ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveExpression of inflammatory mediators is controlled in part at the transcriptional level via nuclear factor-&kgr;B. Inhibition of nuclear factor-&kgr;B activation may be beneficial in critically ill patients.N-acetylcysteine is an antioxidant that inhibits nuclear factor-&kgr;B activationin vitro. In this pilot study we investigated the effect ofN-acetylcysteine on nuclear factor-&kgr;B activation and circulating cytokine and adhesion molecules in patients with sepsis.DesignProspective, randomized, double blind, placebo-controlled pilot trial.SettingEight-bed intensive care unit in a university teaching hospital.PatientsTwenty consecutive patients within 12 hrs of fulfilling the consensus criteria for sepsis.InterventionsA bolus of 150 mg/kgN-acetylcysteine in 100 mL of 0.9% saline over 15 mins, then 50 mg/kg in 100 mL of 0.9% saline over 4 hrs as a loading dose, and then a maintenance infusion of 50 mg/kg in 200 mL of 0.9% saline over each 24-hr period for a total of 72 hrs, or an equivalent volume of saline.Measurements and Main ResultsNuclear factor-&kgr;B activation was measured in mononuclear leukocytes using electrophoretic mobility shift assay, at baseline and 24, 48, 72, and 96 hrs later. Activation decreased significantly in patients treated withN-acetylcysteine (p= .016) but not placebo and was significantly reduced at 72 hrs compared with both preinfusion values (p= .028) and patients receiving placebo (p= .01). Plasma interleukin-6, interleukin-8, and soluble intercellular adhesion molecule-1 concentrations were measured using enzyme immunoassay. Interleukin-6 concentrations were high initially and then decreased in all patients, regardless of whether they receivedN-acetylcysteine or placebo. Interleukin-8 decreased significantly only in those who receivedN-acetylcysteine (p= .0081). Soluble intercellular adhesion molecule-1 concentrations remained unchanged in all patients.ConclusionsAdministration ofN-acetylcysteine results in decreased nuclear factor-&kgr;B activation in patients with sepsis, associated with decreases in interleukin-8 but not interleukin-6 or soluble intercellular adhesion molecule-1. These pilot data suggest that antioxidant therapy withN-acetylcysteine may be useful in blunting the inflammatory response to sepsis. Further studies are warranted.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo develop a simple score to help assess the presence or absence of infection in critically ill patients using routinely available variables.DesignObservational study of a prospective cohort of patients divided into a developmental set (n = 353) and a validation set (n = 140).SettingDepartment of intensive care at an academic tertiary care center.PatientsFour hundred and ninety-three adult patients admitted to the intensive care unit for ≥24 hrs.InterventionsNone.Measurements and Main ResultsThe presence of infection was defined using the Centers for Disease Control definitions. Body temperature, heart rate, respiratory rate, white blood cell count, and C-reactive protein concentrations were measured, and the Sequential Organ Failure Assessment score was calculated throughout the intensive care unit stay. Infection was documented in 92 of the 353 patients (26%) in the developmental set and in 41 of the 140 patients (29%) in the validation set. Univariate logistic regression was used to select significant predictors for infection. Each continuous predictor was transformed in a categorical variable using a robust locally weighted least square regression between infection and the continuous variable of interest. When more than two cate-gories were created, the variable was separated into iso-weighted dummy variables. A multiple logistic regression model predicting infection was calculated with all the variables coded 1 or 0 allowing for relative scoring of the different predictors. The resulting Infection Probability Score consisted of six different variables and ranged from 0 to 26 points (0–2 for temperature, 0–12 for heart rate, 0–1 for respiratory rate, 0–3 for white blood cell count, 0–6 for C-reactive protein, 0–2 for Sequential Organ Failure Assessment score).The best predictors for infection were heart rate and C-reactive protein, whereas respiratory rate was found to have the poorest predictive value. The cutoff value for the Infection Probability Score was 14 points, with a positive predictive value of 53.6% and a negative predictive value of 89.5%. Model performance was very good (Hosmer-Lemeshow statistic,p= .918), and the areas under receiver operating characteristic curves were 0.820 for the developmental set and 0.873 for the validation set.ConclusionsThe Infection Probability Score is a simple score that can help assess the probability of infection in critically ill patients. The variables used are simple, routinely available, and familiar to clinicians. Patients with a score <14 points have only a 10% risk of infection.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveThe purposes of the present study were to evaluate the induction of heat shock protein (HSP) 70 expression in the diaphragm by geranylgeranylacetone (GGA) administration and to determine the effect of HSP70 induction on diaphragm contractility measuredin vitroand the production of oxygen-derived free radicals during experimental septic peritonitis.DesignProspective laboratory study.SettingUniversity laboratory.SubjectsOne-hundred sixty male Wistar rats.InterventionsIn experiment 1, rats received GGA intragastrically, and time-dependent induction of HSP70 expression in the diaphragm was determined at 0, 12, 24, and 36 hrs after GGA administration. To evaluate dose-dependent inhibition of GGA-induced HSP70 expression by quercetin, rats were pretreated with progressive doses of quercetin before GGA administration. In experiment 2, rats received gum arabic solution (vehicle), 100, 200, or 400 mg/kg of GGA. In experiment 3, rats were pretreated with quercetin or glycerol before GGA or vehicle administration. Intra-abdominal sepsis was induced by cecal ligation and perforation (CLP) under inhalation anesthesia after GGA or vehicle administration in experiments 2 and 3.Measurements and Main ResultsWestern blot analysis using diaphragm homogenates obtained from normal rats showed that HSP70 expression peaked at 24 or 36 hrs after GGA administration and that pretreatment with >10 mg/kg of quercetin blocked the induction of HSP70 expression by GGA. CLP induced diaphragmatic dysfunction and increased diaphragmatic malondialdehyde concentrations and superoxide dismutase and glutathione peroxidase activities. GGA attenuated CLP-induced diaphragm dysfunction and increased malondialdehyde concentrations in a dose-dependent manner but did not affect superoxide dismutase and glutathione peroxidase activities after CLP. Diaphragm dysfunction and increased diaphragmatic malondialdehyde concentrations after CLP were maintained on quercetin pretreatment despite GGA administration.ConclusionsGGA induces HSP70 expression in the diaphragm, and this induction attenuates septic diaphragm impairment by inhibiting the production of oxygen-derived free radicals.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivePositive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs) may partially reverse atelectasis and reduce ventilation-associated lung injury. The purposes of this study were to assess a) magnitude and duration of RM effects on arterial oxygenation and on requirements for oxygenation support (Fio2/PEEP) in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) receiving ventilation with low tidal volumes and high levels of PEEP; and b) frequency of adverse respiratory and circulatory events attributable to RMs.DesignProspective, randomized, crossover study.SettingThirty-four intensive care units at 19 hospitals.PatientsSeventy-two patients with early ALI/ARDS. Baseline PEEP and Fio2were 13.8 ± 3.0 cm H2O and 0.39 ± 0.10, respectively (mean ± sd).InterventionsWe conducted RMs by applying continuous positive airway pressure of 35–40 cm H2O for 30 secs. We conducted sham RMs on alternate days. We monitored oxyhemoglobin saturation by pulse oximetry (SpO2), Fio2/PEEP, blood pressure, and heart rate for 8 hrs after RMs and sham RMs. We examined chest radiographs for barotrauma.Measurements and Main ResultsResponses to RMs were variable. Greatest increments from baseline SpO2within 10 mins after RMs were larger than after sham RMs (1.7 ± 0.2 vs. 0.6 ± 0.3 %, mean ± sem,p< .01). Systolic blood pressure decreased more within 10 mins after RMs (9.4 ± 1.1 vs. 3.1 ± 1.1 mm Hg,p< .01). Changes in Fio2/PEEP requirements were not significantly different at any time after RMs vs. sham RMs. Barotrauma was apparent on first radiographs after one RM and one sham RM.ConclusionsIn ALI/ARDS patients receiving mechanical ventilation with low tidal volumes and high PEEP, short-term effects of RMs as conducted in this study are variable. Beneficial effects on gas exchange in responders appear to be of brief duration. More information is needed to determine the role of recruitment maneuvers in the management of ALI/ARDS.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo determine the significance of moderate elevations of serum troponin I in a surgical intensive care unit patient population in terms of its impact on indexes of outcome including mortality, morbidity, and hospital and intensive care unit length of stay.DesignRetrospective chart review and analysis of clinical data.SettingA surgical intensive care unit at a tertiary care hospital.PatientsFrom the 27-month surgical intensive care unit database of admissions, 869 patients with serum troponin I determinations during their admission were identified. Patients who had cardiac surgery were excluded.InterventionsNone.Measurements and ResultsPatients were divided into four groups based on their maximum serum troponin I concentrations. Hospital mortality, incidence of myocardial infarction, and hospital and intensive care unit length of stays were compared. Patients with moderate elevations of serum troponin I (0.4–2.0 &mgr;g/L) had a significantly higher mortality rate (chi-square = 32.57,p< .0001) and longer length of intensive care unit and hospital stays (p< .0005) when compared with patients without similar elevations. Within the range of moderately elevated troponin concentrations, higher titers were associated with increasing mortality risk, longer hospital and intensive care unit stays, and a higher incidence of myocardial infarction. The use of a &bgr;-blocker and aspirin was associated with better survival for patients with maximum serum troponin concentrations ≥2 &mgr;g/L.ConclusionModerate elevations of serum troponin I, which are below the threshold required to diagnose overt myocardial infarction, may reflect ongoing myocardial injury in the critically ill and are associated with a higher mortality rate and longer hospital and intensive care unit length of stays. The use of &bgr;-blockers and aspirin is associated with better outcomes for this subset of patients.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveWith many mechanical ventilators, it is possible to modify the time to reach the selected airway pressure and the criteria for cycling off the inflation during pressure support ventilation. This study evaluated the effect of different inspiratory rise time and cycling off criteria on breathing pattern and work of breathing.DesignClinical study.SettingUniversity laboratory.PatientsTen intubated patients recovering from acute lung injury (Pao2/Fio2245 ± 26 torr, positive end-expiratory pressure 9 ± 3 cm H2O).InterventionsWe studied two inspiratory rise time criteria (shortest and longest, 0% and 40% of the breath cycle time) and two cycling off criteria (lowest and highest, 5% and 40% of the peak inspiratory flow) at 5 and 15 cm H2O of pressure support. Respiratory rate, tidal volume, and inspiratory and expiratory work of breathing (WOBIand WOBE) were measured.Measurements and Main ResultsAt both levels of pressure support ventilation, the shortest inspiratory rise time significantly reduced the WOBIfrom 0.77 ± 0.32 to 0.56 ± 0.23 J/L and from 0.24 ± 0.28 to 0.08 ± 0.09 J/L without affecting respiratory rate or tidal volume.At 15 cm H2O of pressure support ventilation, the lowest cycling off criteria significantly reduced respiratory rate from 24.9 ± 12.1 to 21.5 ± 12.7 beats/min and increased tidal volume from 0.51 ± 0.17 to 0.60 ± 0.26 L. At both levels of pressure support ventilation, the modification of cycling off criteria did not influence WOBIand WOBE.ConclusionsOur results suggest that in patients recovering from acute lung injury during pressure support ventilation, a) the shortest inspiratory rise time reduces the WOBI; and b) at 15 cm H2O of pressure support ventilation, the lowest cycling off criteria reduces the respiratory rate and increases the tidal volume without modifying the WOBIand WOBE. Modifications of inspiratory rise time and cycling off criteria must be carefully adjusted during pressure support ventilation.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo investigate the confounding effects of age, gender, serum creatinine, and electrolyte concentrations on plasma B-type natriuretic peptide (BNP) concentrations in critically ill patients.DesignA prospective cross-sectional study.SettingA 20-bed general intensive care unit of a tertiary referral hospital.PatientsPatients were 121 patients admitted to the intensive care unit over a period of 9 wks.InterventionsIntravenous blood was collected for BNP measurements, and cardiac investigations including echocardiography were carried out for every patient on admission.Measurements and Main ResultsThe mean BNP concentration was 201 ± 317 pg/mL (n = 121). Thirty-five patients (28.9%), identified to have cardiac abnormalities, exhibited higher BNP concentrations than those without cardiac abnormalities (518 ± 394 vs. 60 ± 98 pg/mL,p< .001). The females exhibited higher concentrations of BNP than males in the noncardiac abnormality group (96 ± 132 pg/mL, n = 39 vs. 31 ± 38 pg/mL, n = 47,p= .016). BNP correlated significantly with age (r2= .19) and creatinine (r2= .084). The latter correlation became insignificant when patients with cardiac abnormality were excluded. No correlation was found between serum Na+and K+concentrations with BNP. Multivariate analyses demonstrated that the presence of cardiac abnormalities accounted for nearly 50% of the BNP variation. Addition of age and gender improved R2to 60%. The contribution of creatinine was found to be insignificant. There was no association between BNP concentrations and serum Na+and K+concentrations. Logistic analysis confirmed that BNP is the strongest predictor for cardiac abnormalities in the critically ill patients.ConclusionThe current study demonstrated that plasma BNP concentrations increased with age and were higher in females than in males. Although the presence of cardiac disease was the most important determinant for BNP variations, age and gender also contributed significantly. The results suggest that age and gender need to be taken into account in the interpretation of BNP concentrations in critically ill patients.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo compare performance of flow-adapted compensation of endotracheal tube resistance (automatic tube compensation, ATC) between the original ATC system and ATC systems incorporated in commercially available ventilators.DesignBench study.SettingUniversity research laboratory.SubjectsThe original ATC system, Dräger Evita 2 prototype, Dräger Evita 4, Puritan-Bennett 840.InterventionsThe four ventilators under investigation were alternatively connected via different sized endotracheal tubes and an artificial trachea to an active lung model. Test conditions consisted of two ventilatory modes (ATC vs. continuous positive airway pressure), three different sized endotracheal tubes (inner diameter 7.0, 8.0, and 9.0 mm), two ventilatory rates (15/min and 30/min), and four levels of positive end-expiratory pressure (0, 5, 10, and 15 cm H2O).Measurements and Main ResultsPerformance of tube compensation was assessed by the amount of tube-related (additional) work of breathing (WOBadd), which was calculated on the basis of pressure gradient across the endotracheal tube. Compared with continuous positive airway pressure, ATC reduced inspiratory WOBaddby 58%, 68%, 50%, and 97% when using the Evita 4, the Evita 2 prototype, the Puritan-Bennett 840, and the original ATC system, respectively. Depending on endotracheal tube diameter and ventilatory pattern, inspiratory WOBaddwas 0.12–5.2 J/L with the original ATC system, 1.5–28.9 J/L with the Puritan-Bennett 840, 10.4–21.0 J/L with the Evita 2 prototype, and 10.1–36.1 J/L with the Evita 4 (difference between each ventilator at identical test situations,p< .025). Expiratory WOBaddwas reduced by 5%, 26%, 1%, and 70% with the Evita 4, the Evita 2 prototype, the Puritan-Bennett 840, and the original ATC system, respectively. The expiratory WOBaddcaused by an endotracheal tube of 7.0 mm inner diameter was 5.5–42.2 J/L at a low ventilatory rate and 19.6–82.3 J/L at a high ventilatory rate. It was lowest with the original ATC system and highest with the Evita 4 ventilator (p< .025).ConclusionsFlow-adapted tube compensation by the original ATC system significantly reduced tube-related inspiratory and expiratory work of breathing. The commercially available ATC modes investigated here may be adequate for inspiratory but probably not for expiratory tube compensation.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID