Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

Abstract

BackgroundLactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock.MethodsMeasurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED.ResultsTwo-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01).ConclusionsEarly lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock.

Predictors of Acute Kidney Injury in Septic Shock Patients

“…In a study of 300 persons with severe sepsis and evidence of hypoperfusion who were admitted to the emergency department, ScVO 2 did not prove a superior target than lactate clearance for goal-directed resuscitation and the mortality rate was not reduced by ScVO 2 to lactate clearance monitoring (43). Moreover, the mean levels of biomarkers of inflammation, coagulation and apoptosis, organ dysfunction scores, and mortality were significantly lower with higher lactate clearance in patients with sepsis (44). An important "hypothesis generating" finding was that transfusion of blood products in septic shock patients was independently associated with AKI.…”

The Involvement of Cholesterol in Sepsis and Tolerance to Lipopolysaccharide Highlighted by the Transcriptome Analysis of Zebrafish (Danio rerio)

“…Lactate concentration is a measure of tissue hypoxia and is sufficient for the diagnosis of septic shock. 37 Three apoptosis-related proteins were also up-modulated in 4-dpf fish: diablo, IAPbinding mitochondrial protein (DIABLO); DNA fragmentation factor, alpha polypeptide (DFFA); and caspase blike and one in 6-dpf fish: a protein with homology to pleckstrin (PLEKHF1) that was reported to be an important intermediate in the activation pathways of inflammatory reactions. 38 In the pathogenesis of sepsis, inflammation and coagulation play pivotal roles.…”

Peran Bersihan Laktat pada Kesintasan Pasien Sepsis Berat

“…10,11 Pada penelitian yang dilakukan oleh Nguyen, dkk. 12 , didapatkan bahwa kelompok pasien dengan bersihan laktat yang rendah secara bermakna membutuhkan penggunaan ventilator dan vasopresor yang lebih tinggi dibandingkan dengan kelompok lainnya. Pada penelitian tersebut didapatkan juga bahwa kelompok pasien dengan bersihan laktat yang lebih tinggi memperlihatkan penurunan penanda biologis proinflamasi, anti-inflamasi, dan koagulasi yang lebih besar.…”

“…Pada penelitian tersebut didapatkan juga bahwa kelompok pasien dengan bersihan laktat yang lebih tinggi memperlihatkan penurunan penanda biologis proinflamasi, anti-inflamasi, dan koagulasi yang lebih besar. 12 Serupa dengan penelitianpenelitian sebelumnya, angka mortalitas 28 dan 60 hari menurun seiring dengan semakin besar bersihan laktat yang dicapai. 12,13 Secara umum, kemampuan klinisi untuk memperkirakan terjadinya kematian di dalam penanganan pasien sepsis berat dengan menggunakan parameter klinis tervalidasi yang praktis memiliki beberapa manfaat.…”

“…12 Serupa dengan penelitianpenelitian sebelumnya, angka mortalitas 28 dan 60 hari menurun seiring dengan semakin besar bersihan laktat yang dicapai. 12,13 Secara umum, kemampuan klinisi untuk memperkirakan terjadinya kematian di dalam penanganan pasien sepsis berat dengan menggunakan parameter klinis tervalidasi yang praktis memiliki beberapa manfaat. Di antara manfaat tersebut yaitu manfaat dalam penentuan pengambilan keputusan oleh tenaga medis dan keluarga, menentukan bentuk pendekatan dan perawatan yang terbaik bagi pasien, serta antisipasi dan alokasi dari penggunaan alat bantu (obat vasopresor, ventilator, dan hemodialisas) atau sumber daya lainnya.…”