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Lactate Clearance in Septic Shock Is Not a Surrogate for Improved Microcirculatory Flow.

ABSTRACT: Failure to normalize lactate is associated with poor outcomes in septic shock. It has been suggested that persistently elevated lactate may result from regional ischemia due to disturbed and/or heterogenous microcirculatory blood flow.The goal of this study was to determine if lactate clearance (LC) may serve as a surrogate marker for changes in microcirculatory blood flow in patients with septic shock.This was a prospective observational study performed within a previously published clinical trial of l-carnitine for the treatment of vasopressor-dependent septic shock. Intravital video microscopy was performed at enrollment and 12 hours later, and microcirculatory flow index (MFI) was assessed. Associations between enrollment MFI, lactate, and Sequential Organ Failure Assessment (SOFA) score were determined, in addition to associations between ?MFI, LC, and ?SOFA. A preplanned subgroup analysis of only patients with an elevated initial lactate was performed.We enrolled a total of 31 patients, 23 with survival and sufficient quality videos both at enrollment and at 12 hours. ?MFI, LC, and ?SOFA were 0.1 (interquartile range [IQR] = 0 to 0.3), 18% (IQR = -10% to 46%), and -2 (IQR = -4 to 0). Both ?MFI and LC were associated with ?SOFA (? = -5.3, p = 0.01; and ? = -3.5, 0.047), but not with each other, even in the subgroup of patients with an initially elevated lactate.We observed no association between degree of LC and change in microcirculatory blood flow in patients with septic shock. These data suggest against the hypothesis that LC may be used as a surrogate marker of microcirculatory blood flow.

SUBMITTER: Puskarich MA

PROVIDER: S-EPMC5027836 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Lactate Clearance in Septic Shock Is Not a Surrogate for Improved Microcirculatory Flow.

Puskarich Michael A MA Shapiro Nathan I NI Massey Michael J MJ Kline Jeffrey A JA Jones Alan E AE

Academic emergency medicine : official journal of the Society for Academic Emergency Medicine 20160511 6

<h4>Background</h4>Failure to normalize lactate is associated with poor outcomes in septic shock. It has been suggested that persistently elevated lactate may result from regional ischemia due to disturbed and/or heterogenous microcirculatory blood flow.<h4>Objectives</h4>The goal of this study was to determine if lactate clearance (LC) may serve as a surrogate marker for changes in microcirculatory blood flow in patients with septic shock.<h4>Methods</h4>This was a prospective observational stu ...[more]

PMID: 26825368

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Project description:BackgroundRecent clinical studies have confirmed the strong prognostic value of persistent hyperlactatemia and delayed lactate clearance in septic shock. Several potential hypoxic and nonhypoxic mechanisms have been associated with persistent hyperlactatemia, but the relative contribution of these factors has not been specifically addressed in comprehensive clinical physiological studies. Our goal was to determine potential hemodynamic and perfusion-related parameters associated with 6-hour lactate clearance in a cohort of hyperdynamic, hyperlactatemic, septic shock patients.MethodsWe conducted an acute clinical physiological pilot study that included 15 hyperdynamic, septic shock patients undergoing aggressive early resuscitation. Several hemodynamic and perfusion-related parameters were measured immediately after preload optimization and 6 hours thereafter, with 6-hour lactate clearance as the main outcome criterion. Evaluated parameters included cardiac index, mixed venous oxygen saturation, capillary refill time and central-to-peripheral temperature difference, thenar tissue oxygen saturation (StO2) and its recovery slope after a vascular occlusion test, sublingual microcirculatory assessment, gastric tonometry (pCO2 gap), and plasma disappearance rate of indocyanine green (ICG-PDR). Statistical analysis included Wilcoxon and Mann-Whitney tests.ResultsFive patients presented a 6-hour lactate clearance <10%. Compared with 10 patients with a 6-hour lactate clearance ≥10%, they presented a worse hepatosplanchnic perfusion as represented by significantly more severe derangements of ICG-PDR (9.7 (8-19) vs. 19.6 (9-32)%/min, p < 0.05) and pCO2 gap (33 (9.1-62) vs. 7.7 (3-58) mmHg, p < 0.05) at 6 hours. No other systemic, hemodynamic, metabolic, peripheral, or microcirculatory parameters differentiated these subgroups. We also found a significant correlation between ICG-PDR and pCO2 gap (p = 0.02).ConclusionsImpaired 6-hour lactate clearance could be associated with hepatosplanchnic hypoperfusion in some hyperdynamic septic shock patients. Improvement of systemic, metabolic, and peripheral perfusion parameters does not rule out the persistence of hepatosplanchnic hypoperfusion in this setting. Severe microcirculatory abnormalities can be detected in hyperdynamic septic shock patients, but their role on lactate clearance is unclear. ICG-PDR may be a useful tool to evaluate hepatosplanchnic perfusion in septic shock patients with persistent hyperlactatemia.Trial registrationClinicalTrials.gov Identifier: NCT01271153.

Project description:Background: Some septic shock patients have persistent hyperlactacidemia despite a normal systemic hemodynamics after resuscitation. Central venous oxygen saturation (ScvO2), mean arterial pressure (MAP), and central venous pressure (CVP) cannot be target in subsequent hemodynamic treatments. Vasoplegia is considered to be one of the main causes of oxygen metabolism abnormalities in septic shock patients, and norepinephrine (NE) is the first-line vasopressor in septic shock treatment; its dosage represents the severity of vasoplegia. This study was performed to determine whether vasoplegia, as assessed by NE dosage, can indicate patients' lactate clearance after the completion of resuscitation. Methods: A retrospective study was performed, and 106 patients with septic shock in an intensive care unit were analyzed. Laboratory values and hemodynamic variables were obtained upon completion of resuscitation (H 0) and 6 h after (H 6). Lactate clearance was defined as the percent decrease in lactate from H 0 to H 6. Student's t-test, Mann-Whitney U-test, Chi-square or Fisher's exact tests, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were performed for statistical analysis. Results: Patients with a mean age of 63.7 ± 13.8 years, baseline APACHE II score of 21.0 ± 5.1, and SOFA score of 12.7 ± 2.7 were enrolled. The study found that after 6-h of resuscitation, lactate clearance (LC) was <10% in 33 patients (31.1%). Patients with 6-h LC <10% compared with 6-h LC ≥ 10% had a higher NE dose (μg·kg-1·min-1) (0.55 [0.36-0.84] vs. 0.25 [0.18-0.41], p < 0.001). Multivariate logistic regression analysis of statistically significant univariate variables showed that NE dose had a significant inverse relationship with 6-h LC < 10%. The cutoff for NE was ≥ 0.32 μg·kg-1·min-1 for predicting 6-h lactate clearance after resuscitation, with a sensitivity of 75.76% and a specificity of 70.00%. Septic shock patients with an NE dose ≥ 0.32 μg·kg-1·min-1, relative to patients with an NE dose < 0.32 μg·kg-1·min-1, had a greater 30-day mortality rate (69.8% vs. 26.4% p < 0.001). Conclusion: Some patients with septic shock had persistent oxygen metabolism disorders after hemodynamic resuscitation. NE dose may indicate vasoplegia and oxygen metabolism disorder. After resuscitation, septic shock patients with high-dose NE have lower lactate clearance and a greater 30-day mortality rate than those with low-dose NE.

Project description:BackgroundPersistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomized controlled trial to address the impact of a CRT-targeted (CRT-T) vs. a lactate-targeted (LAC-T) fluid resuscitation strategy on fluid balances within 24 h of septic shock diagnosis. In addition, we compared the effects of both strategies on organ dysfunction, regional and microcirculatory flow, and tissue hypoxia surrogates.ResultsForty-two fluid-responsive septic shock patients were randomized into CRT-T or LAC-T groups. Fluids were administered until target achievement during the 6 h intervention period, or until safety criteria were met. CRT-T was aimed at CRT normalization (≤ 3 s), whereas in LAC-T the goal was lactate normalization (≤ 2 mmol/L) or a 20% decrease every 2 h. Multimodal perfusion monitoring included sublingual microcirculatory assessment; plasma-disappearance rate of indocyanine green; muscle oxygen saturation; central venous-arterial pCO2 gradient/ arterial-venous O2 content difference ratio; and lactate/pyruvate ratio. There was no difference between CRT-T vs. LAC-T in 6 h-fluid boluses (875 [375-2625] vs. 1500 [1000-2000], p = 0.3), or balances (982[249-2833] vs. 15,800 [740-6587, p = 0.2]). CRT-T was associated with a higher achievement of the predefined perfusion target (62 vs. 24, p = 0.03). No significant differences in perfusion-related variables or hypoxia surrogates were observed.ConclusionsCRT-targeted fluid resuscitation was not superior to a lactate-targeted one on fluid administration or balances. However, it was associated with comparable effects on regional and microcirculatory flow parameters and hypoxia surrogates, and a faster achievement of the predefined resuscitation target. Our data suggest that stopping fluids in patients with CRT ≤ 3 s appears as safe in terms of tissue perfusion. Clinical Trials: ClinicalTrials.gov Identifier: NCT03762005 (Retrospectively registered on December 3rd 2018).

Project description:BackgroundCirculatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCDNG, RBCvNG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target.MethodsSublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock.Results54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCvNG. Heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), capillary refill time (p < 0.01), and Mottling score (p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCDNG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCDNG similar to baseline FCD found in patients without shock.ConclusionCritically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.

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Lactate Clearance in Septic Shock Is Not a Surrogate for Improved Microcirculatory Flow.

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Lactate Clearance in Septic Shock Is Not a Surrogate for Improved Microcirculatory Flow.

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