A community-based exercise intervention transitions metabolically abnormal obese adults to a metabolically healthy obese phenotype.

BACKGROUND: Lower habitual physical activity and poor cardiorespiratory fitness are common features of the metabolically abnormal obese (MAO) phenotype that contribute to increased cardiovascular disease risk. The aims of the present study were to determine 1) whether community-based exercise training transitions MAO adults to metabolically healthy, and 2) whether the odds of transition to metabolically healthy were larger for obese individuals who performed higher volumes of exercise and/or experienced greater increases in fitness. METHODS AND RESULTS: Metabolic syndrome components were measured in 332 adults (190 women, 142 men) before and after a supervised 14-week community-based exercise program designed to reduce cardiometabolic risk factors. Obese (body mass index ≥30 kg · m(2)) adults with two to four metabolic syndrome components were classified as MAO, whereas those with no or one component were classified as metabolically healthy but obese (MHO). After community exercise, 27/68 (40%) MAO individuals (P<0.05) transitioned to metabolically healthy, increasing the total number of MHO persons by 73% (from 37 to 64). Compared with the lowest quartiles of relative energy expenditure and change in fitness, participants in the highest quartiles were 11.6 (95% confidence interval: 2.1-65.4; P<0.05) and 7.5 (95% confidence interval: 1.5-37.5; P<0.05) times more likely to transition from MAO to MHO, respectively. CONCLUSION: Community-based exercise transitions MAO adults to metabolically healthy. MAO adults who engaged in higher volumes of exercise and experienced the greatest increase in fitness were significantly more likely to become metabolically healthy. Community exercise may be an effective model for primary prevention of cardiovascular disease.

Low and "supranormal" central venous oxygen saturation and markers of tissue hypoxia in cardiac surgery patients: a prospective observational study.

PURPOSE: To characterize incidence of low, normal and "supranormal" central venous oxygen saturation (ScvO(2)) and the relation to markers of tissue hypoxia, course and outcome in cardiac surgery patients. METHODS: Prospective, observational study in a university multidisciplinary 50-bed intensive care unit including 205 consecutive patients undergoing elective cardiac surgery. Data were split into training and test data sets and subjected to 50 replications of fivefold cross-validation to estimate lower and upper bounds of ScvO(2) indicative of impaired tissue oxygenation. RESULTS: Both low (≤ 60.8%) and supranormal (≥ 77.4%) ScvO(2) were associated with an unfavorable course, while the logistic EuroSCORE for risk adjustment was comparable between groups. Incidences of abnormal ScvO(2) were 13.2% low and 30.7% supranormal. Patients with low ScvO(2) and an uneventful course initially presented with normal lactate levels, whereas patients with supranormal ScvO(2) displayed consistently higher serum lactate levels. High ScvO(2) values were associated with the use of ß-mimetics and signs of systemic inflammation. Mortality rates were comparable for patient populations presenting either low (14.8%) or supranormal ScvO(2) (7.9%) and higher than normals (0%, p < 0.001). Lactate was comparably increased in patients that ultimately died, irrespective whether they had low or supranormal ScvO(2) values. In contrast, neither low nor supranormal ScvO(2) was associated with altered gastric pCO(2.) CONCLUSIONS: High ScvO(2) is an under-recognized warning sign for impaired tissue oxygenation in the peri-operative period. Including values ≥ 77.4% as 'normal' impaired performance of ScvO(2) monitoring to predict a complicated perioperative course.

Open randomized phase II trial of an extracorporeal endotoxin adsorber in suspected Gram-negative sepsis.

OBJECTIVE: An initial phase II trial to investigate the safety and therapeutic effect of the endotoxin adsorber system EN 500 in septic patients suffering from presumed Gram-negative infection. DESIGN: Open, controlled, prospective, randomized, multiple-center, parallel-group clinical trial. SETTING: Intensive care units of 31 university-affiliated and community hospitals in Europe. PATIENTS: One hundred forty-five patients with a clinical diagnosis of severe sepsis or septic shock due to suspected Gram-negative infection. INTERVENTIONS: Patients were randomized to receive either standard therapy alone for sepsis (n = 76) or standard therapy plus extracorporeal endotoxin adsorption (n = 67) daily for the first 4 days following study entry. MEASUREMENTS AND MAIN RESULTS: The primary end point was the proportion of responders (defined as a decrease in Acute Physiology and Chronic Health Evaluation II score by > or =4 points from study entry to day 4). Secondary outcomes were the Sequential Organ Failure Assessment score and its components, length of intensive care unit stay, survival rate, and safety of the adsorber treatment. Patient characteristics at entry were well balanced between the two treatment groups, except for a higher Sequential Organ Failure Assessment score in the adsorber group. On all-subjects-treated analysis, 65% of the adsorber group were responders vs. 57% for the standard (p =.389). A planned interim analysis restricted further enrollment to patients with peritonitis, in whom a slightly higher proportion of responders was observed with the adsorber treatment (69%) vs. standard treatment (54%, p =.159). There were no differences in survival, but adsorption treatment in peritonitis patients was associated with trends toward a reduction in length of intensive care unit stay and a more rapid decline in plasma endotoxin concentrations. There was a significantly greater reduction in platelet count with the adsorber; however, this did not require extra treatment. CONCLUSIONS: The endotoxin adsorber system did not result in a significantly improved primary end point in patients with presumed Gram-negative sepsis. In patients with peritonitis, the adsorber treatment likewise did not result in significantly improved Acute Physiology and Chronic Health Evaluation II scores. There were no clinically important side effects. These results provide encouragement for further study of adsorber treatment in patients with high likelihood of Gram-negative sepsis (e.g., peritonitis).

Continuous central venous and pulmonary artery oxygen saturation monitoring in the critically ill.

OBJECTIVE: To compare the course of continuously measured mixed and central venous O(2) saturations in high-risk patients and to evaluate the impact of various factors that might interfere with reflection spectrophotometry. DESIGN AND SETTING: Prospective, descriptive study in the interdisciplinary ICU of a university hospital. PATIENTS: 32 critically ill patients with triple-lumen central vein catheters, including 29 patients requiring pulmonary artery catheterization. INTERVENTIONS: The accuracy of fiberoptic measurements was assessed by comparison to reference co-oximeter results at regular intervals. We examined the effect on measurement accuracy of physiological variables including hematocrit, hemoglobin, pH, temperature, and the administration of various solutions via central venous catheter. Continuous parallel measurements of SvO(2) and ScvO(2) were performed in patients with each type of catheters over a total observation time of 1097 h. RESULTS: ScvO(2) values were more accurate and stable than in vitro oximeter measurements ( r=0.96 from 150 samples, mean difference 0.15%, average drift 0.10%/day) and was not significantly affected by synchronous infusion therapy or by changes in hematocrit, hemoglobin, pH, or temperature. ScvO(2) values closely paralleled SvO(2), whether measured in vitro ( r=0.88 from 150 samples) or in vivo ( r=0.81 from 395,128 samples) but averaged about 7+/-4 saturation percentage higher. ScvO(2) changed in parallel in 90% of the 1,498 instances in which SvO(2) changed more than 5% (over an average of 43 min). CONCLUSIONS: Continuous fiberoptic measurement of central vein O(2) saturation has potential to be a reliable and convenient tool which could rapidly warn of acute change in the oxygen supply/demand ratio of critically ill patients.

High-dose vasopressin is not superior to norepinephrine in septic shock.

OBJECTIVE: We examined the effects of arginine vasopressin, when substituted for norepinephrine as a vasopressor in septic shock, on global and hepatosplanchnic hemodynamic and oxygen transport variables. DESIGN: Experimental study. SETTING: Intensive care unit. SUBJECTS: Twelve septic shock patients. INTERVENTIONS: Norepinephrine was replaced by vasopressin in a dose sufficient to keep mean arterial blood pressure constant. Blood flow, oxygen delivery, and oxygen consumption of the hepatosplanchnic region (calculated by a hepatic venous catheter technique using the Fick principle during continuous infusion of indocyanine green), global hemodynamics (by thermodilution), and gastric regional PCO2 gap (by air tonometry) were calculated during infusion of norepinephrine (mean, 0.56 microg.kg-1.min-1; range, 0.18-1.1 microg.kg-1.min-1) and again 2 hrs after replacement by vasopressin (mean, 0.47 IU/min; range, 0.06-1.8 IU/min). MEASUREMENTS AND MAIN RESULTS: Cardiac index decreased significantly from 3.8 +/- 1.3 to 3.0 +/- 1.1 L.min-1.m-2, heart rate decreased from 96 +/- 14 to 80 +/- 16 min-1 (p <.01), and global oxygen uptake decreased from 248 +/- 67 to 218 +/- 75 mL/min (p <.05). Absolute splanchnic blood flow tended to increase, although not significantly, whereas fractional splanchnic blood flow increased from 10.8 +/- 7.6 to 25.9 +/- 16.6% of cardiac output (p <.05). Gastric regional PCO2 gap increased from 17.5 +/- 26.6 to 36.5 +/- 26.6 mm Hg (p <.01). CONCLUSION: Vasopressin, in doses sufficient to replace the vasopressor norepinephrine, had mixed effects in septic shock patients. Hepatosplanchnic blood flow was preserved during substantial reduction in cardiac output. An increased gastric PCO2 gap suggests that the gut blood flow could have been redistributed to the disadvantage of the mucosa. Based on these limited data, it does not appear beneficial to directly replace norepinephrine with vasopressin in septic shock.