摘要:

ObjectiveTo determine whether administration of recombinant adenovirus vectors encoding the interleukin (IL)-10 protein (AxCAmIL-10) decreases the mortality of septic mice.DesignProspective, randomized, controlled study.SettingUniversity research laboratory.SubjectsAdult male C57B/6 mice.InterventionsUntreated mice and those injected intraperitoneally with 1 × 109pfu of AxCAmIL-10 were used as control 1 and 2, respectively. Double-capsules withoutEscherichia coliwere intraperitoneally embedded in another group (control 3). Mice embedded with capsules containingE. coliwere divided into the following groups: simultaneous administration of 0.5 mL of saline (group 1), and administration of AxCAmIL-10 3 hrs before embedding (group 2) or 1 hr after embedding (group 3). Histopathologic changes together with expression concentrations of IL-10 and tumor necrosis factor (TNF) in various organs and plasma were examined 18 hrs after each treatment. Observation periods were 5–8 days. Survival rates were compared between these groups.Measurements and Main ResultsThe plasma IL-10 concentrations were increased in control 2, group 2, and group 3 but not in control 1, control 3, or group 1, indicating successful adenovirus gene transfer. Plasma TNF values were significantly reduced in groups 2 and 3 as compared with group 1, with no significant differences in endotoxin concentrations. Survival rates were significantly better in groups 2 and 3 than in group 1 (p< .05).ConclusionThese findings suggested that IL-10 has a favorable effect on survival of septic mice via inhibition of TNF production or endotoxin stimulation.

ISSN:0090-3493    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveAlthough substantial myocardial cell injury has been reported after high-energy electrical defibrillation, only minimal injury with transient functional defects seems to develop at energy levels not exceeding those required to reverse ventricular fibrillation. Because multiple electrical shocks are often delivered in clinical settings during attempts to reverse ventricular fibrillation, we investigated the effects of repetitive shocks on postresuscitation myocardial dysfunction by using an isolated rat heart model of ventricular fibrillation.DesignProspective and randomized.SettingCardiopulmonary resuscitation research laboratory.SubjectsTwenty-seven Sprague-Dawley rats.InterventionsHearts were harvested and perfused at a constant flow of 10 mL/min by using a modified Krebs-Henseleit solution equilibrated with 95% oxygen and 5% CO2. Ventricular fibrillation (VF) was induced by a 0.05-mA current delivered to the right ventricular endocardium and the perfusate flow was stopped. After 10 mins, the perfusate flow was resumed at 20% of baseline flow and maintained for 15 additional minutes before returning to baseline flow after 25 mins of VF (VF25 mins). Twenty-seven hearts were randomized to receive from VF22 minsto VF25 minseither 0 epicardial shocks, 6 epicardial shocks, or 12 epicardial shocks.Measurements and Main ResultsIsovolumic indices of left ventricular function were obtained by using a latex balloon advanced through the mitral valve into the ventricular cavity. After defibrillation, indices of contractile function rapidly returned to baseline without differences among groups. The isovolumic end-diastolic pressure, however, remained elevated throughout the postresuscitation interval. A left shift of the diastolic pressure-volume curves without changes in their slope was observed at 10 mins after resuscitation with partial return to baseline by 30 mins postresuscitation. The shifts were significantly greater in hearts that received 12 shocks.ConclusionsThese findings indicate that repetitive low-energy electrical shocks do not accentuate postischemic systolic dysfunction in the isolated fibrillating rat heart but adversely affect postischemic diastolic dysfunction by reducing the unstressed left ventricular end-diastolic volume.

ISSN:0090-3493    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo test the effect of a continuous infusion of the nitric oxide (NO) synthase (S) inhibitor aminoethyl-isothiourea (AE-ITU) on survival time, hemodynamics, and oxygen transport in a porcine model of live group A streptococcal (GAS) sepsis. Furthermore, to examine the role of endothelin-1, histamine, and reactive oxygen species (ROS) in streptococcal shock.DesignProspective, randomized trial.SettingLaboratory at a university hospital.SubjectsTwenty-eight pigs with an average weight of 25 kg.InterventionsSixteen animals received a continuous infusion of liveStreptococcus pyogenes1.3 × 1010colony forming units/hr: eight received fluids only, and the other eight received an intravenous infusion of AE-ITU 10 mg/kg/hr starting 30 mins before the GAS challenge. Six control pigs received AE-ITU 10 mg/kg/hr iv for 5 hrs. Another six animals received half the dose of GAS over 5 hrs.Measurements and Main ResultsGAS infusion caused a rapid increase in pulmonary, hepatic, and systemic vascular resistance, followed by hypotension with a 90% lethality at 4 hrs. Treatment with AE-ITU increased 4-hr survival in septic animals from 1/8 to 8/8 and 5-hr survival from 0/8 to 5/8, prevented hypotension, and increased urine output. AE-ITU attenuated the decrease in cardiac output, liver blood flow, and oxygen delivery, and hepatic arterial blood flow as a fraction of cardiac output increased (allp< .05). Plasma nitrate/nitrite levels decreased in all animals. Inducible NOS and endothelial constitutive NOS activities in liver, gut, and lung were not increased during sepsis, nor were they decreased after AE-ITU. Plasma levels of endothelin-1 and methylhistamine increased in all septic animals and were not modified by AE-ITU. AE-ITU prevented the increase in monocyte ROS production caused by GAS. In control animals, AE-ITU caused an increase in mean arterial pressure, liver blood flow, and oxygen delivery.ConclusionsIn this model of porcine GAS-induced septic shock, which was not associated with enhanced NO production, infusion of the NOS inhibitor AE-ITU prolonged survival, prevented hypotension, and improved cardiac contractility, organ perfusion, and tissue oxygenation. These beneficial effects of AE-ITU might be a result of the combined effect of ROS scavenging and modulation of local NO production, thus improving the balance of vasodilator and vasoconstrictor forces and reducing oxidative stress.

ISSN:0090-3493    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo analyze the single effect and the interaction of prone position and inhaled nitric oxide (iNO) on lung function and hemodynamic variables.Design2 × 2 factorial trial.SettingDepartment of intensive care medicine at a university hospital.PatientsFourteen patients on volume-controlled mechanical ventilation for acute respiratory distress syndrome (ARDS).InterventionFour experimental conditions, each one characterized by the patient’s position (supine or prone) with iNO or without iNO.Measurements and ResultsHemodynamic and gas exchange data were collected for each experimental condition. Pao2was increased both by positioning (p< .01) and iNO (p< .01); iNO caused also a reduction in venous admixture (p< .01), pulmonary artery pressure (p< .01), and pulmonary vascular resistance index (p< .05). We could not demonstrate any significant interaction between the two treatments. The average effect of prone positioning was the same both with and without iNO, whereas the average effect of iNO was the same in both the prone and the supine position.ConclusionIn the studied acute respiratory distress syndrome patients the average effects of iNO and positioning on oxygenation were additive and no interaction could be shown. A strategy including both treatments could warrant the best improvement in oxygenation, and should take into account the individual response to each treatment and the possible combination of the two.

ISSN:0090-3493    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundEndotoxin (lipopolysaccharide [LPS]) has been associated with sepsis and the high mortality rate seen in septic shock. The administration of a small amount of LPS to healthy subjects produces a mild syndrome qualitatively similar to that seen in clinical sepsis. We used this model to test the efficacy of an endotoxin antagonist, E5531, in blocking this LPS-induced syndrome.MethodsIn a placebo-controlled, double-blind study, we randomly assigned 32 healthy volunteers to four sequential groups (100, 250, 500, or 1000 &mgr;g of E5531). Each group of eight subjects (six assigned to E5531, two assigned to placebo) received a 30-min intravenous infusion of study drug. LPS (4 ng/kg) was administered to all subjects as an intravenous bolus in the contralateral arm at the midpoint of the infusion. Symptoms, signs, laboratory values, and hemodynamics (by echocardiogram) were evaluated at prospectively defined times.ResultsIn subjects receiving placebo, LPS caused headache, nausea, chills, and myalgias. E5531 led to a dose-dependent decrease in these symptoms that was statistically significant (p< .05) except for myalgias. The signs of endotoxemia (fever, tachycardia, and hypotension) were consistently inhibited at the three higher doses (250, 500, and 1000 &mgr;g,p< .05). Tumor necrosis factor-&agr; and interleukin-6 blood levels were both lower in those who received E5531 (p< .0001). The C-reactive protein level and white blood cell count response were decreased at all doses (p< .0001). The hyperdynamic cardiovascular state (high cardiac index and low systemic vascular resistance) associated with endotoxin challenge was significantly inhibited at the higher doses of E5531.ConclusionsE5531 blocks the symptoms and signs and cytokine, white blood cell count, C-reactive protein, and cardiovascular response seen in experimental endotoxemia. This agent is a potent inhibitor of endotoxin challenge in humans and may be of benefit in the prevention or treatment of sepsis and septic shock.

ISSN:0090-3493    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo test the hypothesis that replacing 70:30 nitrogen:oxygen (Air-O2) with 70:30 helium:oxygen (He-O2) can decrease dynamic hyperinflation (“intrinsic” positive end-expiratory pressure) in mechanically ventilated patients with chronic obstructive pulmonary disease (COPD), and to document the consequences of such an effect on arterial blood gases and hemodynamics.DesignProspective, interventional study.SettingMedical intensive care unit, university tertiary care center.PatientsTwenty-three intubated, sedated, paralyzed, and mechanically ventilated patients with COPD enrolled within 36 hrs after intubation.InterventionsMeasurements were taken at the following time points, all with the same ventilator settings: a) baseline; b) after 45 mins with He-O2; c) 45 mins after return to Air-O2. The results were then compared to those obtained in a test lung model using the same ventilator settings.Main Results (mean ± sd):Trapped lung volume and intrinsic positive end-expiratory pressure decreased during He-O2ventilation (215 ± 125 mL vs. 99 ± 15 mL and 9 ± 2.5 cm H2O vs. 5 ± 2.7 cm H2O, respectively;p< .05). Likewise, peak and mean airway pressures declined with He-O2(30 ± 5 cm H2O vs. 25 ± 6 cm H2O and 8 ± 2 cm H2O vs. 7 ± 2 cm H2O, respectively;p< .05). These parameters all rose to their baseline values on return to Air-O2(p< .05 vs. values during He-O2). These results were in accordance with those obtained in the test lung model. There was no modification of arterial blood gases, heart rate, or mean systemic arterial blood pressure. In 12/23 patients, a pulmonary artery catheter was in place, allowing hemodynamic measurements and venous admixture calculations. Switching to He-O2and back to Air-O2had no effect on pulmonary artery pressures, right and left ventricular filling pressures, cardiac output, pulmonary and systemic vascular resistance, or venous admixture.ConclusionIn mechanically ventilated COPD patients with intrinsic positive end-expiratory pressure, the use of He-O2can markedly reduce trapped lung volume, intrinsic positive end-expiratory pressure, and peak and mean airway pressures. No effect was noted on hemodynamics or arterial blood gases. He-O2might prove beneficial in this setting to reduce the risk of barotrauma, as well as to improve hemodynamics and gas exchange in patients with very high levels of intrinsic positive end-expiratory pressure.

ISSN:0090-3493    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo measure the effects of increasing mean arterial pressure (MAP) on systemic oxygen metabolism and regional tissue perfusion in septic shock.DesignProspective study.SettingMedical and surgical intensive care units of a tertiary care teaching hospital.PatientsTen patients with the diagnosis of septic shock who required pressor agents to maintain a MAP ≥ 60 mm Hg after fluid resuscitation to a pulmonary artery occlusion pressure (PAOP) ≥ 12 mm Hg.InterventionsNorepinephrine was titrated to MAPs of 65, 75, and 85 mm Hg in 10 patients with septic shock.Measurements and Main ResultsAt 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/m2to 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 Pco2and gastric intramucosal Pco2was 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.ConclusionsIncreasing 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.

ISSN:0090-3493    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesTo evaluate the relationship of the genotype distribution of the tumor necrosis factor (TNF)-&agr; polymorphism with regard to the plasma TNF-&agr; concentration and the development of septic shock as well as mortality of infected patients in a surgical intensive care unit (SICU).DesignA total of 112 postoperative critically ill infected patients were prospectively enrolled.SettingSICU of a tertiary university-affiliated medical center.PatientsPatients who were consecutively admitted to the SICU because of surgical infection with sepsis.InterventionBlood sampling.Measurements and Main ResultsBlood sample was obtained 24 hrs after intensive care unit (ICU) admission or within 2 hrs after the onset of septic shock to determine the plasma TNF-&agr; level and to analyze the genotype of the biallelic polymorphism of the TNF-&agr;.ResultsThe allele frequency of the TNF2 in our infected ICU patients was 12%. Forty-two (37.5%) patients admitted fulfilled the criteria of septic shock during their ICU stay. Patients carrying the TNF2 allele were not more likely to develop septic shock, nor did they have a higher mortality rate. In the patients with septic shock, those carrying the TNF2 allele had a significantly higher mortality rate than those with the homozygous TNF1 genotype (92% vs. 62%,p< .05). In those who developed septic shock, the TNF2 allele was significantly associated with higher TNF levels.ConclusionIn patients admitted to SICU with surgical infection, the frequency of TNF2 allele was higher than in the general population. SICU patients with TNF2 allele did not show a higher incidence of developing septic shock, nor was there a higher baseline TNF-&agr; level after infection. However, once septic shock had developed, the mortality rate was higher in those patients carrying the TNF2 allele.

ISSN:0090-3493    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo assess how data obtained by invasive diagnostic techniques may affect management and outcome of patients with suspected ventilator-associated pneumonia (VAP), in comparison with noninvasive qualitative techniques.DesignProspective study.SettingAn 18-bed medical and surgical intensive care unit.PatientsA total of 91 patients suspected of having VAP were randomized into two groups. In group A (n = 45), quantitative cultures obtained by either bronchoscopic or nonbronchoscopic techniques were performed, whereas in group B (n = 43), patients were treated based on clinical judgment and nonquantitative tracheal aspirates cultures. Three patients were excluded because of the absence of follow-up.ResultsIn patients with positive cultures, therapeutic changes were made in 20 patients. In four patients (three from group A and one from group B,p= NS), initial empirical antibiotic treatment was modified because the isolated microorganisms were not susceptible (all of them had late-onset pneumonia). The isolated organisms responsible for antibiotic modifications were methicillin-resistantStaphylococcus aureus(three patients) andPseudomonas aeruginosa(one patient). In three patients, the antimicrobial therapy was considered inappropriate because the isolated microorganisms were multiresistant and treated with only one effective antibiotic. In 13 patients (ten from group A and three from group B,p< .05), treatment was changed to select a narrower spectrum antibiotic. No therapeutic modifications were made in patients with negative cultures based on the results of quantitative cultures.The overall mortality was 22.2% in group A and 20.9% in group B. There were no differences in intensive care unit stay or days of mechanical ventilation (23.67 ± 3.15 vs. 22.42 ± 3.01 and 19.99 ± 2.88 vs. 19.24 ± 3.04, respectively).ConclusionsIn our study population, the routine use of quantitative invasive diagnostic tools is not justified in the setting of ventilated patients clinically suspected of having nosocomial pneumonia.

ISSN:0090-3493    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo determine hospital mortality, weaning from mechanical ventilation, long-term survival, and functional health status in patients receiving ≥7 days of mechanical ventilation after cardiac surgery.DesignRetrospective chart review and prospective patient interviews.SettingA university-affiliated, tertiary care medical center.PatientsA total of 124 patients that received ≥7 days of mechanical ventilation after cardiac surgery.InterventionsNone.Main Outcome MeasuresHospital and long-term death, liberation from mechanical ventilation, and functional health status.Measurements and Main ResultsA total of 19 (15%) patients died in hospital. Of the 105 survivors, 104 (99%) were completely weaned from mechanical ventilation. Patients who died in the hospital were more likely to have had a preoperative stroke or to have a new postoperative stroke, more likely to have postoperative renal failure, and less likely to have chronic obstructive pulmonary disease. Kaplan-Meier survival was 59% at 5 yrs and expected median survival was 6.2 yrs. Patients who died anytime after discharge were more likely to have preoperative renal dysfunction or stroke, took longer to be weaned from mechanical ventilation and to be discharged, and were more likely to have postoperative complications such as stroke or renal dysfunction. Also, they were more likely to be too debilitated to walk or eat. By multivariate analysis, admitting creatinine, aortic valve surgery, number of ventilator days, and discharged on tube feedings remained significant predictors of mortality. A total of 40 of 53 survivors were interviewed. Participants were similar to nonparticipants (p> .10 for all characteristics). A few (16%) had limitations of their activities of daily living (eating, dressing, bathing), and most had limitations of moderate activity (60%) and vigorous activity (94%). Only 36% could climb stairs or walk uphill without limitations, 54% could walk a block, and 41% had no limitations in house or job work. Half the participants had no body pain; 38% had moderate and 4% severe pain. Most (59%) described their general health as good to excellent. Only 10% said it was poor.ConclusionPatients’ chances of being liberated from mechanical ventilation are excellent. Their long-term survival and health status are good.

ISSN:0090-3493    

出版商:OVID    

年代:2000

数据来源: OVID