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

BACKGROUND: Lactate 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. METHODS: Measurements 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. RESULTS: Two-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). CONCLUSIONS: Early 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.

Clinical utility of B-type natriuretic peptide in early severe sepsis and septic shock.

B-type natriuretic peptide (BNP) has diagnostic, therapeutic, and prognostic utility in critically ill patients. For severe sepsis and septic shock patients in particular, similar clinical utility from the most proximal aspects of hospital presentation to the intensive care unit has not been examined. BNP levels were measured at 0, 3, 6, 12, 24, 36, 48, 60, and 72 hours in 252 patients presenting to the emergency department with severe sepsis and septic shock. The clinicians were blinded to the BNP levels. Elevated BNP levels (>100 pg/mL) were seen in 42% and 69% of patients on presentation and at 24 hours, respectively. Elevated BNP ranges (>230 pg/mL) were significantly associated with myocardial dysfunction and severity of global tissue hypoxia. When adjusted for age, gender, history of heart failure, renal function, organ dysfunction, and mean arterial pressure, a BNP greater than 210 pg/mL at 24 hours was the most significant independent indicator of increased mortality: odds ratio 1.061 (1.026-1.097), P < .001, 95% confidence interval. Patients with severe sepsis and septic shock often have elevated BNP levels, which are significantly associated with organ and myocardial dysfunction, global tissue hypoxia, and mortality. Serial BNP levels may be a useful adjunct in the early detection, stratification, treatment, and prognostication of high-risk patients.

The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock.

BACKGROUND: Despite abundant experimental studies of biomarker patterns in early severe sepsis and septic shock, human data are few. Further, the impact of the severity of global tissue hypoxia resulting from resuscitative strategies on these early biomarker patterns remains unknown. METHODS: The temporal patterns of interleukin-1 receptor antagonist, intercellular adhesion molecule-1, tumor necrosis factor-alpha, caspase-3, and interleukin-8 were serially examined over the first 72 hrs of hospitalization after early hemodynamic optimization strategies of early goal-directed vs. standard therapy for severe sepsis and septic shock patients. The relationship of these biomarker patterns to each hemodynamic optimization strategy, severity of global tissue hypoxia (reflected by lactate and central venous oxygen saturation), organ dysfunction, and mortality were examined. RESULTS: Abnormal biomarker levels were present upon hospital presentation and modulated to distinct patterns within 3 hrs based on the hemodynamic optimization strategy. The temporal expression of these patterns over 72 hrs was significantly associated with the severity of global tissue hypoxia, organ dysfunction, and mortality. CONCLUSION: In early severe sepsis and septic shock, within the first 3 hrs of hospital presentation, distinct biomarker patterns emerge in response to hemodynamic optimization strategies. A significant association exists between temporal biomarker patterns in the first 72 hrs, severity of global tissue hypoxia, organ dysfunction, and mortality. These findings identify global tissue hypoxia as an important contributor to the early inflammatory response and support the role of hemodynamic optimization in supplementing other established therapies during this diagnostic and therapeutic "window of opportunity."

Effective lactate clearance is associated with improved outcome in post-cardiac arrest patients.

INTRODUCTION: Early, effective lactate clearance has been shown to be associated with improved mortality in patients with trauma, burns, and sepsis. We investigated whether early, high lactate clearance was associated with reduced mortality in post-cardiac arrest patients. METHODS: We performed a retrospective analysis of post-cardiac arrest patients in an urban emergency department. Inclusion criteria included pre-hospital cardiac arrest patients over the age of 18. Exclusion criteria were traumatic arrest, successful resuscitation prior to the arrival of emergency medical services, and cardiac arrest in the presence of pre-hospital providers. Primary endpoints consisted of survival to 24h and survival to hospital discharge. RESULTS: A total of 79 patients were analyzed with a mean age of 64+/-17 and mean APACHE II score of 37.7+/-5. Of the 79 patients, 27 (34%) died within 24h and 66 (84%) died during the hospital course. The mean initial lactate level for the overall group was 15+/-5.2mmol/dl with a mean lactate of 14.4+/-5.1mmol/dl in the survivors and 16+/-5.3mmol/dl in the non-survivors (p>0.05). Lactate clearance at both 6 and 12h was significantly higher for both 24-h and overall in-hospital survival (p<0.05). A multivariable analysis showed that high lactate clearance at 12h was predictive of 24-h survival (p<0.05). CONCLUSIONS: Early, effective lactate clearance is associated with decreased early and overall in-hospital mortality in post-cardiac arrest patients. These findings suggest that post-arrest tissue hypo-perfusion plays in an important role in early as well as overall mortality.