ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo evaluate the safety and efficacy of liposomal prostaglandin E1(TLC C-53) in the treatment of patients with the acute respiratory distress syndrome (ARDS).DesignRandomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial.SettingEight community and university-affiliated hospitals in the United States.PatientsTwenty-five patients with ARDS.InterventionsPatients were prospectively randomized in an unbalanced ratio within each site to receive either TLC C-53 (n equals 17) or placebo (n equals 8). Study drug was infused intravenously over 60 mins every 6 hrs for a 7-day period, starting at a dose of 0.15 micro gram/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 micro gram/kg/hr) was attained, intolerance to further increases developed, or invasive monitoring was discontinued. Patients received standard, aggressive, medical/surgical care throughout the trial.Measurements and Main ResultsOutcome measurements were PaO2/FIO2, dynamic pulmonary compliance, ventilator dependence on day 8, and 28-day all-cause mortality rate. At baseline, the distribution of variables describing Lung Injury Scores, Acute Physiology and Chronic Health Evaluation II scores, PaO2/FIO2, pulmonary compliance, and time from onset of ARDS to first dose of study drug was similar between patients in the TLC C-53 and placebo treatment groups. On day 8, all eight patients given placebo required mechanical ventilation, while eight of 17 patients given TLC C-53 were healthy enough to be removed from the ventilator (p equals .03). Improvement in PaO2/FIO2during the initial 8-day study period was greater in patients receiving TLC C-53. This trend achieved statistical significance on day 3, when the increase in PaO2/FIO2from baseline was 82.5 plus minus 14.6 in the TLC C-53 group compared with 28.3 plus minus 22.1 in the placebo group (p equals .05). By day 8, lung compliance also increased from baseline significantly more in TLC C-53 patients than in placebo patients (5.7 plus minus 1.7 vs. minus 1.5 plus minus 1.8 mL/cm H2O; p equals .01). The 28-day mortality rate was 6% (1/17 patients) in the TLC C-53 group and 25% (2/8 patients) in the placebo group (p equals .23). Drug-related adverse events were reported in 82% of the patients receiving TLC C-53 compared with 38% of the placebo group, with half of the adverse events in the TLC C-53 group being localized infusion site irritation. TLC C-53 was hemodynamically well tolerated, with transient hypotension occurring in three patients.ConclusionIn patients with ARDS, TLC C-53 was associated with improved oxygenation, increased lung compliance, and decreased ventilator dependency.(Crit Care Med 1996; 24:10-15)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveLiquid ventilation with perfluorocarbon previously has not been reported in pediatric patients with respiratory failure beyond the neonatal period. We evaluated the technique of partial liquid ventilation in six pediatric patients with the acute respiratory distress syndrome of sufficient severity to require extracorporeal life support (ECLS).DesignThis study was a noncontrolled, phase I/II experimental study with a single group pretest/posttest design.SettingAll studies were performed at a tertiary, pediatric referral hospital at the University of Michigan Medical School.PatientsSix pediatric patients, from 8 wks to 5 1/2 yrs of age, with severe respiratory failure requiring ECLS to support gas exchange.InterventionsAfter 2 to 9 days on ECLS, perfluorocarbon was administered into the trachea until the dependent zone of each lung was filled. The initial dose administered was 12.9 plus minus 2.3 mL/kg (range 5 to 20). Gas ventilation of the perfluorocarbon-filled lungs (partial liquid ventilation) was then performed. The perfluorocarbon dose was repeated daily for a total of 3 to 7 days, with a cumulative dose of 45.2 plus minus 6.1 mL/kg (range 30 to 72.5).Measurements and Main ResultsAll measurements of native gas exchange were made during brief periods of discontinuation of ECLS and include PaO2and the alveolar-arterial oxygen gradient, P(A-a)O2. Static pulmonary compliance, corrected for weight, was also measured directly.The mean PaO sub 2 increased from 39 plus minus 6 to 92 plus minus 29 torr (5.2 plus minus 0.8 to 12.2 plus minus 3.9 kPa) over the 96 hrs after the initial dose (p equals .021 by repeated-measures analysis of variance). The average P(A-a)O sub 2 decreased from 635 plus minus 10 to 499 plus minus 77 torr (84.7 plus minus 1.3 to 66.5 plus minus 10.3 kPa) over the same time period (p equals .059), while the mean static pulmonary compliance (normalized for patient weight) increased from 0.12 plus minus 0.02 to 0.28 plus minus 0.08 mL/cm H2O/kg (p equals .01). All six patients survived. Complications potentially associated with partial liquid ventilation were limited to pneumothoraces in two of six patients.ConclusionsPerfluorocarbon may be safely administered into the lungs of pediatric patients with severe respiratory failure on ECLS and may be associated with improvement in gas exchange and pulmonary compliance.(Crit Care Med 1996; 24:16-22)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesTo compare data derived from a computer model of the pulmonary circulation with data from a case series of patients with chronic obstructive pulmonary disease (COPD). To evaluate the specific factors contributing to CO2retention due to oxygen therapy in patients with acute exacerbations of COPD.DesignData from a computer model of the pulmonary circulation were compared with a previous case series.PatientsPatient data were derived from previous case series.InterventionsSimulated application of oxygen therapy.Measurements and Main ResultsThe computer model of the pulmonary circulation generates data comparable with those data from a series of patients with COPD treated with supplemental oxygen and permits identification of the causes for hypercarbia. Therapy with supplemental oxygen alters hypoxic pulmonary vasoconstriction and modulates the Haldane effect, resulting in changes in physiologic deadspace.ConclusionChanges in physiologic deadspace are sufficient to account for the hypercarbia developed by patients with acute exacerbations of COPD when treated with supplemental oxygen.(Crit Care Med 1996; 24:23-28)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesTo quantify oxyradical inflammatory markers in serial endotracheal tube aspirates obtained from premature neonates at risk for developing bronchopulmonary dysplasia, and to correlate these parameters with clinical manifestations of the disease.DesignProspective cohort study.SettingTertiary neonatal intensive care unit.PatientsTwenty-eight intubated, premature infants, with 15 infants displaying simple respiratory distress syndrome and 13 infants eventually developing bronchopulmonary dysplasia.InterventionsEndotracheal tube aspirates were collected and clinical severity scores were calculated longitudinally from an inception cohort during the first week of life. Diagnosis of bronchopulmonary dysplasia by standard criteria was recorded at 30 days of life. Various biochemical analyses related to pulmonary oxyradical stress were determined on endotracheal tube aspirates and were normalized according to the magnitude of serum/aspirate urea ratios. The demographic, illness severity, and biochemical characteristics of infants with simple respiratory distress syndrome and those characteristics of infants developing bronchopulmonary dysplasia were evaluated by masked comparison.Measurements and Main ResultsPopulations of respiratory distress syndrome and bronchopulmonary dysplasia infants could be differentiated during the first week of life by means of the following parameters: gestational age; birth weight; Score of Neonatal Acute Physiology; Neonatal Therapeutic Intervention Scoring System; epithelial lining fluid leukocytes; elastase; myeloperoxidase; xanthine oxidase and catalase enzyme activities; and total sulfhydryls.ConclusionsInfants with simple respiratory distress syndrome could be segregated from those infants who developed bronchopulmonary dysplasia by the magnitude of the epithelial lining fluid oxyradical inflammation markers. While infants developing bronchopulmonary dysplasia typically exhibited increased concentrations of these markers during the first week of life, those infants with simple respiratory distress syndrome displayed low, uniform, or decreasing values of these markers over this interval. Infants developing bronchopulmonary dysplasia demonstrate an early pulmonary inflammatory response, and one key aspect of this response involves various oxyradical-generating systems.(Crit Care Med 1996; 24:29-37)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesThe aims of this study were to evaluate the safety and efficacy of magnesium replacement therapy and to determine its effect on potassium retention in hypokalemic, critically ill patients.DesignA prospective, double-blind, randomized, placebo-controlled trial.SettingA surgical intensive care unit (ICU).PatientsA total of 32 adult surgical ICU patients were admitted to the study on the basis of documented hypokalemia (potassium of less than 3.5 mmol/L) within the 24-hr period before entering the study. Patients were randomized to receive either placebo (n equals 15) or magnesium sulfate (n equals 17). One patient from each group was excluded from the study due to failure to complete the full series of doses.InterventionsPatients received a "test dose" of either magnesium sulfate (2 g, 8 mmol) or placebo (5% dextrose in water) infused over 30 mins every 6 hrs for eight doses. The next scheduled test dose was held if hypermagnesemia (magnesium of more than 2.8 mg/dL [more than 1.15 mmol/L]) was documented at any time during the study. Routine replacements of potassium and magnesium continued during the duration of the study, when clinically indicated, for serum potassium concentrations of 3.5 mmol/L or serum magnesium concentrations of less than 1.8 mg/dL (less than 0.74 mmol/L).Measurements and Main ResultsAge, weight, and Acute Physiology and Chronic Health Evaluation II scores were recorded on entry into the study. Just before administration of each test dose, blood was drawn for magnesium and potassium, bicarbonate, pH, and glucose determinations, and an aliquot of the preceding 6 hrs urine collection was sent for magnesium and potassium determinations. Serum calcium, phosphate, urea nitrogen, and creatinine concentrations were measured daily. The amounts of magnesium and potassium administered via parenteral nutrition, tube feeding, and replacement infusions were calculated for each 6-hr interval. The amounts of magnesium and potassium excreted in the urine were similarly assessed.The groups showed no differences with regard to age, weight, Acute Physiology and Chronic Health Evaluation II scores, or initial serum magnesium concentration.Initial potassium, bicarbonate, pH, calcium, phosphate, glucose, blood urea nitrogen, and creatinine values were not different between groups. Patients receiving magnesium sulfate showed a statistically significant increase in serum magnesium concentration at 6 hrs when compared with placebo, as well as with itself at time 0 (p less than .0001), a difference maintained throughout the study. Compared with the placebo group, the total amount of elemental magnesium administered was significantly greater in the treatment group (1603 plus minus 124 vs. 752 plus minus 215 mg [65.7 plus minus 5.8 vs. 30.8 plus minus 8.8 mmol], p less than .0001), as was urine magnesium excretion (1000 plus minus 156 vs. 541 plus minus 68 mg [41.0 plus minus 6.4 vs. 22.2 plus minus 2.8 mmol] p less than .0001). However, the net magnesium balance (total magnesium in - total urine magnesium) was signficantly more positive in the treatment group (612 plus minus 180 vs. 216 plus minus 217 mg [25.1 plus minus 7.4 vs. 8.9 plus minus 8.9 mmol], p less than .005). The treatment and control groups had the same serum potassium concentrations and did not receive different amounts of potassium (245 plus minus 39 vs. 344 plus minus 45 mmol, respectively, p equals .06), although the treatment group required less potassium replacement/6 hrs by 30 hrs compared with itself at time 0 (p less than .05). Despite the same serum potassium values, the net potassium balance for 48 hrs was positive in the treatment group (plus 72 plus minus 32 mmol) and negative in the control group (minus 74 plus minus 95 mmol, p less than .05). There were no complications associated with the magnesium sulfate administration.ConclusionsMagnesium sulfate administered according to the above regimen safely and significantly increases the circulating magnesium concentration. Despite greater urine magnesium losses in the treatment group, this group exhibited significantly better magnesium retention. In addition, within 30 hrs of entry into the study, the treatment group exhibited a net positive and statistically significant (p less than .05) improvement in potassium balance compared with the control group.(Crit Care Med 1996; 24:38-45)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesTo investigate a novel anticytokine therapy in patients with sepsis syndrome, and the relationship between a patient's baseline mortality risk and survival benefit.DesignData from a recent phase III, double-blind, placebocontrolled, multicenter clinical trial with patients randomized to three treatment arms: an intravenous loading dose of recombinant human interleukin-1-receptor antagonist (rhIL-1ra) or placebo, followed by a continuous infusion of rhIL-1ra (1.0 mg/kg/hr, or 2.0 mg/kg/hr), or placebo for 72 hrs.SettingSixty-three investigative centers in eight countries.PatientsThe study population consisted of 893 patients: 302 placebo patients; 298 patients treated with 1.0 mg/kg/hr of rhIL-1ra; and 293 patients treated with 2.0 mg/kg/hr of rhIL-1ra.Measurements and Main ResultsAn independent, sepsis-specific, log-normal regression model that predicts the risk of mortality over 28 days was applied to all patients enrolled into the rhIL-1ra sepsis study. The ability of the Predicted Risk of Mortality model to predict 28-day mortality in the placebo patients was determined and the relationship between mortality risk and efficacy of rhIL-1ra was investigated. The trial data were also analyzed using two other risk-assessment models for comparison with Predicted Risk of Mortality.A significant increase in survival time was demonstrated for all patients treated with rhIL-1ra (n equals 893, p less than .02 Predicted Risk of Mortality log-normal), but patients with a Predicted Risk of Mortality of less than 24% derived little benefit. Retrospective examination of time-to-death data demonstrated that rhIL-1ra reduced risk of death in the first 2 days for patients with more than equals 24% Predicted Risk of Mortality (n equals 580, p less than .005 Predicted Risk of Mortality log-normal). This same effect was not present in patients with a Predicted Risk of Mortality of less than 24% on entry into the study. The Predicted Risk of Mortality model predicted a 28-day mortality rate of 35% for placebo patients compared with 34% observed and accurately stratified patients along the full range of risks. There was a wide distribution of individual patient risks for 28-day mortality for all patients, as well as within categorical subgroups, such as shock and organ system dysfunction. Two alternate risk models were assessed and the Acute Physiology Score of Acute Physiology and Chronic Health Evaluation III also demonstrated a statistically significant survival benefit for rhIL-1ra (p equals .04 Predicted Risk of Mortality log-normal) for all patients treated.ConclusionsUsing an appropriate analytic model, a statistically significant increase in survival time from rhIL-1ra was measured. A direct relationship was found between a patient's Predicted Risk of Mortality at study entry to efficacy of rhIL-1ra. Individual risk or severity assessment may be a useful tool for evaluating the clinical benefit of new therapeutic approaches to sepsis and for monitoring outcomes at the bedside.(Crit Care Med 1996; 24:46-56)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID