multiple organ failure. Pathophysiology and potential future therapy","volume":"216","author":"Deitch","year":"1992","journal-title":"Ann. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1056\/NEJMra1208623","article-title":"Severe sepsis and septic shock","volume":"369","author":"Angus","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1063","DOI":"10.1097\/CCM.0000000000005337","article-title":"Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021","volume":"49","author":"Evans","year":"2021","journal-title":"Crit Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1097\/00003246-199207000-00016","article-title":"Effect of septic serum on vascular smooth muscle: In vitro studies using rat aortic rings","volume":"20","author":"Hollenberg","year":"1992","journal-title":"Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0883-9441(86)80113-7","article-title":"Cardiovascular determinants of the hemodynamic response to acute endotoxemia in the dog","volume":"1","author":"Pinsky","year":"1986","journal-title":"J. Crit. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1186\/cc3753","article-title":"The microcirculation is the motor of sepsis","volume":"9","author":"Ince","year":"2005","journal-title":"Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1186\/cc3748","article-title":"Microvascular dysfunction as a cause of organ dysfunction in severe sepsis","volume":"9","author":"Vincent","year":"2005","journal-title":"Crit. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1097\/ACO.0000000000000957","article-title":"Septic shock: A microcirculation disease","volume":"34","author":"Ricottilli","year":"2021","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1152\/jappl.1996.81.2.885","article-title":"Heterogeneity of oxygen delivery impairs oxygen extraction by peripheral tissues: Theory","volume":"81","author":"Walley","year":"1996","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/cc3751","article-title":"The microcirculation as a functional system","volume":"9","author":"Ellis","year":"2005","journal-title":"Crit. Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1164\/rccm.200109-016OC","article-title":"Microvascular blood flow is altered in patients with sepsis","volume":"166","author":"Creteur","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/10739680590896072","article-title":"Potassium channels in the peripheral microcirculation","volume":"12","author":"Jackson","year":"2005","journal-title":"Microcirculation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"796","DOI":"10.21037\/atm.2020.04.43","article-title":"Inodilators in septic shock: Should these be used?","volume":"8","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1097\/00003246-200111000-00022","article-title":"Effects of levosimendan, a novel inotropic calcium-sensitizing drug, in experimental septic shock","volume":"29","author":"Oldner","year":"2001","journal-title":"Crit. Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/cc13842","article-title":"Ventriculoarterial decoupling in human septic shock","volume":"18","author":"Guarracino","year":"2014","journal-title":"Crit. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.biochi.2014.03.006","article-title":"Effects of levosimendan on mitochondrial function in patients with septic shock: A randomized trial","volume":"102","author":"Torraco","year":"2014","journal-title":"Biochimie"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.jcrc.2015.05.017","article-title":"Levosimendan reduces mortality in patients with severe sepsis and septic shock: A meta-analysis of randomized trials","volume":"30","author":"Zangrillo","year":"2015","journal-title":"J. Crit. Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jcrc.2016.08.010","article-title":"The effect of vasoactive drugs on mortality in patients with severe sepsis and septic shock. A network meta-analysis of randomized trials","volume":"37","author":"Belletti","year":"2017","journal-title":"J. Crit. Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jclinane.2017.03.011","article-title":"Levosimendan does not provide mortality benefit over dobutamine in adult patients with septic shock: A meta-analysis of randomized controlled trials","volume":"39","author":"Bhattacharjee","year":"2017","journal-title":"J. Clin. Anesth."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"R232","DOI":"10.1186\/cc9387","article-title":"Levosimendan for resuscitating the microcirculation in patients with septic shock: A randomized controlled study","volume":"14","author":"Morelli","year":"2010","journal-title":"Crit. Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1007\/s00134-005-2619-z","article-title":"Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression","volume":"31","author":"Morelli","year":"2005","journal-title":"Intensive Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1056\/NEJMoa1609409","article-title":"Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis","volume":"375","author":"Gordon","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1177\/0310057X1204000304","article-title":"The PiCCO monitor: A review","volume":"40","author":"Litton","year":"2012","journal-title":"Anaesth. Intensive Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1177\/1358836X9000100202","article-title":"Vasomotion and flowmotion: Physiological mechanisms and clinical evidence","volume":"vmr-1","author":"Intaglietta","year":"1990","journal-title":"Vasc. Med. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.mvr.2006.10.006","article-title":"Skin microcirculatory effect of exogenous calcitonin gene-related peptide (CGRP) evaluated by laser Doppler flowmetry coupled with iontophoresis in healthy subjects","volume":"73","author":"Rossi","year":"2007","journal-title":"Microvasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1097\/SHK.0000000000000851","article-title":"Effects of Levosimendan on Cellular Metabolic Alterations in Patients With Septic Shock: A Randomized Controlled Pilot Study","volume":"48","author":"Hajjej","year":"2017","journal-title":"Shock"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Onody, P., Stangl, R., Fulop, A., Rosero, O., Garbaisz, D., Turoczi, Z., Lotz, G., Rakonczay, Z., Balla, Z., and Hegedus, V. (2013). Levosimendan: A cardiovascular drug to prevent liver ischemia-reperfusion injury?. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073758"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1097\/SHK.0000000000001239","article-title":"Manipulating the Microcirculation in Sepsis\u2014The Impact of Vasoactive Medications on Microcirculatory Blood Flow: A Systematic Review","volume":"52","author":"Potter","year":"2019","journal-title":"Shock"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/6\/871\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:42:10Z","timestamp":1760031730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/6\/871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,28]]},"references-count":28,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["life15060871"],"URL":"https:\/\/doi.org\/10.3390\/life15060871","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2025,5,28]]}}}