摘要:

ObjectiveTo determine whether the administration of lisofylline (1-[5R-hydroxyhexyl]-3,7-dimethylxanthine) would decrease mortality in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).DesignA prospective, randomized, double-blind, placebo-controlled, multicenter study.SettingIntensive care units at 21 hospitals at the ten centers constituting the ARDS Clinical Trials Network.PatientsA total of 235 patients who met eligibility criteria were enrolled in the study (116 into the lisofylline group, 119 into the placebo group).InterventionsPatients were randomized to receive either lisofylline or placebo. The dose of lisofylline was 3 mg/kg with a maximum dose of 300 mg intravenously every 6 hrs. The intravenous solution of study drug was administered over 10 mins every 6 hrs. Dosing was continued for 20 days or until the patient achieved 48 hrs of unassisted breathing.Measurements and Main ResultsThe trial was stopped by the Data Safety Monitoring Board for futility at the first scheduled interim analysis. The patient groups had similar characteristics at enrollment. No significant safety concerns were associated with lisofylline therapy. There was no significant difference between groups in the number of patients who had died at 28 days (31.9% lisofylline vs. 24.7% placebo,p= .215). There was no significant difference between the lisofylline and placebo groups in terms of resolution of organ failures, ventilator-free days, infection-related deaths, or development of serious infection during the 28-day study period. The median number of organ failure–free days for the five nonpulmonary organ failures examined (cardiovascular, central nervous system, coagulation, hepatic, and renal) was not different between the lisofylline and placebo groups. Although lisofylline has been reported to decrease circulating free fatty acid levels, we did not find any such treatment effect compared with placebo.ConclusionsIn this study, there was no evidence that lisofylline had beneficial effects in the treatment of established ALI/ARDS.

ISSN:0090-3493    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo determine the sensitivity, specificity, and predictive values of cultures done with blood drawn through a central venous or arterial catheter compared with peripheral venipuncture.DesignRetrospective cohort study of critically ill surgical patients in whom samples for paired cultures were drawn through a central venous or arterial catheter and peripheral venipuncture.SettingTertiary-care, university-affiliated medical center.PatientsTwo hundred seventy-one patients hospitalized on a surgical and a cardiothoracic intensive care unit between November 1994 and August 1997.InterventionsNone.Measurements and Main ResultsBlinded assessments of culture results done by two physicians were used as the gold standard. Sensitivity, specificity, and positive and negative predictive values were compared for culture of blood from catheters and culture of blood from peripheral venipuncture. Of 499 observations, 426 were catheter-negative/venipuncture-negative, 19 were catheter-positive/venipuncture-positive, 18 were catheter-negative/venipuncture-positive, and 36 were catheter-positive/venipuncture-negative pairs. For catheter draws compared with peripheral venipuncture, sensitivity was 78% (confidence interval [CI], 65% to 90%) and 65% (CI, 50% to 79%) (p= .2), specificity was 95% (CI, 94% to 97%) and 98% (CI, 97% to 99%) (p= .002), positive predictive value was 63% (CI, 51% to 76%) and 78% (CI, 64% to 91%) (p= .1) and negative predictive value was 98% (CI, 96% to 99%) and 97% (CI, 95% to 98%) (p= .3). When central venous specimens as differentiated from arterial catheter specimens were compared with peripheral venipuncture, the difference between positive predictive values reached statistical significance (61% and 82%;p= .04).ConclusionsIn critically ill surgical patients, cultures of blood drawn through a catheter are less specific than those obtained from a peripheral venipuncture. Both types of cultures have an excellent negative predictive value. Positive predictive value of cultures of blood drawn through a catheter is low and, when obtained from a central line, statistically less than from a peripheral venipuncture. Additional cultures seem to be necessary for the proper interpretation of a positive culture drawn through a catheter in critical care patients.

ISSN:0090-3493    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo examine the effects of pharmacologic agents designed to limit burn-mediated calcium overload on cardiomyocyte [Ca2+] and cardiac contractile function.DesignExperimental, comparative study.SettingCellular biology and physiology laboratory.SubjectsAdult Sprague Dawley rats.InterventionsRats were given third-degree burn injury over 40% of the total body surface area, were fluid resuscitated, and then were divided randomly to receive one of five treatments: vehicle (normal saline); amiloride (50 mg/kg) to inhibit H+-Na+exchange and subsequent Na+-Ca2+exchange; dantrolene (10 mg/kg, 30 mins, 6 and 22 hrs postburn) to inhibit sarcoplasmic reticulum Ca2+release; diltiazem (10 mg/kg given over first 6 hrs postburn); or amlodipine (0.07 mg/kg, 24 hrs preburn and 30 mins postburn) to block calcium slow channels. Appropriate controls (sham burns given the appropriate pharmacologic agent) were included in each group. Twenty-four hrs postburn, left ventricular function (Langendorff), cardiomyocyte [Ca2+]iand [Na+]imeasured by fura-2-AM or sodium-binding benzofurzan isophthalate loading of cardiomyocytes, and myocyte secretion of tumor necrosis factor-&agr; (enzyme-linked immunosorbent assay) were assessed in shams and burns from each experimental group. This time point was selected based on our previous work confirming maximal ventricular contractile defects and maximal cytokine secretion 24 hrs postburn.Measurements and Main ResultsBurn trauma increased myocyte [Ca2+]iand [Na+]i, promoted tumor necrosis factor-&agr; secretion by cardiomyocytes, and impaired left ventricular function. All pharmacologic agents reduced the burn-mediated Ca2+/Na+accumulation in cardiomyocytes and ablated burn-mediated tumor necrosis factor-&agr; secretion by myocytes; in contrast, dantrolene and amiloride provided significantly greater cardioprotection than pharmacologic agents that specifically targeted Ca2+slow channels (diltiazem and amlodipine).ConclusionOur data suggest that the calcium antagonists used in this study provide cardioprotection by modulating several aspects of the overall inflammatory cascade rather than solely limiting cardiomyocyte accumulation of calcium.

ISSN:0090-3493    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo determine whether endogenous lipoproteins can abrogate the host response to lipopolysaccharide (LPS)in vivo.DesignRandomized, placebo-controlled study.SettingUrban public hospital with academic affiliation.SubjectsEighteen healthy, normolipidemic, normal weight volunteers, 21–35 yrs of age.InterventionsFasting and postprandial (hypertriglyceridemic) subjects were injected with endotoxin (LPS, Lot EC-5, 4 ng/kg = 20 endotoxin units/kg) as either a bolus or following preincubation of the LPS with autologous whole blood vs. saline. In addition, LPS-induced cytokine production was determinedex vivoto examine the capacity of fasting vs. hypertriglyceridemic whole blood to attenuate the effect of large, potentially lethal concentrations of LPS in humans.MeasurementsVital signs were recorded and serial blood samples analyzed for changes in white blood cell count, cytokine, and stress hormone levels over 24 hrs. The distribution of lipoproteins in fasting and postprandial blood after preincubation was determined using125I-LPS.Main ResultsEndogenous lipoproteins abrogated the host response to LPSin vivo, but only after preincubation with the LPS. Peak oral temperature (p< .05) and white blood cell count (p< .05), and plasma tumor necrosis factor (TNF)-&agr; (p< .01) and adrenocorticotropic hormone levels (p< .03) were significantly reduced in volunteers injected with LPS preincubated with whole blood vs. LPS preincubated with saline. Approximately 80% of the LPS was bound to lipoproteins after preincubation with either fasting or hypertriglyceridemic blood. Thus, protection was associated with lipoprotein binding. In addition, hypertriglyceridemic but not fasting blood inhibited theex vivoTNF-&agr; response to large, highly toxic doses of LPS (p< .05). Without the preincubation of lipoproteins with LPS, there was a trend for an exaggerated clinical and TNF-&agr; response in the hypertriglyceridemic subjects.ConclusionPreincubation of LPS with whole blood promotes lipoprotein-LPS binding and is associated with an attenuated response to this toxic macromolecule. Although the clinical relevance of these data requires further elucidation, our results continue to support a lipid-based therapeutic strategy to combat Gram-negative sepsis.

ISSN:0090-3493    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveA biallelic polymorphism within the human interleukin (IL)-6 gene promoter region (−174 G/C) has been shown to affect IL-6 transcriptionin vitroand IL-6 plasma levels in healthy adults. Because IL-6 is excessively released into the circulation during sepsis and closely correlates with the clinical course, we studied whether this promoter polymorphism has an effect on the incidence and/or outcome of sepsis.DesignPopulation-based association study in critically ill patients and healthy controls.SettingSurgical intensive care unit (ICU) in a German university hospital.PatientsSurgical patients (n = 326) of German Caucasian origin with an ICU stay of at least 3 days admitted between 1997 and 1999 were prospectively enrolled. In a subset of 50 patients, sepsis was diagnosed according to consensus criteria (American College of Chest Physicians 1992). Healthy sex-matched adults of the same ethnic and geographic background served as controls.InterventionsBlood sampling.Measurements and Main ResultsThe (−174 G/C) polymorphism was genotyped by an allele-specific polymerase chain reaction. IL-6 plasma levels were determined by enzyme-linked immunosorbent assay. Genotype distribution and allele frequencies did not differ significantly between patients with or without sepsis and healthy controls. In patients who finally succumbed to sepsis, significantly less GG homozygotes were observed compared with survivors (p= .008). Median systemic IL-6 levels in septic patients closely correlated with outcome (p< .0001) but were not associated with the IL-6 promoter genotype.ConclusionsThe IL-6 promoter polymorphism (−174 G/C) does not affect the incidence of sepsis. However, the GG homozygous genotype is significantly associated with an improved survival in sepsis. Because this association is independent from the systemic IL-6 response, we suggest that other genetically linked polymorphisms may be the primary cause.

ISSN:0090-3493    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundCardiopulmonary bypass predisposes the splanchnic region to inadequate perfusion and increases in gut permeability. Related to these changes, circulating endotoxin has been shown to rise during cardiac surgery, and may contribute to cytokine activation, high oxygen consumption, and fever (“postperfusion syndrome”). To a large extent, free endotoxin in the gut is a product of the proliferation of aerobic Gram-negative bacteria and may be reduced by nonabsorbable antibiotics.Objective.To evaluate the effect of preoperative selective gut decontamination (SGD) on the incidence of endotoxemia and cytokine activation in patients undergoing open heart surgery.DesignProspective, randomized, placebo-controlled double-blind trial.SettingTertiary-care university teaching hospital.InterventionPreoperative administration for 5 to 7 days of oral nonabsorbable antibiotics (polymyxin B and neomycin) vs. placebo. The efficacy of SGD was assessed by culture of rectal swabs.PatientsForty-four patients (median age 65 yrs, 29 males) were included in a pilot study to establish the sampling points of perioperative measurements. Seventy-eight consecutive patients (median age 65 yrs, 55 males) were enrolled for the prospective study; of these, 51 were randomly allocated to take SGD (n = 24) or placebo (n = 27); 27 were included in a control group (no medication).Measurements and ResultsSGD but not placebo effectively reduced the number of rectal swabs that grew aerobic Gram-negative bacteria (27% vs. 93%, respectively;p< .001). SGD did not affect the occurrence of perioperative endotoxemia, nor did it reduce the tumor necrosis factor-&agr;, interleukin-10, or interleukin-6 concentrations (p> .20), as determined before surgery, upon aorta declamping, 30 mins into reperfusion, or 2 hrs after surgery. Also, SGD did not alter the incidence of postoperative fever or clinical outcome measures such as duration of artificial ventilation and intensive care unit and hospital stay.ConclusionSGD effectively reduces the aerobic Gram-negative bowel flora in cardiac surgery patients but fails to affect the incidence of perioperative endotoxemia and cytokine activation during cardiopulmonary bypass and the occurrence of a postperfusion syndrome.

ISSN:0090-3493    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo verify the hypothesis that the gastric intraluminal Pco2(Pgco2) changes independently of the change in cardiac output (CO) during and after cardiovascular surgery using cardiopulmonary bypass (CPB), and that the elevation of Pgco2affects the patients’ morbidity.DesignProspective, noninterventional study.SettingMedical/surgical intensive care unit and operating theater of a university hospital.PatientsSixteen adults patients receiving elective cardiovascular surgery using CPB.InterventionsNone.Measurements and Main ResultsAfter induction of anesthesia, the patients were fitted with a gastric tube equipped at the tip with a CO2sensor (ion-selective field effect transistor) that can continuously measure real-time Pgco2, and a pulmonary artery catheter capable of monitoring continuous CO (CCO) and end-tidal CO2. Data from the devices was uploaded to a personal computer every 2 mins until the catheter was pulled off based on clinical judgment (Pgco2values were blinded to everyone except the investigator). One patient expired as a result of multiple organ failure subsequent to sepsis, and postoperative morbidity assessed by the peak SOFA (sequential organ failure assessment) score (mean ± sd 6.9 ± 3.5; range, 2–13) was correlated with the peak Pgco2during intensive care unit stay (mean ± sd 74.1 ± 30.7 mm Hg; range, 45–169 mm Hg) (p< .01, by regression analysis). The peak Pgco2during surgery (mean ± sd 71.1 ± 18.1 mm Hg; range, 44–115 mm Hg) had no correlation with the postoperative morbidity. From analysis of CCO before, during, and after returning from the above 60 mm Hg of Pgco2, Pgco2changed independently of CCO.ConclusionsPgco2changed independently of CCO, and its postoperative elevation was related to morbidity, even in the group of patients with a good outcome. Continuous monitoring of Pgco2is useful for the detection of morbidity and can be expected to help elucidate the pathophysiology of change of Pgco2.

ISSN:0090-3493    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveThe method of determining continuous cardiac output (CO) with beat-to-beat pulse-contour analysis calibrated by transthoracic thermodilution is gaining much wider clinical acceptance. However, some questions have been raised regarding the reliability of this method during periods of profound hemodynamic instability. We validated the original calculation of pulse-contour analysis and a new, improved algorithm against thermodilution-derived measurements of CO in patients with changes of CO >20%.DesignComparative study.SettingCardiac surgical intensive care unit of a university hospital.PatientsTwenty-four patients after cardiac surgery who experienced changes of CO >±20% during their postoperative course.InterventionsCO was measured by transthoracic thermodilution and pulse-contour analysis (PiCCO, PULSION Medical Systems, Munich, Germany) at serial intervals every 60 mins during study periods of 8–44 hrs. During this time, no recalibration of the pulse-contour computer was performed.Measurements and Main ResultsA total of 517 simultaneous measurements of thermodilution CO and pulse-contour CO measured by the two different algorithms were compared by regression, structural regression, and Bland-Altman analyses. Mean change of CO was 40% ± 27% (range, 20% to 139%), range of systemic vascular resistance was 450–2360 dyne·sec/cm5. Correlation of the original pulse-contour algorithm to thermodilution CO wasr= .76, withp= .027; bias was 0.08 L/min, with 1.8 L/min single sd. Correlation of the improved pulse-contour algorithm to thermodilution CO wasr= .88, withp= .0001; bias was 0.2 L/min, with 1.2 L/min single sd. Mean CO by the new pulse-contour algorithm did not differ significantly from CO by thermodilution during the study period. The difference between the methods was not influenced by variations of heart rate or arterial pressure.ConclusionsCO measurement by arterial pulse-contour analysis based on a new, improved algorithm is reliable, even in patients with profound changes of CO and during periods of hemodynamic instability.

ISSN:0090-3493    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveThe purpose of the study was to determine whether an education initiative aimed at improving central venous catheter insertion and care could decrease the rate of primary bloodstream infections.DesignPre- and postintervention observational study.SettingEighteen-bed surgical/burn/trauma intensive care unit (ICU) in an urban teaching hospital.PatientsA total of 4,283 patients were admitted to the ICU between January 1, 1998, and December 31, 2000.InterventionsA program primarily directed toward registered nurses was developed by a multidisciplinary task force to highlight correct practice for central venous catheter insertion and maintenance. The program consisted of a 10-page self-study module on risk factors and practice modifications involved in catheter-related infections as well as a verbal in-service at staff meetings. Each participant was required to take a pretest before taking the study module and an identical test after its completion. Fact sheets and posters reinforcing the information in the study module were also posted throughout the ICU.Measurements and Main ResultsSeventy-four primary bloodstream infections occurred in 6874 catheter days (10.8 per 1000 catheter days) in the 18 months before the intervention. After the implementation of the education module, the number of primary bloodstream infections fell to 26 in 7044 catheter days (3.7 per 1000 catheter days), a decrease of 66% (p< .0001). The estimated cost savings secondary to the decreased infection rate for the 18 months after the intervention was between $185,000 and $2.808 million.ConclusionsA focused intervention primarily directed at the ICU nursing staff can lead to a dramatic decrease in the incidence of primary bloodstream infections. Educational programs may lead to a substantial decrease in cost, morbidity, and mortality attributable to central venous catheterization.

ISSN:0090-3493    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectivesThe catabolic state is a major contributor to morbidity and mortality of critical illness and may be related to endocrine changes. We studied whether protein and lipid turnover correlate with insulin and growth and thyroid hormone plasma levels in critically ill infants.DesignProspective clinical study.SettingPediatric intensive care unit.PatientsTwelve critically ill children and ten age-matched controls.MeasurementsWe measured lipolysis and protein turnover by infusing albumin-bound uniformly13C palmitic acid and2H3-leucine for 3 hrs and2H5-glycerol for 5 hrs to critically ill infants. Simultaneously, we measured serum growth hormones, insulin, C-peptide, thyroid-stimulating hormone, T4, T3, albumin, retinol binding protein (RBP), and prealbumin. Hormone and serum protein levels were also measured in six children when recovered from critical illness. Ten healthy age-matched children served as controls for hormone serum levels comparison.ResultsPalmitic acid and glycerol turnover were 5.6 ± 2.2 &mgr;mol/kg/min and 12.2 ± 7.3 &mgr;mol/kg/min, respectively, whereas &agr;-ketoisocaproic turnover was 4.9 ± 2.8 &mgr;mol/kg/min. &agr;-Ketoisocaproic turnover positively correlated (R= 0.7,p= .03) with duration of pediatric intensive care unit admission and with prealbumin and RBP serum levels (R= 0.9,p= .001). Insulin-like growth factor binding protein (IGFBP)-2 was significantly higher and IGFBP-3 was significantly lower in critically ill children (p= .03 andp= .04 vs. recovery phase, respectively). No other hormonal differences were found. Serum albumin was significantly lower in sick children. We found a significant correlation between prealbumin and RBP and IGFBP-3 (R= 0.6,p= 0.03 andR= 0.6,p= .04, respectively). &agr;-Ketoisocaproic turnover positively correlated with IGFBP-1 (R= 0.79,p= .01) and did not correlate with insulin-like growth factor I (R= −0.5,p= .15 [ not significant]) No other correlations were found. Lipid turnover measurements did not correlate with any endogenous hormone levels or with duration of critical illness.ConclusionProtein turnover but not lipolysis correlated with a persisting critically ill condition, serum prealbumin, RBP, and plasma IGFBP-1.

ISSN:0090-3493    

出版商:OVID    

年代:2002

数据来源: OVID