Quantitative Assessment of Blood Lactate in Shock: Measure of Hypoxia or Beneficial Energy Source.

Blood lactate concentration predicts mortality in critically ill patients and is clinically used in the diagnosis, grading of severity, and monitoring response to therapy of septic shock. This paper summarizes available quantitative data to provide the first comprehensive description and critique of the accepted concepts of the physiology of lactate in health and shock, with particular emphasis on the controversy of whether lactate release is simply a manifestation of tissue hypoxia versus a purposeful transfer ("shuttle") of lactate between tissues. Basic issues discussed include (1) effect of nonproductive lactate-pyruvate exchange that artifactually enhances flux measurements obtained with labeled lactate, (2) heterogeneous tissue oxygen partial pressure (Krogh model) and potential for unrecognized hypoxia that exists in all tissues, and (3) pathophysiology that distinguishes septic from other forms of shock. Our analysis suggests that due to exchange artifacts, the turnover rate of lactate and the lactate clearance are only about 60% of the values of 1.05 mmol/min/70 kg and 1.5 L/min/70 kg, respectively, determined from the standard tracer kinetics. Lactate turnover reflects lactate release primarily from muscle, gut, adipose, and erythrocytes and uptake by the liver and kidney, primarily for the purpose of energy production (TCA cycle) while the remainder is used for gluconeogenesis (Cori cycle). The well-studied physiology of exercise-induced hyperlactatemia demonstrates massive release from the contracting muscle accompanied by an increased lactate clearance that may occur in recovering nonexercising muscle as well as the liver. The very limited data on lactate kinetics in shock patients suggests that hyperlactatemia reflects both decreased clearance and increased production, possibly primarily in the gut. Our analysis of available data in health and shock suggests that the conventional concept of tissue hypoxia can account for most blood lactate findings and there is no need to implicate a purposeful production of lactate for export to other organs.

Combined Measurement of Soluble ST2 and Amino-Terminal Pro-B-Type Natriuretic Peptide Provides Early Assessment of Severity in Cardiogenic Shock Complicating Acute Coronary Syndrome.

OBJECTIVES: Mortality in cardiogenic shock complicating acute coronary syndrome is high, and objective risk stratification is needed for rational use of advanced therapies such as mechanical circulatory support. Traditionally, clinical variables have been used to judge risk in cardiogenic shock. The aim of this study was to assess the added value of serial measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide to clinical parameters for risk stratification in cardiogenic shock. DESIGN: CardShock (www.clinicaltrials.gov NCT01374867) is a prospective European multinational study of cardiogenic shock. The main study introduced CardShock risk score, which is calculated from seven clinical variables at baseline, and was associated with short-term mortality. SETTING: Nine tertiary care university hospitals. PATIENTS: Patients with cardiogenic shock caused by acute coronary syndrome (n=145). INTERVENTIONS: In this substudy, plasma samples from the study patients were analyzed at eight time points during the ICU or cardiac care unit stay. Additional prognostic value of the biomarkers was assessed with incremental discrimination improvement. MEASUREMENTS AND MAIN RESULTS: The combination of soluble ST2 and amino-terminal pro-B-type natriuretic peptide showed excellent discrimination for 30-day mortality (area under the curve, 0.77 at 12 hr up to 0.93 at 5-10 d after cardiogenic shock onset). At 12 hours, patients with both biomarkers elevated (soluble ST2, ≥ 500 ng/mL and amino-terminal pro-B-type natriuretic peptide, ≥ 4,500 ng/L) had higher 30-day mortality (79%) compared to those with one or neither biomarkers elevated (31% or 10%, respectively; p < 0.001). Combined measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide at 12 hours added value to CardShock risk score, correctly reclassifying 11% of patients. CONCLUSIONS: The combination of results for soluble ST2 and amino-terminal pro-B-type natriuretic peptide provides early risk assessment beyond clinical variables in patients with acute coronary syndrome-related cardiogenic shock and may help therapeutic decision making in these patients.

Noninvasive assessment of hemodynamic variables using near-infrared spectroscopy in patients experiencing cardiogenic shock and individuals undergoing venoarterial extracorporeal membrane oxygenation.

PURPOSE: The relationship between near-infrared spectroscopy cerebral oximetry (CrSO2), peripheral oximetry (PrSO2) and hemodynamic variables is not fully understood. METHODS: The relationship between CrSO2/PrSO2 and cardiac index (CI), systemic vascular resistance index (SVRI) and mean arterial pressure (MAP) in patients experiencing cardiogenic shock and those undergoing venoarterial extracorporeal membrane oxygenation (ECMO) was retrospectively analyzed; in patients on ECMO, total circulatory index (TCI) was calculated from the sum of CI and extracorporeal blood flow index. RESULTS: In patients experiencing cardiogenic shock (n=10), significant correlations between PrSO2 values and CI (Spearman r=0.81; P<.0001), SVRI (r=-0.45; P<.0001), and MAP (r=0.58; P<.0001) were found. Significant correlations between CrSO2 and CI (r=0.55; P<.0001) and SVRI (r=-0.47; P<.0001), but not MAP, were observed. Linear regression analysis revealed that CI could be calculated using the following equation: CI=PrSO2/24.0. In patients on VA ECMO (n=12), significant correlations were found between PrSO2 and TCI (r=0.68; P<.0001), SVRI (r=-0.47; P<.0001), and MAP (r=0.27; P=.025). Significant correlations were also found between CrSO2 and TCI (r=0.68; P<.0001) and SVRI (r=-0.51; P<.0001), but not MAP. CONCLUSIONS: Results of the present study suggest that CrSO2 and PrSO2 in particular can be used for noninvasive estimation and monitoring of global circulatory status in patients experiencing cardiogenic shock and individuals undergoing ECMO.

High lactate levels are predictors of major complications after cardiac surgery.

OBJECTIVE: Although hyperlactatemia after cardiac surgery is common, the implications of raised levels remain controversial. The aim of this study was to evaluate whether high lactate levels after cardiac surgery are predictors of major complications including mortality. PATIENTS AND METHODS: This was a substudy of TRACS (Transfusion Requirements After Cardiac Surgery), which was designed as a prospective, randomized, controlled trial evaluating the effects of a transfusion strategy on morbidity and mortality. RESULTS: Of the 502 patients enrolled, 52 (10%) had at least 1 major complication. Patients with complications were older, had a higher EuroSCORE, lower left ventricular ejection fraction, lower preoperative hemoglobin, a higher prevalence of renal disease, and received more blood transfusions than the group without complications. Lactate levels were higher in the group with complications at the end of surgery (3.6 mmol/L [2.8-5.1] vs 3.3 mmol/L [2.2-4.8]; P = .018), immediately after intensive care unit (ICU) admission (0 hour) (4.4 mmol/L [3.1-8.4] vs 4 mmol/L [2.6-6.4]; P = .048); 6 hours (4 mmol/L [2.7-5.8] vs 2.6 mmol/L [2-3.6], P < .001), and 12 hours after admission (2.3 mmol/L [1.8-3.2] vs 1.7 mmol/L [1.3-2]; P < .001). In a multivariate model, higher age (odds ratio [OR], 1.048, 95% confidence interval [CI], 1.011-1.086; P = .010), left ventricular ejection fraction (LVEF) lower than 40% (OR, 3.03; 95% CI, 1.200-7.510; P = .019 compared with LVEF of 40%-59%; OR, 3.571; 95% CI, 1.503-8.196; P = .004 compared with LVEF higher than 60%), higher EuroSCORE (OR, 1.138; 95% CI; 1.007-1.285; P = .038), red blood cell transfusion (OR, 1.230; 95% CI, 1.086-1.393; P = .001), and lactate levels 6 hours after ICU admission (OR, 3.28, 95% CI; 1.61-6.69; P = .001) are predictors of major complications. CONCLUSIONS: Hyperlactatemia 6 hours after ICU admission is an independent risk factor for worse outcomes in adult patients after cardiac surgery.

Early assessment of outcome in cardiogenic shock: relevance of plasma N-terminal pro-B-type natriuretic peptide and interleukin-6 levels.

OBJECTIVE: Plasma N-terminal pro-B-type natriuretic peptide (Nt-pro-BNP) levels are frequently elevated in critically ill patients and are associated with an increased mortality. In this study, we determined Nt-pro-BNP levels in patients with cardiogenic shock (CS) and evaluated its association with clinical and hemodynamic parameters and 30-day mortality. DESIGN: Retrospective study. SETTING: Two, eight-bed intensive care units at a university and a community hospital. PATIENTS: Retrospective study on stored plasma samples of 58 patients with CS, obtained at admission to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Massively elevated Nt-pro-BNP concentrations showed no significant association with duration of shock, total Sequential Organ Failure Assessment score, or invasive hemodynamic parameters at the time of blood sampling but a significant association with estimated glomerular filtration rate (p < 0.001), C-reactive protein (p = 0.03), age (p = 0.005), and body weight (p = 0.03). Both in univariate and multivariate survival analyses, Nt-pro-BNP levels above the median (>12,782 pg/mL) were significant predictors of 30-day mortality (p < 0.001) and showed a complementary role with interleukin (IL)-6 in predicting outcome. Patients with IL-6 >195 pg/mL and Nt-pro-BNP above the median value had the highest 30-day mortality (93.7%), whereas patients with lower IL-6 levels together with lower Nt-pro-BNP levels had significantly better survival (mortality rate 26.3%). Among patients who had acute myocardial infarction, those with Nt-pro-BNP concentrations above the median level showed a highly impaired clinical course even if coronary revascularization was successful (30-day mortality 90.9% vs. 29.4%, p = 0.001), whereas survival of patients with unsuccessful revascularization did not differ significantly with respect to the median of Nt-pro-BNP (30-day survival rate 81.8% vs. 75.0%, p = 0.71). CONCLUSION: The massive elevations of Nt-pro-BNP observed in the early phase of CS seem to be independent of ventricular performance. Nt-pro-BNP levels are nevertheless predictive of 30-day survival in patients with CS especially in those with successful revascularization and might be used in combination with IL-6 for estimation of outcome early on.

Blood transfusion requirements and independent predictors of increased transfusion requirements among adult patients on extracorporeal membrane oxygenation -- a single centre experience.

BACKGROUND/OBJECTIVES: More adults undergo extracorporeal membrane oxygenation (ECMO) now. They have high transfusion requirements. This study described transfusion requirements of adults during ECMO in a single institution, and determined factors associated with high transfusion requirements. MATERIALS/METHODS: Retrospective analysis was done on the amount of blood products received by adults during ECMO. Predictors of increased average daily transfusion requirements during ECMO and increased ECMO duration (which correlated positively with total transfusion requirements) were determined. RESULTS: Forty-one patients (median age 50 years) underwent 42 ECMO sessions for respiratory failure (16.7%), cardiogenic shock (76.2%) or massive pulmonary embolism (7.1%). They received 569 red blood cells, 852 platelets, 126 fresh-frozen plasma (FFP) and 220 cryoprecipitate in total during median ECMO duration of 5 (1-15) days. On multivariate analysis, average daily red blood cell transfusion increased with nadir haemoglobin (Hb) during ECMO (Hb(nadir)) of < 7.5 g/dl (P < 0.001). Average daily platelet transfusion increased with recent antiplatelet agents (P = 0.015) and maximum Hb decline of > 5.5 g/dl during ECMO (P = 0.011). Average daily platelet transfusion > 3 units was also associated with increased ECMO duration (P = 0.024). Average daily FFP transfusion was increased in patients with hypertension (P = 0.007) and Hb(nadir) < 7.5 g/dl (P = 0.050). Patients with sepsis (P = 0.009) or without surgery (P = 0.009) had increased ECMO duration, which correlated positively with total transfusion requirements during the entire ECMO session. ECMO improved mortality of patients with fulminant myocarditis, respiratory failure and massive pulmonary embolism. CONCLUSION: Adult ECMO patients with lower Hb(nadir) require more daily red blood cell and FFP. Hypertension increases daily FFP requirements. Recent antiplatelet agents, larger Hb decline and longer ECMO duration increase daily platelet requirements. Patients with sepsis or on ECMO for medical reasons have longer ECMO duration, which is associated with total transfusion requirements. Some of these factors may be identified early to optimize blood product support.