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      Clinical manifestations of disordered microcirculatory perfusion in severe sepsis

      review-article
      1 , , 2
      Critical Care
      BioMed Central
      Re-establishing organ function in severe sepsis: targeting the microcirculation
      2132005

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          Abstract

          Microcirculatory dysfunction plays a pivotal role in the development of the clinical manifestations of severe sepsis. Prior to the advent of new imaging technologies, clinicians had been limited in their ability to assess the microcirculation at the bedside. Clinical evidence of microcirculatory perfusion has historically been limited to physical examination findings or surrogates that could be derived from global parameters of oxygen transport. This review explores: (1) the clinical manifestations of severe sepsis that can be linked to microcirculatory dysfunction; (2) the relationship between conventional hemodynamic parameters and microcirculatory blood flow indices; (3) the incorporation of microcirculatory function into the definition of 'shock' in the sepsis syndrome; (4) the role of the microcirculation in oxygen transport; and (5) the potential impact of novel sepsis therapies on microcirculatory flow. Although the study of the microcirculation has long been the domain of basic science, newly developed imaging technologies, such as orthogonal polarization spectral imaging, have now given us the ability to directly visualize and analyze microcirculatory blood flow at the bedside, and see the microcirculatory response to therapeutic interventions. Disordered microcirculatory flow can now be associated with systemic inflammation, acute organ dysfunction, and increased mortality. Using new technologies to directly image microcirculatory blood flow will help define the role of microcirculatory dysfunction in oxygen transport and circulatory support in severe sepsis.

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          Most cited references28

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          Early lactate clearance is associated with improved outcome in severe sepsis and septic shock.

          Serial lactate concentrations can be used to examine disease severity in the intensive care unit. This study examines the clinical utility of the lactate clearance before intensive care unit admission (during the most proximal period of disease presentation) as an indicator of outcome in severe sepsis and septic shock. We hypothesize that a high lactate clearance in 6 hrs is associated with decreased mortality rate. Prospective observational study. An urban emergency department and intensive care unit over a 1-yr period. A convenience cohort of patients with severe sepsis or septic shock. Therapy was initiated in the emergency department and continued in the intensive care unit, including central venous and arterial catheterization, antibiotics, fluid resuscitation, mechanical ventilation, vasopressors, and inotropes when appropriate. Vital signs, laboratory values, and Acute Physiology and Chronic Health Evaluation (APACHE) II score were obtained at hour 0 (emergency department presentation), hour 6, and over the first 72 hrs of hospitalization. Therapy given in the emergency department and intensive care unit was recorded. Lactate clearance was defined as the percent decrease in lactate from emergency department presentation to hour 6. Logistic regression analysis was performed to determine independent variables associated with mortality. One hundred and eleven patients were enrolled with mean age 64.9 +/- 16.7 yrs, emergency department length of stay 6.3 +/- 3.2 hrs, and overall in-hospital mortality rate 42.3%. Baseline APACHE II score was 20.2 +/- 6.8 and lactate 6.9 +/- 4.6 mmol/L. Survivors compared with nonsurvivors had a lactate clearance of 38.1 +/- 34.6 vs. 12.0 +/- 51.6%, respectively (p =.005). Multivariate logistic regression analysis of statistically significant univariate variables showed lactate clearance to have a significant inverse relationship with mortality (p =.04). There was an approximately 11% decrease likelihood of mortality for each 10% increase in lactate clearance. Patients with a lactate clearance> or =10%, relative to patients with a lactate clearance <10%, had a greater decrease in APACHE II score over the 72-hr study period and a lower 60-day mortality rate (p =.007). Lactate clearance early in the hospital course may indicate a resolution of global tissue hypoxia and is associated with decreased mortality rate. Patients with higher lactate clearance after 6 hrs of emergency department intervention have improved outcome compared with those with lower lactate clearance.
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            Effects of perfusion pressure on tissue perfusion in septic shock.

            To measure the effects of increasing mean arterial pressure (MAP) on systemic oxygen metabolism and regional tissue perfusion in septic shock. Prospective study. Medical and surgical intensive care units of a tertiary care teaching hospital. Ten patients with the diagnosis of septic shock who required pressor agents to maintain a MAP > or = 60 mm Hg after fluid resuscitation to a pulmonary artery occlusion pressure (PAOP) > or = 12 mm Hg. Norepinephrine was titrated to MAPs of 65, 75, and 85 mm Hg in 10 patients with septic shock. At each level of MAP, hemodynamic parameters (heart rate, PAOP, cardiac index, left ventricular stroke work index, and systemic vascular resistance index), metabolic parameters (oxygen delivery, oxygen consumption, arterial lactate), and regional perfusion parameters (gastric mucosal Pco2, skin capillary blood flow and red blood cell velocity, urine output) were measured. Increasing the MAP from 65 to 85 mm Hg with norepinephrine resulted in increases in cardiac index from 4.7+/-0.5 L/min/m2 to 5.5+/-0.6 L/min/m2 (p < 0.03). Arterial lactate was 3.1+/-0.9 mEq/L at a MAP of 65 mm Hg and 3.0+/-0.9 mEq/L at 85 mm Hg (NS). The gradient between arterial P(CO2) and gastric intramucosal Pco2 was 13+/-3 mm Hg (1.7+/-0.4 kPa) at a MAP of 65 mm Hg and 16+/-3 at 85 mm Hg (2.1+/-0.4 kPa) (NS). Urine output at 65 mm Hg was 49+/-18 mL/hr and was 43+/-13 mL/hr at 85 mm Hg (NS). As the MAP was raised, there were no significant changes in skin capillary blood flow or red blood cell velocity. Increasing the MAP from 65 mm Hg to 85 mm Hg with norepinephrine does not significantly affect systemic oxygen metabolism, skin microcirculatory blood flow, urine output, or splanchnic perfusion.
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              Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock.

              Recent reports have shown that oxygen delivery (Do2) and oxygen uptake (Vo2) could be related to outcome of critically ill patients. In this study, we examined measurements of cardiac output, oxygen-derived variables, and blood lactate levels in 48 patients with documented septic shock. There were 27 survivors and 21 nonsurvivors from the shock episode. For all 174 observations, there was a significant linear relationship between Vo2 and Do2 (Vo2 = 79 + 0.17 x Do2, r = 0.64, p less than 0.001). There were no significant differences in Do2 between survivors and nonsurvivors at the onset of septic shock (mean +/- SD, 540 +/- 219 vs 484 +/- 222 ml/min.m2, NS) or in the final phase of septic shock (506 +/- 163 vs 443 +/- 187 ml/min.m2, NS). Also, no significant differences were found in Vo2 and oxygen extraction between survivors and nonsurvivors. However, survivors had significantly lower blood lactate levels both initially (5.1 +/- 2.7 vs 8.2 +/- 5.4 mmol/L, p less than 0.05) and in the final phase of septic shock (2.6 +/- 1.9 vs 7.7 +/- 5.6 mmol/L, p less than 0.001). Only the survivors had a significant decrease in blood lactate levels during the course of septic shock (p less than 0.001). We conclude that the oxygen-derived variables, Do2 and Vo2, cannot be used as prognostic indicators in human septic shock. In contrast, blood lactate levels are closely related to ultimate survival from septic shock. Furthermore, decreases in blood lactate levels during the course of septic shock could indicate a favorable outcome. Therefore, blood lactate levels can serve as a reliable clinical guide to therapy.
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                Author and article information

                Conference
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2005
                25 August 2005
                : 9
                : Suppl 4
                : S20-S26
                Affiliations
                [1 ]Section of Critical Care Medicine and the Department of Emergency Medicine, UMDNJ-Robert Wood Johnson Medical School at Camden, Cooper University Hospital, Camden, New Jersey, USA
                [2 ]Departments of Emergency Medicine and Surgery, Henry Ford Hospital, Detroit, Michigan, USA
                Article
                cc3744
                10.1186/cc3744
                3226160
                16168070
                31cf653a-c500-453d-bbe0-8bc761698811
                Copyright ©2005 BioMed Central Ltd
                Re-establishing organ function in severe sepsis: targeting the microcirculation
                Brussels, Belgium
                2132005
                History
                Categories
                Review

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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