Understanding Hyperlactatemia in Sepsis: Are We There Yet?
Ontology highlight
ABSTRACT:
SUBMITTER: Nalos M
PROVIDER: S-EPMC6794111 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
Understanding Hyperlactatemia in Sepsis: Are We There Yet?
Nalos Marek M Robergs Robert R
American journal of respiratory and critical care medicine 20191001 8
Similar Datasets
Project description: Not available
| S-EPMC6794110 | biostudies-literature
Project description: Not available
| S-EPMC6727157 | biostudies-literature
Project description:BackgroundSetting lactate kinetics at >30% might improve the clinical outcomes of patients with sepsis-associated hyperlactatemia. The aim of this study was to explore the outcome benefits of stepwise lactate kinetics vs central venous oxygen saturation (ScvO2)-oriented hemodynamic therapy at 6 h as the protocol goal during early resuscitation.MethodsThe relevant parameters and adverse events after different targets in 360 randomly assigned patients with sepsis-associated hyperlactatemia were recorded and compared.ResultsHeart rate (HR) at 48 h in the ScvO2 group was higher than in the lactate kinetics group (105 ± 19 bpm vs 99 ± 20 bpm, P = 0.040). The liquid balance at 4 h, 12 h, and 24 h in the lactate kinetics group was larger than in the ScvO2 group (1535 (1271-1778) ml vs 826 (631-1219) ml, P < 0.001; 1688 (1173-1923) ml vs 1277 (962 - 1588) ml, P <0.001; and 1510 (904-2087) ml vs 1236 (740-1808) ml, P = 0.005), respectively. Mortality was higher in the ScvO2 group (27.9% vs 18.3%, P = 0.033), but there was no significant difference between the two groups in the length of stay in the ICU or mechanical ventilation. In terms of new onset organ dysfunction, there was a significant difference between the two groups in total bilirubin at 48 h and 72 h. Based on the 60-day survival curves, there was significantly more mortality in the ScvO2 group than in the lactate kinetics group (X 2 = 4.133, P = 0.042). In addition, fewer adverse events occurred in the lactate kinetics group.ConclusionsStepwise lactate kinetics-oriented hemodynamic therapy can reduce mortality in patients with sepsis-associated hyperlactatemia compared with ScvO2-oriented therapy.Trial registrationNational Institutes of Health Clinical Trials Registry, NCT02566460 . Registered on 26 September 2015.
| S-EPMC5312433 | biostudies-literature
Project description:AbstractThe 2016 Surviving Sepsis Campaign guidelines suggest guiding resuscitation to normalize lactate levels in patients with sepsis-associated hyperlactatemia as a marker of tissue hypoperfusion. This study evaluated the prognostic value of lactate levels and lactate clearance for 30-day mortality in patients with sepsis and septic shock diagnosed in the emergency department.We performed a retrospective cohort study of sepsis patients with initial lactate levels of ≥2 mmol/L. All patients met the Sepsis-3 definitions. The prognostic value of 6-hour lactate levels, 6-hour lactate clearance, 6-hour lactate metrics (≥2 mmol/L), and lactate clearance metrics (<10%, <20%, and <30%) was evaluated. We compared the sensitivity and specificity between metrics.Of the 363 sepsis and septic shock patients, 148 died (30-day mortality: 40.8%). Nonsurvivors had significantly higher 6-hour lactate levels and lower 6-hour lactate clearance than those of survivors. Six-hour lactate levels and 6-hour lactate clearance were associated with 30-day mortality after adjusting for potential confounders (odds ratio, 1.191 [95% confidence interval (CI), 1.097-1.294] and 0.989 [0.983-0.995], respectively). Six-hour lactate levels had better prognostic value than 6-hour lactate clearance (area under the curve, 0.720 [95% CI, 0.670-0.765] vs 0.656 [0.605-0.705]; P = .02). Six-hour lactate levels of ≥3.5 mmol/L and 6-hour lactate clearance of <24.4% were the optimal cut-off value in predicting the 30-day mortality. The prognostic value of 6-hour lactate metrics and 6-hour lactate clearance metrics did not differ. Six-hour lactate levels (≥2 mmol/L) had the highest sensitivity (89.2%).Six-hour lactate levels proved to be more accurate in predicting 30-day mortality than 6-hour lactate clearance and initial lactate levels.
| S-EPMC7899836 | biostudies-literature
Project description:IntroductionAcute circulatory dysfunction in patients with sepsis can evolve rapidly into a progressive stage associated with high mortality. Early recognition and adequate resuscitation could improve outcome. However, since the spectrum of clinical presentation is quite variable, signs of hypoperfusion are frequently unrecognized in patients just admitted to the emergency department (ED). Hyperlactatemia is considered a key parameter to disclose tissue hypoxia but it is not universally available and getting timely results can be challenging in low resource settings. In addition, non-hypoxic sources can be involved in hyperlactatemia, and a misinterpretation could lead to over-resuscitation in an unknown number of cases. Capillary refill time (CRT) is a marker of peripheral perfusion that worsens during circulatory failure. An abnormal CRT in septic shock patients after ICU-based resuscitation has been associated with poor outcome. The aim of this study was to determine the prevalence of abnormal CRT in patients with sepsis-related hyperlactatemia in the early phase after ED admission, and its relationship with outcome.MethodsWe performed a prospective observational study. Septic patients with hyperlactemia at ED admission subjected to an initial fluid resuscitation (FR) were included. CRT and other parameters were assessed before and after FR. CRT-normal or CRT-abnormal subgroups were defined according to the status of CRT following initial FR, and major outcomes were registered.ResultsNinety-five hyperlactatemic septic patients were included. Thirty-one percent had abnormal CRT at ED arrival. After FR, 87 patients exhibited normal CRT, and 8 an abnormal one. Patients with abnormal CRT had an increased risk of adverse outcomes (88% vs. 20% p<0.001; RR 4.4 [2.7-7.4]), and hospital mortality (63% vs. 9% p<0.001; RR 6.7 [2.9-16]) as compared to those with normal CRT after FR. Specifically, CRT-normal patients required less frequently mechanical ventilation, renal replacement therapy, and ICU admission, and exhibited a lower hospital mortality.ConclusionsHyperlactatemic sepsis patients with abnormal CRT after initial fluid resuscitation exhibit higher mortality and worse clinical outcomes than patients with normal CRT.
| S-EPMC5703524 | biostudies-literature
Project description:Objective: The clinical interpretation of lactate ? 2.00 mmol/L in emergency department (ED) patients is not well-characterized. This study aims to determine the optimal cutoff value for lactate within the reference range that predicts in-hospital mortality among ED patients. Methods: This was a retrospective study of adult patients presenting to a tertiary ED with an initial serum lactate level of <2.00 mmol/L. The primary outcome was in-hospital mortality. Youden's index was utilized to determine the optimal threshold that predicts mortality. Patients above the threshold were labeled as having relative hyperlactatemia. Results: During the study period, 1,638 patients were included. The mean age was 66.9 ± 18.6 years, 47.1% of the population were female, and the most prevalent comorbidity was hypertension (56.7%). The mean lactate level at presentation was 1.5 ± 0.3 mmol/L. In-hospital mortality was 3.8% in the overall population, and 16.2% were admitted to the ICU. A lactate level of 1.33 mmol/L was found to be the optimal cutoff that best discriminates between survivors and non-survivors. Relative hyperlactatemia was an independent predictor of in-hospital mortality (OR 1.78 C1.18-4.03; p = 0.02). Finally, relative hyperlactatemia was associated with increased mortality in patients without hypertension (4.7 vs. 1.1%; p = 0.008), as well as patients without diabetes or COPD. Conclusion: The optimal cutoff of initial serum lactate that discriminates between survivors and non-survivors in the ED is 1.33 mmol/L. Relative hyperlactatemia is associated with increased mortality in emergency department patients, and this interaction seems to be more important in healthy patients.
| S-EPMC7536275 | biostudies-literature
Project description:To examine the association of statin use with clinical outcomes and circulating biomarkers in community-acquired pneumonia and sepsis.Multicenter inception cohort study.Emergency departments of 28 U.S. hospitals.A total of 1895 subjects hospitalized with community-acquired pneumonia.None.Our approach consisted of two different comparison cohorts, each reflecting methods used in prior publications in this area. We first compared subjects with prior statin use (prior use cohort), defined as a history of statin use in the week before admission, with those with no prior use. We then compared prior statin users whose statins were continued inhospital (continued use cohort) with those with either no prior use or no inhospital use. We adjusted for patient characteristics, including demographics, comorbid conditions, and illness severity, and accounted for healthy user effect and indication bias using propensity analysis. We determined risk of severe sepsis and 90-day mortality. We measured markers inflammation (tumor necrosis factor, interleukin-6, interleukin-10), coagulation (antithrombin, factor IX, plasminogen activator inhibitor, d-dimer, thrombin antithrombin complex), and lymphocyte cell surface protein expression during the first week of hospitalization. There were no differences in severe sepsis risk between statin users and nonusers for prior (30.8% vs. 30.7%, p = .98) or continued statin use (30.2% vs. 30.8%, p = .85) in univariate analyses and after adjusting for patient characteristics and propensity for statin use. Ninety-day mortality was similar in prior statin users (9.2% vs. 12.0%, p = .11) and lower in continued statin users (7.9% vs. 12.1%, p = .02). After adjusting for patient characteristics and propensity for statin use, there was no mortality benefit for prior (odds ratio, 0.90 [0.63-1.29]; p = .57) or continued statin use (odds ratio, 0.73 [0.47-1.13]; p = .15). Only antithrombin activity over time was higher in statin subjects, yet the magnitude of the difference was modest. There were no differences in other coagulation, inflammatory, or lymphocyte cell surface markers.We found no evidence of a protective effect for statin use on clinical outcomes and only modest differences in circulating biomarkers in community-acquired pneumonia, perhaps as a result of healthy user effects and indication bias.
| S-EPMC3139804 | biostudies-other
Project description:Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed.
| S-EPMC3962548 | biostudies-literature
Project description:BackgroundThe benefits of early antibiotics for sepsis have recently been questioned. Evidence for this mainly comes from observational studies. The only randomized trial on this subject, the Prehospital Antibiotics Against Sepsis (PHANTASi) trial, did not find significant mortality benefits from early antibiotics. That subgroups of patients benefit from this practice is still plausible, given the heterogeneous nature of sepsis.Research questionDo subgroups of sepsis patients experience 28-day mortality benefits from early administration of antibiotics in a prehospital setting? And what key traits drive these benefits?Study design and methodsWe used machine learning to conduct exploratory partitioning cluster analysis to identify possible subgroups of sepsis patients who may benefit from early antibiotics. We further tested the influence of several traits within these subgroups, using a logistic regression model.ResultsWe found a significant interaction between age and benefits of early antibiotics (P = .03). When we adjusted for this interaction and several other confounders, there was a significant benefit of early antibiotic treatment (OR, 0.07; 95% CI, 0.01-0.79; P = .03).InterpretationAn interaction between age and benefits of early antibiotics for sepsis has not been reported before. When validated, it can have major implications for clinical practice. This new insight into benefits of early antibiotic treatment for younger sepsis patients may enable more effective care.
| S-EPMC8546240 | biostudies-literature
Project description:An estimated 14.1 million patients survive sepsis each year. Many survivors experience poor long-term outcomes, including new or worsened neuropsychological impairment; physical disability; and vulnerability to further health deterioration, including recurrent infection, cardiovascular events, and acute renal failure. However, clinical trials and guidelines have focused on shorter-term survival, so there are few data on promoting longer-term recovery. To address this unmet need, the International Sepsis Forum convened a colloquium in February 2018 titled "Understanding and Enhancing Sepsis Survivorship." The goals were to identify gaps and limitations of current research and shorter- and longer-term priorities for understanding and enhancing sepsis survivorship. Twenty-six experts from eight countries participated. The top short-term priorities identified by nominal group technique culminating in formal voting were to better leverage existing databases for research, develop and disseminate educational resources on postsepsis morbidity, and partner with sepsis survivors to define and achieve research priorities. The top longer-term priorities were to study mechanisms of long-term morbidity through large cohort studies with deep phenotyping, build a harmonized global sepsis registry to facilitate enrollment in cohorts and trials, and complete detailed longitudinal follow-up to characterize the diversity of recovery experiences. This perspective reviews colloquium discussions, the identified priorities, and current initiatives to address them.
| S-EPMC6794113 | biostudies-literature