摘要:

ObjectiveTo determine the efficacy and safety of using natural platelet-activating factor receptor antagonist (PAFra), BN 52021, to treat patients with severe Gram-negative bacterial sepsis.DesignA prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial.SettingFifty-nine academic medical center intensive care units in Europe.PatientsSix hundred nine patients with severe sepsis, suspected to be related to Gram-negative bacterial infection, who received PAFra or placebo.InterventionsPatients were randomized to receive either a dose of PAFra (120 mg iv) every 12 hrs over a 4-day period or placebo over a 4-day period.Measurements and Main ResultsThe patients were well matched at study entry for severity of illness and for risk factors known to influence the outcome of sepsis. Among all randomized patients, the 28-day, all-cause mortality rate was 49% (152/308) in the placebo group, and 47% (140/300) in the PAFra group (p = .50). When analyzed on the basis of the previously defined target population, the 28-day, all-cause mortality rate was 50% (115/232) in the placebo group and 44% (94/212) in the PAFra group, yielding a 12% reduction in mortality rate (p = .29). In patients with documented infection involving other organisms, there was no difference between treated and placebo groups. When the outcomes of organ dysfunctions were examined in the overall population and in the documented Gram-negative bacterial infection population, the number of patients who resolved hepatic dysfunction tended to be higher in the treated group than in the placebo group (p = .06). The number of adverse events reported were not different between the two groups.ConclusionsA 4-day administration of the studied PAFra (BN 52021) failed to demonstrate a statistically significant reduction in the mortality rate of patients with severe sepsis suspected to be related to Gram-negative bacterial infection. If PAFra treatment has any therapeutic activity in severe Gram-negative bacterial sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial. (Crit Care Med 1998; 26:1963-1971)

ISSN:0090-3493    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo evaluate the effects of hyperbaric oxygen (HBO) therapy on zymosan-induced shock in rats. Zymosan, a cell wall component of the yeast Saccharomyces cerevisiae, induces inflammation by causing the production of various cytokines and pro-inflammatory mediators. The administration of zymosan to rats represents a new experimental shock model by inducing acute peritonitis, severe hypotension, and signs of systemic illness. However, it has been recently proposed that the zymosan-induced shock, like septic shock, may be mediated by overproduction of nitric oxide.DesignExperimental study.SettingInstitute of Pharmacology and Toxicology, 2ndUniversity of Naples, Naples, Italy.SubjectsMale rats were treated with zymosan (500 mg/kg) by intraperitoneal route, with HBO (2 Absolute Atmosphere) or with zymosan and HBO (2 Absolute Atmosphere).Measurements and Main ResultsPeritoneal exudate, plasma, and peritoneal nitric oxide metabolites (NOx) and zymosan determined a time-dependent increase in peritoneal and plasma NOx concentrations, and peritoneal leukocytes were determined. Moreover, symptomatology was observed.The administration of zymosan caused the appearance of a severe illness in the rats characterized by ruffled fur, lethargy, conjunctivitis, diarrhea, and a significant loss of body weight.All zymosan-treated rats developed an acute peritonitis, producing turbid exudate. Zymosan determined a time-dependent increase in peritoneal, plasma NOx, and tumor necrosis factor (TNF)-alpha concentrations. Morbidity of zymosan shocked rats has been attenuated and no mortality was observed by treatment with HBO. These findings were associated with a significant reduction either of peritoneal leukocytes and exudate, or plasma and peritoneal NOx concentrations. Moreover, TNF-alpha levels were significantly reduced in animals shocked by zymosan and treated with HBO.ConclusionsOur findings suggest that HBO may also be an efficacious treatment in zymosan-induced experimental shock model. (Crit Care Med 1998; 26:1972-1976)

ISSN:0090-3493    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectivesTo address the following issues regarding the use of prone position ventilation in patients with severe acute respiratory distress syndrome (ARDS): a) response rate; b) magnitude and duration of improved oxygenation in responders during a 12-hr trial and the consequences of returning to the supine position; c) effects of the prone position on gas exchange and hemodynamics; d) consequences of oxygenation in nonresponders; and e) effects of repeated prone position trials.DesignProspective, nonrandomized interventional study.SettingMedical intensive care unit, university tertiary care center.PatientsNineteen consecutive, mechanically ventilated patients (age 45 +/- 20 yrs, mean +/- SD) with ARDS and severe hypoxemia, defined as PaO2/FIO2of <or=to150 with FIO2or=to24 hrs, and a pulmonary artery occlusion pressure of <18 mm Hg.InterventionsPatients were turned prone for 2 hrs. Nonresponders were returned supine, but responders were maintained prone for 12 hrs before being returned to the supine position. The procedure was repeated on a daily basis in all patients, until inclusion criteria were no longer met or the patients died.Measurements and Main ResultsHemodynamic, blood gas, and gas exchange measurements were performed at the following time points: a) baseline supine; b) after 30 mins prone; and c) after 120 mins prone. Additional measurements for nonresponders were taken after 30 mins supine. For responders, additional measurements were taken after 12 hrs prone and 30 mins supine. Patients were considered responders if an increase in PaO2or=to1.3 kPa), or increase in the PaO2/FIO2or=to20 occurred within 120 mins. Eleven (57%) patients responded to the prone position. There was no difference in initial baseline parameters between responders and nonresponders. After 30 mins, the prone position in responders increased PaO2and decreased calculated venous admixture (Qva/Qt). This improvement was the maximal obtained, and was maintained throughout the 12-hr prone period. After 12 hrs prone, mean FIO2had been lowered from 0.85 +/- 0.16 to 0.66 +/- 0.18 (p < .05). Thirty minutes after the patients were returned supine, PaO2, PaO (2/FIO)2, and Qva/Qt were not different from 12-hr prone values, and were improved in comparison with baseline supine values. There was no worsening of gas exchange or hemodynamics in nonresponders. After the initial trial, a total of 28 additional episodes of prone position ventilation were performed in nine of the 19 patients. Of the 24 additional episodes in the responders, there was a response in 17 (71%) of 24 episodes. In the four additional episodes in nonresponders, there was a response in only one (25%) of four episodes. Response was accompanied by the same beneficial effects on gas exchange and Qva/Qt and absence of effect on hemodynamics as in the initial trial. There was no worsening in gas exchange or hemodynamics in nonresponder trials.ConclusionsBased on the data from this study, the prone position can improve oxygenation in severely hypoxemic ARDS patients without deleterious effects on hemodynamics. This beneficial effect does not immediately disappear on return to the supine position. In our patients, an absence of response to this technique was not accompanied by worsening hypoxemia or hemodynamic instability. Repeated daily trials in the prone position should be considered in the management of ARDS patients with severe hypoxemia. (Crit Care Med 1998; 26:1977-1985)

ISSN:0090-3493    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo monitor cardiac troponin I (cTnI), a newly developed biochemical index for cardiac damage, in patients during and after coronary artery bypass surgery (CABS) to determine whether the measurement of the serum levels of this marker could be of value in formulating an early diagnosis of Q-wave perioperative myocardial infarction (PMI).DesignProspective study with sequential measurements of biological markers in a selected surgical patient group.SettingUniversity research laboratory and general university hospital (Cardiac Surgery Unit and Anesthesiology and Reanimation Unit).PatientsForty-two patients undergoing elective CABS without concomitant valvular replacement.InterventionsThere were no interventions required for this study. However, patients entered into the study had CABS, sequential arterial blood samples, ECG recordings, and echocardiograms performed.Measurements and Main Results9.2 ng/mL), whereas the 34 nonPMI patients had peak values <9.0 ng/mL; therefore, sensitivity and specificity (with a 9.0 ng/mL cut-off value) are 100%. MB-CK measurement peak values did not demonstrate such a high specificity and sensitivity.ConclusionsBecause of its high specificity and sensitivity, serial measurements of cTnI provide a rapid and accurate method for confirming or excluding the diagnosis of perioperative myocardial injury. cTnI evaluation can therefore be used both as an independent prognostic marker for patients undergoing cardiac surgery and as a powerful tool for detecting smaller PMIs often missed with standard PMI diagnostic criteria. (Crit Care Med 1998; 26:1986-1990)

ISSN:0090-3493    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo compare the influence of gastric and postpyloric enteral feeding on the gastric tonometric PCO2gap (tonometric PCO2- PaCO2).DesignA prospective, clinical trial.SettingTwo intensive care units in a university hospital.PatientsTwenty patients undergoing mechanical ventilation and enteral feeding without catecholamines, sepsis, or sign of hypoxia.InterventionsPatients were randomized to receive feeding through the tonometer (gastric group), or through a postpyloric tube (postpyloric group).Measurements and Main ResultsThe patients received tube feeding at a rate of 50 mL/hr during 4 hrs. Baseline measurements included: mean arterial pressure, heart rate, tonometric parameters, arterial gases, and arterial lactate concentration. Except for lactate concentration, these measurements were repeated after 1 and 4 hrs of enteral feeding and 2 hrs after stopping enteral feeding. During the study, arterial pH and PaCO2did not change. During enteral feeding, the PCO2gap increased in the gastric group from a mean of 7 +/- 5 to 17 +/- 14 (SD) torr (0.9 +/- 0.7 to 2.3 +/- 1.9 kPa) (p < .01) and did not change in the postpyloric group (5 +/- 5 to 3 +/- 1 torr [0.7 +/- 0.7 to 0.4 +/- 0.1 kPa]). Two hours after stopping enteral feeding, the PCO2gap was still increased in the gastric group (15 +/- 9 vs. 7 +/- 5 torr [2.0 +/- 1.2 vs. 0.9 +/- 0.7 kPa]) (p < .01).ConclusionThe results indicate that gastric enteral feeding increased the PCO2gap. However, postpyloric enteral feeding does not interact with gastric tonometric measurements and should be used when using gastric tonometry in enterally fed patients. (Crit Care Med 1998; 26:1991-1994)

ISSN:0090-3493    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo compare two forms of continuous renal replacement therapy, continuous venovenous hemofiltration (CVVH) vs. continuous venovenous hemodialysis (CVVHD), in terms of the removal of inflammatory mediators from the blood of patients with systemic inflammatory response syndrome and acute renal failure.DesignRandomized crossover, clinical study.SettingUniversity teaching hospital.PatientsThirteen patients with systemic inflammatory response syndrome and acute renal failure receiving continuous renal replacement therapy.InterventionPatients were randomized to receive either convective clearance using CVVH or diffusive clearance using CVVHD for the first 24 hrs, followed by the other modality for 24 hrs. All treatments utilized AN69 hemofilters. CVVH was performed with an ultrafiltration rate of 2 L/hr and CVVHD with a dialysis outflow rate of 2 L/hr.Measurements and Main ResultsPlasma and ultrafiltrate concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and sL-selectin were measured at 0, 1, 3, 6, 12, and 24 hrs by radioimmunoassay. Plasma endotoxin concentrations were also measured at 0, 12, and 24 hrs by chromogenic assay. CVVH was associated with a 13% decrease in plasma TNF-alpha concentrations compared with a 23% increase while on CVVHD (p < .05). Mean plasma concentrations of IL-6, IL-10, and sL-selectin were unchanged over time and between therapies. Only minimal amounts of mediators were recovered in the effluents with either therapy except for IL-6. The clearances for IL-6 were different between therapies, 1.9 +/- 0.8 (SD) mL/min for CVVHD and 3.3 +/- 1.5 mL/min for CVVH, (p < .01). Plasma endotoxin concentrations were not different between therapies.ConclusionCVVH resulted in a decrease in plasma TNF-alpha concentrations as compared with CVVHD, while the type of transport mechanism used did not influence plasma concentrations of IL-6, IL-10, soluble L-selectin, or endotoxin. Differences in clearance for IL-6 between CVVH and CVVHD did not translate into significant changes in circulating IL-6 concentrations. (Crit Care Med 1998; 26:1995-2000)

ISSN:0090-3493    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveThe incidence of colonization and infection with vancomycin-resistant enterococci (VRE) has increased dramatically in the last 5 yrs, especially in intensive care units (ICUs). We studied VRE-colonization in patients on admission to a medical ICU (MICU) where VRE colonization is endemic.DesignProspective, descriptive analysis.SettingAn MICU of a public hospital.PatientsThree hundred and one consecutively admitted patients.Measurements and Main ResultsRectal swabs were obtained on admission from all patients. VRE isolates from all colonized patients were genetically fingerprinted by pulsed-field gel-electrophoresis (PFGE).Forty-three (14%) of 301 patients were colonized with VRE on MICU admission. Three (7%) of these 43 patients were admitted directly from the community without prior hospital contact. Risk of colonization on admission was related to the length of stay in the hospital before MICU-admission (odds ratio 4.65 for patients with a stay of at least 3 days) and previous in-hospital use of antibiotics. Of 22 VRE PFGE strain types recognized in the MICU during the study period, four (18%) were introduced by patients admitted directly from the community and ten (45%) were introduced by patients admitted from other hospital wards.ConclusionsThese results show that although ICUs are considered epicenters for antibiotic resistance, sources extraneous to our MICU (e.g., other wards) contributed the majority of VRE strain types in the unit. (Crit Care Med 1998; 26:2001-2004)

ISSN:0090-3493    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectivesTo obtain systematic information on the extrinsic coagulation pathway, as well as to investigate the time course of the coagulation abnormalities in sepsis.DesignProspective observational study.SettingGeneral intensive care unit.PatientsNineteen patients with the diagnosis of severe sepsis or septic shock and nine control patients.InterventionsNone.Measurements and Main ResultsTissue factor antigen concentration (tissue factor antigen), prothrombin fragment F1+2, thrombin antithrombin III complex, fibrinopeptide A, D-dimer, and antithrombin III concentrations were measured on the day of diagnosis of severe sepsis and septic shock, and on days 1, 2, 3, and 4 after diagnosis. The concentrations of tissue factor antigen, prothrombin fragment F1+2, fibrinopeptide A, and D-dimer were significantly increased in patients with severe sepsis and septic shock compared with control subjects. However, the concentrations of thrombin antithrombin III complex showed no statistical differences between the septic patients and the control subjects. Significantly, low antithrombin III concentrations were observed in the septic patient groups compared with control subjects. With the exception of D-dimer, the concentrations of the hemostatic markers were similar between severe sepsis and septic shock patients. Significant correlations were noted between tissue factor antigen and the disseminated intravascular coagulation score (r2= .236, p < .0001) and the number of dysfunctioning organs (r2= .229, p = .035).ConclusionsWe systematically elucidated coagulation disorders in newly defined sepsis. The extrinsic coagulation pathway is activated in patients with severe sepsis and septic shock. In these patients, enhanced thrombin generation and activation, and fibrin formation were demonstrated when compared with the control subjects. Furthermore, the thrombin generated appears not to be fully neutralized by antithrombin III. (Crit Care Med 1998; 26:2005-2009)

ISSN:0090-3493    

出版商:OVID    

年代:1998

数据来源: OVID