Biomedical subjects

Fuhong Su

Publications and source records attributed to Fuhong Su.

8 recordsLinked to original sources

PubMed2006

Euglycemic hyperinsulinemia in severe sepsis and septic shock.

BACKGROUND: Recent studies have suggested that strict glucose control with intensive insulin therapy in critically ill patients may result in better outcomes. Whether this is also true in septic shock has not been determined. In addition, whether it is the insulin administration per se or the glucose control that contributes to the beneficial effects is unclear. We raised the hypothesis that euglycemic hyperinsulinemia (EH) might improve the outcome from septic shock due to peritonitis. MATERIALS AND METHODS: Fourteen anesthetized, mechanically ventilated, and hemodynamically monitored sheep received 1.5 g/kg body weight i.p. feces to induce sepsis. Ringer's lactate and 6% hydroxyethyl starch solutions were infused throughout the experiment to prevent hypovolemia. Two hours after feces injection, the animals were randomized to either an EH group (n = 7) receiving insulin 0.25 U/ kg/h, 20% glucose (to maintain blood glucose at 40-90 mg/dl), and potassium (to maintain the potassium level at 4.0- 5.5 mmol/l) or a control group (n = 7) with no intervention. All animals were studied until their spontaneous death or for 30 h. RESULTS: The EH group received a greater volume of 20% glucose, but blood glucose and potassium concentrations were similar in the two groups. No significant differences were found in hemodynamic variables. The circulating interleukin-6 levels increased in both groups after feces injection, but tended to be lower in the EH group (p < 0.05). The survival times were similar in the two groups (median 20.0 h in the EH group vs. 17.0 h in the control group; p = 0.73). CONCLUSIONS: In this clinically relevant sheep septic shock model, EH decreased blood interleukin-6 concentrations but did not change hemodynamics or improve the outcome.

Animals↗

PubMed2006

Blood warming during hemofiltration can improve hemodynamics and outcome in ovine septic shock.

BACKGROUND: This study was designed to evaluate the effects of blood warming during hemofiltration on global and regional hemodynamics, plasma lactate, and 24-h survival during septic shock. METHODS: Twenty anesthetized and mechanically ventilated sheep underwent induction of peritonitis and, 4 h later, were treated by hemofiltration with (n = 10) or without (n = 10) blood warming. RESULTS: In the group without blood warming, body temperature decreased after starting hemofiltration and remained below baseline. In the other animals, body temperature stabilized at baseline level during hemofiltration and increased to a maximum of 40.8 degrees C thereafter. The group without warming experienced a decrease in blood pressure (from 90 mmHg to 38 mmHg) and cardiac output (from 4.0 l/min to 2.3 l/min). Metabolic acidosis and the increase in lactate were less marked when temperature was maintained. None of the animals without warming but all of the animals with warming survived to 16 h. CONCLUSIONS: Differences in temperature during hemofiltration resulted in striking differences in hemodynamics, metabolic acidosis, and survival rate in this clinically relevant experimental model of septic shock.

Acidosis, Lactic↗

PubMed2006

Elevated serum levels of S-100beta protein and neuron-specific enolase are associated with brain injury in patients with severe sepsis and septic shock.

OBJECTIVE: We investigated whether serum levels of neuron-specific enolase (NSE) and S-100beta protein could be used to evaluate cerebral injury and to predict outcome in severe sepsis and severe septic shock. DESIGN: Prospective study. SETTING: University hospital. PATIENTS AND MEASUREMENTS: In 170 consecutively enrolled patients with severe sepsis and septic shock, serum S-100beta and NSE were measured daily during four consecutive days after intensive care unit admission. Admission Glasgow Coma Scale before sedation and daily Sequential Organ Failure Assessment scores were recorded in all patients. Acute encephalopathy was defined as either a state of agitation, confusion, irritability, and convulsions (type A) or characterized by somnolence, stupor, and coma (type B) and persistently observed during 72 hrs after withdrawing sedation. When clinically indicated, contrast computed tomography or magnetic resonance imaging were performed to evaluate brain injury. MAIN RESULTS: S-100beta and NSE increased in, respectively, 72 (42%) and 90 (53%) patients. High biomarker levels were associated with the maximum Sequential Organ Failure Assessment scores (p = .001), and the highest values were found in patients who died early, within 4 days of inclusion (p = .005). Low consciousness encephalopathy type B was more frequently observed in patients with elevated S-100beta (p = .004). S-100beta levels of >or=4 microg/L were associated with severe brain ischemia or hemorrhage, and values of <2 microg/L were found in patients with diffuse cerebral embolic infarction lesions. High S-100beta levels were associated with higher intensive care unit mortality (p = .04) and represented the strongest independent predictor of intensive care unit survival, whereas NSE and the Glasgow Coma Scale failed to predict fatal outcome. CONCLUSIONS: S-100beta and NSE are frequently increased and associated with brain injury in patients with severe sepsis and septic shock. S-100beta levels more closely reflected severe encephalopathy and type of brain lesions than NSE and the Glasgow Coma Scale.

Adolescent↗

PubMed2006

Beneficial effects of alkaline phosphatase in septic shock.

OBJECTIVE: Alkaline phosphatase may decrease the harmful effects of lipopolysaccharide by detoxifying lipid A. The aim of this study was to investigate whether administration of alkaline phosphatase is beneficial in a clinically relevant septic shock model. DESIGN: Interventional laboratory study. SETTING: University hospital animal research laboratory. SUBJECTS: Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (27.6 +/- 3.9 kg). INTERVENTIONS: Each animal received 1.5 g/kg body weight of feces intraperitoneally to induce sepsis. Ringer's lactate and a 6% hydroxyethyl starch solution were infused throughout the experiment to prevent hypovolemia. Two hours after feces injection, animals were randomized to alkaline phosphatase (60 units/kg intravenous bolus followed by a continuous infusion of 20 units/kg/hr for a total of 15 hrs) or no alkaline phosphatase (control group). MEASUREMENTS AND MAIN RESULTS: All animals were studied until their spontaneous death or for a maximum of 30 hrs. Plasma alkaline phosphatase concentrations decreased in the control group but increased in the treatment group following alkaline phosphatase administration. In the treatment group, the Pao2/Fio2 ratio was higher (p < .05), blood interleukin-6 concentrations were lower (p < .05), and the survival time was longer (median time 23.8 vs. 17 .0 hrs, p < 0.05) than in the control group. There were no significant differences in systemic hemodynamics or diuresis. CONCLUSIONS: In this clinically relevant septic shock model, alkaline phosphatase administration improved gas exchange, decreased interleukin-6 concentrations, and prolonged survival time.

Alkaline Phosphatase↗

PubMed2006

Effects of dexamethasone on macrophage migration inhibitory factor production in sepsis.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a major role in the pathogenesis of sepsis. Some studies have indicated that glucocorticoids increase MIF production in physiological conditions. The goal of this study was to determine whether glucocorticoid treatment also upregulates MIF production in sepsis. Male NMRI mice (6-10 weeks old) underwent laparotomy, proximal ligation of the cecum, and double perforation with a 19-gauge needle (cecal ligation and puncture). Mice were randomly treated with saline (control) or dexamethasone at doses of 0.1, 1, or 10 mg/kg ip. At 6 or 18 h postoperatively, 10 mice per group were euthanized; and blood, peritoneal fluid, liver, lung, kidney, and heart tissue samples were retrieved. MIF, IL-6, TNF-alpha, and IL-10 were measured by enzyme-linked immunosorbent assay. Sepsis induced by cecal ligation and puncture produced a marked increase in MIF and cytokine levels in plasma and peritoneal fluid. Treatment with dexamethasone 10 mg/kg decreased MIF levels in plasma after 18 h, but there was no effect of dexamethasone on MIF production locally in the peritoneal cavity or in the liver, lungs, heart, or kidneys. We conclude that glucocorticoid treatment does not upregulate MIF production in sepsis.

Animals↗

PubMed2005

Rapid alterations in transferrin sialylation during sepsis.

The inflammatory process is associated with alterations in iron metabolism. Transferrin, an acute-phase N-glycosylated glycoprotein, plays an important role in iron transport. Human serum transferrin contains two biantennary glycans, each consisting of 0 to 4 molecules of sialic acid (SA); its SA content is heterogeneous with high concentration of tetrasialotransferrin (4SA) and low amounts of disialo-, trisialo-, penta-, and hexasialotransferrin. The hepatic uptake of iron is greater for desialylated transferrin isoforms (disialotransferrin) than for the other forms. We hypothesized that serum levels of carbohydrate-deficient transferrin (CDT, disialotransferrin) may increase rapidly in septic patients. Blood samples were obtained from critically ill patients with (n = 15) and without (n = 14) documented sepsis and compared with healthy volunteers. The different forms of transferrin were studied by capillary zone electrophoresis; SA concentrations were measured by enzymatic colorimetric assay. There was a significant increase in the proportion of CDT in septic compared with nonseptic patients and volunteers (18.3% [1.3-30.5] vs. 0.7% [0.5-0.9]; P < 0.01 and 0.9% [0.5-1.1]; P < 0.05). Conversely, tri- and tetrasialotransferrin levels were lower in septic patients. Total and free SA concentrations were significantly higher in septic patients than in healthy volunteers. In a sheep model of septic shock secondary to peritonitis, serum free SA was already increased after 15 h. Sepsis is associated with decreased SA content on circulating transferrin and with an increase in blood free SA concentrations. In view of these rapid modifications and the long half-life of transferrin, the most likely explanation is degradation of transferrin by neuraminidase. Further studies including measurement of blood neuraminidase concentration and activity are needed to understand the process and exact role of SA decrease in septic patients.

Acute Disease↗

PubMed2005

Fever control in septic shock: beneficial or harmful?

The beneficial effects of interventions to control fever in sepsis are controversial. We investigated whether the use of acetaminophen and external cooling is beneficial to control fever in septic shock. We studied 24 fasted, anesthetized, invasively monitored, mechanically ventilated female sheep (27.0 +/- 4.6 kg) that received 0.5 g/kg body weight of feces into the abdominal cavity to induce sepsis. Ringer's lactate (RL) was titrated to maintain pulmonary artery occlusion pressure (PAOP) at baseline levels throughout the experimental period. During the 2 h after the surgical operation, animals were placed in the hypothermia group if their temperature fell below 36.0 degrees C; the other animals were randomized to three groups: high fever (T > 39.0 degrees C), mild fever (37.5 degrees C < T < 38.5 degrees C), and normothermia (36.0 degrees C < T < 37.0 degrees C). The administration of 25 mg/kg acetaminophen every 4 to 6 h combined with external cooling (ice pad) was used to control core temperature in these three groups. The PaO2/FiO2 ratio was higher and blood lactate concentration was lower in the high fever than in the other groups (P < 0.01 and 0.05, respectively). Survival time was longer in the high fever group (25.2 +/- 3.0 h) than in the mild fever (17.7 +/- 3.5 h), normothermia (16.0 +/- 1.9 h), and hypothermia (18.5 +/- 2.5 h) groups (P < 0.05 for all). Plasma heat shock protein (HSP) 70 levels were higher in the two fever groups than in the other groups (P < 0.05). In this clinically relevant septic shock model, the febrile response thus resulted in better respiratory function, lower blood lactate concentration, and prolonged survival time. Antipyretic interventions including acetaminophen and external cooling were associated with lower circulating HSP70 levels. These data challenge the temperature control practices often used routinely in acutely ill patients.

Acetaminophen↗

PubMed2004

Use of low tidal volume in septic shock may decrease severity of subsequent acute lung injury.

Recent studies have indicated that protective lung strategies may improve outcomes in acute lung injury. We hypothesized that the use of a lower tidal volume early during septic shock may protect against the subsequent development of acute lung injury. Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (26.4 +/- 4.5 kg) underwent cecal ligation and perforation to induce sepsis. Sheep were then randomized to ventilation with low (6 mL/kg) or high (12 mL/kg) tidal volumes. A positive end-expiratory pressure of 10 cm H(2)O was applied in each case. Ringer's lactate was titrated to maintain pulmonary artery occlusion pressure at baseline levels. No vasoactive agents or antibiotics were used. Survival time was longer in the low- than in the high-tidal-volume group (21.8 +/- 2.4 vs. 17.6 +/- 4.1 h, respectively, P < 0.05). The times to develop hypotension and anuria were longer in the low-tidal-volume group (18.1 +/- 3.1 vs. 12.0 +/- 2.8 h, P < 0.05, and 17.6 +/- 1.6 vs. 14.1 +/- 3.8 h, P < 0.05). Although the Pao2/Fio2 tended to be lower in the low- than in the high-tidal-volume group (P = 0.06), postmortem examination showed a lower lung tissue wet/dry ratio in the low- than in the high-tidal-volume group (7.1 +/- 0.5 vs. 9.1 +/- 0.7, P < 0.05). A low-tidal-volume ventilation strategy applied early during septic shock may be beneficial in terms of reducing the amount of lung edema and prolonging survival time.

Animals↗