摘要:

ObjectiveProlonged mechanical ventilation is a common complication after coronary artery bypass graft surgery. Tumor necrosis factor &agr; is an important proinflammatory mediator in the post–coronary artery bypass graft inflammatory cascade. We attempted to study the effect of polymorphisms at the −308 site in the promoter region of the tumor necrosis factor gene (TNF−308) and the +250 site within the lymphotoxin-&agr; gene (LT&agr;+250) on the risk of prolonged mechanical ventilation after coronary artery bypass grafting.DesignProspective observational study.SettingTertiary care center.PatientsA total of 400 patients undergoing coronary artery bypass grafting were enrolled.MeasurementsThe primary end point was time to extubate. Secondary end points were the percentages of patients extubated at 8, 24, and 48 hrs; the length of intensive care unit and hospital stay; the need for a rehabilitation facility; and 30-day mortality. Precollected blood was used for gene analysis. Genotyping was performed by polymerase chain reaction and restriction enzyme digestion.Main ResultsPatients with an AA genotype at the LT&agr;+250 site and those without the LT&agr;+250G/−308TNFG haplotype had a shorter duration of mechanical ventilation (11.5 vs. 27.8 hrs and 11.2 vs. 29.4 hrs;p= .039 and .01, respectively). The risk of prolonged mechanical ventilation at 8, 24, and 48 hrs was higher for patients with a GA or GG genotype at the LT&agr;+250 site and the LT&agr;+250G/TNF−308G haplotype. This association between genotype and duration of mechanical ventilation was more dramatic in patients undergoing conventional coronary artery bypass grafting than in those undergoing off-pump coronary artery bypass grafting. With Bayesian analysis, clinical criteria and genotype can be used sequentially to predict the risk of prolonged mechanical ventilation.ConclusionsThe LT&agr;+250 and LT&agr;+250G/TNF−308G haplotypes are associated with prolonged mechanical ventilation after coronary artery bypass graft. Preoperative genetic screening may guide intraoperative management to reduce postoperative complications.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo determine whether a baseline (random) cortisol concentration <25 &mgr;g/dL in patients with septic shock was a better discriminator of adrenal insufficiency than the standard (250 &mgr;g) and the low-dose (1 &mgr;g) corticotropin stimulation tests as assessed by the hemodynamic response to steroid replacement.SettingIntensive care unit.PatientsFifty-nine patients with septic shock. Their mean age was 57 ± 16.7 yrs; 29 were male.InterventionsA baseline cortisol concentration was obtained. Patients then received an intravenous injection of 1 &mgr;g of corticotropin (low-dose test) followed 60 mins later by an injection of 249 &mgr;g of corticotropin (high-dose test). Cortisol concentrations were obtained 30 and 60 mins after low- and high-dose corticotropin. All patients were administered hydrocortisone (100 mg every 8 hrs) for the first 24 hrs while awaiting results of cortisol assessment. Patients were considered steroid responsive if the pressor agent could be discontinued within 24 hrs of the first dose of hydrocortisone.Measurements and Main ResultsForty-seven percent of patients died. Twenty-two percent of patients met the diagnostic criteria of adrenal insufficiency by the low-dose test and 8% by the high-dose test. However, 61% of patients met the criteria of adrenal insufficiency when we used a baseline cortisol concentration of <25 &mgr;g/dL. Twenty-two patients (37%) were steroid responsive; the baseline serum cortisol was 14.1 ± 5.2 &mgr;g/dL in the steroid-responsive patients compared with 33.3 ± 18 &mgr;g/dL in the steroid-nonresponsive patients (p< .0001). Ninety-five percent of steroid-responsive patients had a baseline cortisol concentration <25 &mgr;g/dL. Fifty-four percent of steroid responders had a diagnostic low-dose test and 22% a diagnostic high-dose test. Receiver operating characteristic curve analysis revealed that a stress cortisol concentration of 23.7 &mgr;g/dL was the most accurate diagnostic threshold for determination of the hemodynamic response to glucocorticoid therapy.ConclusionsAdrenal insufficiency is common in patients with septic shock, the incidence depending largely on the diagnostic test and criteria used to make the diagnosis. There is clearly no absolute serum cortisol concentration that distinguishes an adequate from an insufficient adrenal response. However, we believe that a random cortisol concentration of <25 &mgr;g/dL in a highly stressed patient is a useful diagnostic threshold for the diagnosis of adrenal insufficiency.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ContextBlack families donate at a lower rate than white families. To help develop effective interventions, we compared black and white families’ experiences.ObjectiveTo compare the organ donation request experiences of black and white patients’ families with the hope of identifying factors to better inform consent-rate interventions among blacks.DesignChart reviews were conducted on files of all deceased patients. Audiotaped in-person interviews were conducted with family members, and telephone interviews were conducted with involved healthcare providers and organ procurement organization staff.SettingNine trauma hospitals located in southwest Pennsylvania and northeast Ohio.ParticipantsA sample of 415 families of organ donor–eligible patients (61 black, 354 white).MeasuresMeasures of families’ attitudes about and experiences with donation and transplantation.ResultsWhite families were more likely to be correctly perceived as receptive to donation. Black families viewed as receptive were less likely to be engaged in discussing as many donation-related issues as white families (p< .01). They were also less likely to have spoken to an organ procurement organization representative (p= .024) and were given fewer opportunities to consider the decision with healthcare provider or organ procurement organization staff. Black families had less knowledge about their family member’s wishes, expressed less-favorable attitudes toward organ donation and the health care system, and, finally, were less likely than white families to donate organs (p= .001). A minority of black families (32.8%) knew about the need for more black donors.ConclusionsInterventions to increase consent among blacks need to encourage openness about organ donation within the black community and change healthcare provider and organ procurement organization attitudes and practices toward black families as potential donor families.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveClinical and experimental studies suggest that the proteins of the extracellular actin scavenger system have a role in the pathophysiological processes taking place in critically ill and injured patients. Circulating levels of Gc-globulin and gelsolin are reduced shortly after severe trauma, and admission levels of Gc-globulin are associated with survival. Herein, we sought to measure the association between admission levels of Gc-globulin and postinjury organ dysfunction and infection. We also wanted to describe the serial changes in Gc-globulin in these severely injured patients.DesignProspective cohort.SettingIntensive care unit at a county hospital that serves as a level one trauma center.PatientsNinety-eight consecutive trauma victims admitted to the intensive care unit for >24 hrs during a 4-month period.Measurements and Main ResultsCirculating levels of Gc-globulin were measured by using immunonephelometry. All patients were evaluated daily to obtain the necessary data for assessment of organ dysfunction and sepsis. The median Gc-globulin concentration at admission was 127 mg/L in patients who developed severe multiple organ dysfunction compared with 184 mg/L in patients who did not (p= .001). The admission level of Gc-globulin was comparable to known risk factors such as age and injury severity score, regarding development of organ dysfunction. Plasma concentrations of Gc-globulin remained significantly lower in patients who developed respiratory failure and sepsis, compared with patients who did not develop these complications (p= .02 andp= .015, respectively).ConclusionsAdmission plasma concentration of Gc-globulin is lower in patients who develop organ dysfunction and sepsis after traumatic injury. These data, combined with the work of others, support the hypothesis that actin release and depletion of the extracellular actin scavenger system proteins are associated with, and may contribute in part to, the complications of sepsis and organ dysfunction, particularly respiratory failure and thrombocytopenia.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveNeutropenia recovery may be associated with an increased risk of respiratory function deterioration. A history of pneumonia complicating neutropenia has been identified as the leading cause of adult respiratory distress syndrome during neutropenia recovery in patients receiving anticancer chemotherapy, suggesting that neutropenia recovery may worsen prior lung injury.DesignControlled animal study.SettingResearch laboratory of an academic institution.SubjectsMale Sprague-Dawley rats.InterventionsWe studied the effect of recovery from cyclophosphamide-induced neutropenia on endotoxin (lipopolysaccharide)- or hydrochloric acid-induced acute lung injury in rats. We also studied the effects of adding granulocyte colony-stimulating factor.Measurements and Main ResultsCompared with noncyclophosphamide-treated rats, rats undergoing neutropenia recovery had a higher wet/dry lung weight ratio after hydrochloric acid-induced but not lipopolysaccharide-induced acute lung injury. Granulocyte colony-stimulating factor significantly increased both alveolar cell recruitment (bronchoalveolar lavage fluid counts) and pulmonary edema (wet/dry lung ratio) in both acute lung injury models during neutropenia recovery. Furthermore, in an experiment in hydrochloric acid-instilled rats, exacerbation by granulocyte colony-stimulating factor of hydrochloric acid-induced acute lung injury was inhibited by lidocaine, which prevents adhesion of neutrophils to endothelial cells. Tumor necrosis factor-&agr; and interleukin-1&bgr; concentrations in supernatants of lipopolysaccharide-stimulated alveolar macrophages from rats undergoing neutropenia recovery with granulocyte colony-stimulating factor treatment were significantly increased compared with rats undergoing neutropenia recovery without granulocyte colony-stimulating factor.ConclusionNeutropenia recovery can worsen acute lung injury, and this effect is exacerbated by granulocyte colony-stimulating factor.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveSeveral external stimuli, including trauma, increase the endogenous production of reactive oxygen species that spontaneously attack vital biological molecules. In addition to their direct toxic effects, several secondary messenger systems are induced. To forestall a subsequent organ dysfunction, a short-term posttraumatic down-regulation of granulocyte function has been advocated. Corticosteroids are potent and universal anti-inflammatory agents, but they have well-known side effects. Modulation of the mitogen-activated protein kinase cascade is an alternative approach. The purpose of this study was to investigate how the posttraumatic production of reactive oxygen species can be modulated by hydrocortisone or the extracellular signal-regulated kinase inhibitor U0126.DesignProspective randomized trial.SettingField hospital and research laboratory.SubjectsSeventeen male pigs.InterventionsIn general anesthesia, the pigs were exposed to a standardized insult: one gunshot hitting the right femur from a distance of 25 m, and one pistol shot to the left upper abdomen from close range. Following immediate first aid treatment, the animals were transported to a nearby field hospital. According to randomization, the animals received either hydrocortisone 250 mg intravenously (group 1, n = 9) or a similar amount of saline (group 2, n = 8). The injections were given 5 mins after the last shot. Blood samples were drawn before shooting, immediately before hydrocortisone was given, and 60 mins after shooting. Circulating neutrophils were isolated, and the production of reactive oxygen species was measured fluorometrically. Neutrophils from nine randomly chosen animals (five from group 1 and four from group 2) were treatedin vitrowith the extracellular signal-regulated kinase inhibitor U0126.Measurements and Main ResultsThe injuries as evaluated by the abbreviated injury scale did not differ between the animals. All survived the first 60 mins. While thein vivoproduction of reactive oxygen species tended to increase in the controls, a significant reduction was measured in the hydrocortisone group. Subsequentin vitrotreatment with U0126 further reduced the synthesis of reactive oxygen species by about two thirds in both groups, independently of time.ConclusionsEarly injection of hydrocortisone after trauma inhibits the synthesis of reactive oxygen species from circulating neutrophils. Inhibition of the extracellular signal-regulated kinase branch of the mitogen-activated protein kinase signaling cascade is an alternative approach. The powerfulin vitrocapacity of selective extracellular signal-regulated kinase inhibitors to reduce the posttraumatic reactive oxygen species generation deserves further investigations, and compelling evidence of theirin vivousefulness is still lacking.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo evaluate the efficacy of on-line hemoperfusion for the removal of circulating superantigens in a rat model of streptococcal shock.DesignIn vitroand experimental animal studies.SettingUniversity research laboratories.InterventionsChemically modified polystyrene-based composite fiber reinforced with polypropylene was formulated in discs and used to evaluate the removal of superantigenic toxins from culture supernatantsin vitro, and from bloodin vivo.Measurements and Main ResultsIncubation of streptococcal supernatant with a single disc reduced the concentration of the superantigen streptococcal pyrogenic exotoxin A from 90.9 ± 12.7 ng/mL with the control fiber to 32.5 ± 3.6 ng/mL with active fiber (p< .001). The active discs also brought about a dose-dependent reduction in mitogenic activity that was highly significant (counts reduced from 82,133 ± 2747 using three control discs to 26,307 ± 3547 with three active discs [p< .001]). Beginning 6 hrs after infection, animals were hemoperfused for 3 hrs over columns containing control or active fiber. At the end of the treatment period, there was a significant decrease in the number of circulating bacteria in the active group (3.5 × 104vs. 3.1 × 103colony-forming units/mL,p< .05). However, bacterial counts subsequently increased and by 15 hrs and at all subsequent time points, the number of circulating bacteria was no different between the two groups. There was a highly significant and sustained difference in circulating streptococcal pyrogenic exotoxin A levels between the groups. Streptococcal pyrogenic exotoxin A levels at 9 hrs were 19.9 ng/mL in the controls vs. 2.1 ng/mL in the active group (p= .05). Animals perfused over active fibers had a highly significant survival advantage compared with control or nonperfused groups (p< .01).ConclusionsHemoperfusion and on-line removal of superantigens merits further study as a possible treatment strategy for streptococcal shock syndromes. The mechanism by which the fibers are operating requires further investigation.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo evaluate the effects of a combination of methylene blue, an inhibitor of the nitric oxide pathway, and inhaled nitric oxide on endotoxin-induced acute lung injury in awake sheep.DesignProspective, randomized, controlled experimental study.SettingUniversity animal laboratory.SubjectsTwenty-four yearling, awake sheep.InterventionsThe sheep were anesthetized and instrumented with vascular catheters. After 1 wk of recovery, the animals underwent tracheotomy and were subjected to intravenous infusions ofEscherichia coliendotoxin 10 ng·kg−1·min−1and isotonic saline 3 mL·kg−1·hr−1for 8 hrs. The sheep were randomly assigned to three groups of eight animals each: a) the control group received endotoxin and saline; b) the INO group received endotoxin, saline, and inhaled nitric oxide 40 ppm for 5 hrs; and c) the MB/INO group received endotoxin, saline, and methylene blue 3 mg/kg as an intravenous bolus injection followed by a continuous infusion of 3 mg·kg−1·min−1for 6 hrs in combination with inhaled nitric oxide 40 ppm for 5 hrs.Measurements and Main ResultsHemodynamic variables and blood gases were determined hourly. In the early phase of endotoxemia (0–2 hrs), methylene blue/inhaled nitric oxide reduced the increments in pulmonary arterial pressure, pulmonary microvascular pressure, and pulmonary vascular resistance index by 60% compared with the controls and to a greater extent than did inhaled nitric oxide alone. During the late phase, all the preceding variables returned closely to baseline following inhaled nitric oxide or methylene blue/inhaled nitric oxide but remained remarkably elevated in the control group. Inhaled nitric oxide and methylene blue/inhaled nitric oxide reduced the increase in extravascular lung water by 40% and 80%, respectively. Inhaled nitric oxide transiently attenuated the increase in venous admixture and did not prevent a decrease in arterial oxygenation. In the methylene blue/inhaled nitric oxide group, blood gases remained unchanged from baseline.ConclusionsIn sheep, methylene blue/inhaled nitric oxide protects more efficiently against acute lung injury than inhaled nitric oxide alone, as indicated by a milder pulmonary hypertension, less extravascular lung water accumulation, and maintained gas exchange.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveHypotension and hypoperfusion during septic shock may contribute to tissue hypoxia and the intramyocardial inflammatory response that results in myocardial dysfunction. Therefore, we hypothesized that crystalloid or colloid resuscitation may alter myocardial dysfunction.DesignRandomized, controlled, prospective animal study.SettingUniversity animal laboratory.SubjectsSprague-Dawley rats (250–300 g, n = 6/group).InterventionsRats received an intraperitoneal injection of 10 mg/kg lipopolysaccharide or control. One hour later, rats were randomized to intravenous resuscitation and received either 30 mL/kg normal saline, 10 mL/kg 10% pentastarch, 10 mL/kg 5% rat albumin, or no volume.Measurements and Main ResultsWe measured fractional shortening of cardiomyocytes isolated 5 hrs after lipopolysaccharide or control injection. In separate identical experiments, we measured myocardial interleukin-6, macrophage inhibitory protein-2, and nitric oxide synthase II protein and messenger RNA expression. Control fractional shortening of 24.1 ± 2.2% was decreased by lipopolysaccharide to 18.8 ± 1.2% (p< .001). Volume resuscitation after lipopolysaccharide significantly improved fractional shortening (p< .001). In particular, albumin resuscitation increased fractional shortening to 23.5 ± 0.9%, which was more than either saline (fractional shortening 20.1 ± 1.7%,p< .01) or pentastarch (fractional shortening 21.4 ± 0.9%,p< .01). Myocardial macrophage inhibitory protein-2 protein and interleukin-6 and macrophage inhibitory protein-2 messenger RNA expression and neutrophil content were elevated following lipopolysaccharide (p< .05) but were not altered by volume resuscitation. Myocardial nitric oxide synthase II protein and messenger RNA expression increased following lipopolysaccharide (p< .01) and decreased with albumin resuscitation.ConclusionsWe conclude that following lipopolysaccharide injection, volume resuscitation improves cardiomyocyte fractional shortening. Albumin resuscitation is particularly beneficial in preventing reduced cardiomyocyte contractility, and this benefit may be related to an albumin-induced reduction in nitric oxide synthase II protein and messenger RNA expression following endotoxin injection.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo explore the hypothesis that the survival benefit of mild, therapeutic hypothermia during hemorrhagic shock is associated with inhibition of lipid peroxidation and the acute inflammatory response.DesignProspective and randomized.SettingAnimal research facility.SubjectsMale Sprague-Dawley rats.InterventionsRats underwent pressure-controlled (mean arterial pressure 40 mm Hg) hemorrhagic shock for 90 mins. They were randomized to normothermia (38.0 ± 0.5°C) or mild hypothermia (33–34°C from hemorrhagic shock 20 mins to resuscitation time 12 hrs). Rats were killed at resuscitation time 3 or 24 hrs.Measurements and Main ResultsAll seven rats in the hypothermia group and seven of 15 rats in the normothermia group survived to 24 hrs (p< .05). Hypothermic rats had lower serum potassium and higher blood glucose concentrations at 90 mins of hemorrhagic shock (p< .05). At resuscitation time 24 hrs, the hypothermia group had less liver injury (based on serum concentrations of ornithine carbamolytransferase and liver histology) and higher blood glucose than the normothermia group (p< .05). There were no differences in serum free 8-isoprostane (a marker of lipid peroxidation by free radicals) between the two groups at either baseline or resuscitation time 1 hr. Serum concentrations of interleukin-1&bgr;, interleukin-6, and tumor necrosis factor-&agr; peaked at resuscitation time 1 hr. Tumor necrosis factor-&agr; concentrations were higher (p< .05) at resuscitation time 1 hr in the hypothermia group compared with the normothermic group. Serum cytokine concentrations were not different between survivors and nonsurvivors in the normothermia group. Serum cytokine concentrations returned to baseline values in both groups by 24 hrs. There were no differences in the number of neutrophils in the lungs or the small intestine between the groups. More neutrophils were found in the lungs at resuscitation time 3 hrs than at resuscitation time 24 hrs in both groups (p< .01).ConclusionsThese data suggest that lipid peroxidation and systemic inflammatory responses to hemorrhagic shock are minimally influenced by mild hypothermia, although liver injury is mitigated and survival improved. Other mechanisms of benefit from mild hypothermia need to be explored.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID