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 investigate the safety, biological effects, and efficacy of the anti-tumor necrosis factor (TNF) antibody fragment, MAK 195F, in a phase II trial in patients with severe sepsis.DesignProspective, randomized, open label, placebo-controlled, dose-ranging, multicenter, multinational clinical trial.SettingSixteen academic medical centers' intensive care units in six European countries.PatientsOne hundred twenty-two patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy.InterventionsPatients received one of three different doses of the anti-TNF antibody (0.1 mg/kg, 0.3 mg/kg, or 1.0 mg/kg) or placebo; the antibody or placebo was given in nine doses at 8-hr intervals over 3 days.Measurements and Main ResultsThere were no significant differences in mortality rates among the groups receiving various doses of the anti-TNF antibody or placebo, but patients with baseline serum interleukin (IL)-6 concentrations of more than 1000 pg/mL appeared to benefit from MAK 195F in a dose-dependent fashion. Increased circulating IL-6 concentrations, but not TNF concentrations, were found to be important prognostic indicators for mortality for the patients in the placebo and the two lower dosage groups but not in the high dosage group (1 mg/kg). IL-6 concentrations decreased during the first 24 hrs of treatment in all three anti-TNF groups but not in the placebo group. MAK 195F was well tolerated by all patients. Human antimurine antibodies developed in 40% of the patients receiving the antibody.ConclusionsThere was no increase in survival from sepsis for the patients receiving anti-TNF treatment in the overall study population. Retrospective stratification of patients by IL-6 concentrations suggests beneficial effects of the drug for patients with baseline circulating IL-6 concentrations of more than 1000 pg/mL. This hypothesis requires validation in a larger, blinded, prospective study.(Crit Care Med 1996; 24:733-742)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesThe relationship between physiologic status and mortality risk should be reevaluated as new treatment protocols, therapeutic interventions, and monitoring strategies are introduced, and as patient populations change. We developed and validated a third-generation pediatric physiology-based score for mortality risk, Pediatric Risk of Mortality III (PRISM III).DesignProspective cohort.SettingThere were 32 pediatric intensive care units (ICUs): 16 pediatric ICUs were randomly chosen and 16 volunteered.PatientsConsecutive admissions at each site were included until at least 11 deaths per site occurred.Measurements and Main ResultsPhysiologic data included the most abnormal values from the first 12 and the second 12 hrs of ICU stay. Outcomes and descriptive data were also collected. Physiologic variables where normal values change with age were stratified by age (neonate, infant, child, adolescent). The database was randomly split into development (90%) and validation (10%) sets. Variables and their ranges were chosen by computing the risk of death (odds ratios) relative to the midrange of survivors for each physiologic variable. Univariate and multivariate statistical procedures, including multiple logistic regression analysis, were used to develop the PRISM III score and mortality risk predictors.Data were collected on 11,165 admissions (543 deaths). The PRISM III score has 17 physiologic variables subdivided into 26 ranges. The variables most predictive of mortality were minimum systolic blood pressure, abnormal pupillary reflexes, and stupor/coma. Other risk factors, including two acute and two chronic diagnoses, and four additional risk factors, were used in the final predictors. The PRISM III score and the additional risk factors were applied to the first 12 hrs of stay (PRISM III-12) and the first 24 hrs of stay (PRISM III-24). The Hosmer-Lemeshow chi-square goodness-of-fit evaluations demonstrated absence of significant calibration errors (p values: PRISM III-12 development equals .2496; PRISM III-24 development equals .1374; PRISM III-12 validation equals .4168; PRISM III-24 validation equals .5504). The area under the receiver operating curve and Flora's z-statistic indicated excellent discrimination and accuracy (area under the receiver operating curve--PRISM III-12 development 947 plus minus 0.007; PRISM III-24 development 0.958 plus minus 0.006; PRISM III-12 validation 0.941 plus minus 0.021; PRISM III-24 validation 0.944 plus minus 0.021; Flora's z-statistic--PRISM III-12 validation equals .7479; PRISM III-24 validation equals .9225), although generally, the PRISM III-24 performed better than the PRISM III-12 models. Excellent goodness-of-fit was also found for patient groups stratified by age (significance levels: PRISM III-12 equals .1622; PRISM III-24 equals .4137), and by diagnosis (significance levels: PRISM III-12 equals .5992; PRISM III-24 equals .7939).ConclusionsPRISM III resulted in several improvements over the original PRISM. Reassessment of physiologic variables and their ranges, better age adjustment for selected variables, and additional risk factors resulted in a mortality risk model that is more accurate and discriminates better. The large number of diverse ICUs in the database indicates PRISM III is more likely to be representative of United States units.(Crit Care Med 1996; 24:743-752)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo investigate the relationship between baseline risk of death and reduced mortality after selective decontamination of the digestive tract in intensive care unit patients.DesignAnalysis of data from a meta-analysis of 23 randomized, controlled trials.PatientsA total of 4,142 adult intensive care unit patients from the 23 trials.Measurements and Main ResultsMortality for patients receiving selective decontamination of the digestive tract treatment was analyzed as a function of baseline risk of death at study entry, using weighted least squares regression across all 23 trials. In testing whether the slope of the regression is different than 1.0, the observed t value is 3.32 (p less than .004), suggesting that the efficacy of selective decontamination of the digestive tract in reducing mortality is significantly better in populations at high mortality risk at study entry.ConclusionsMortality reduction from selective decontamination of the digestive tract appears related to the mortality risk of patients at the time of study entry. Future trials should consider using baseline risk assessment as part of trial design and outcome analysis.(Crit Care Med 1996; 24:753-755)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo evaluate the physiology and pharmacokinetics of a novel hemoglobin-based oxygen carrier of bovine origin.DesignRandomized, single-blind, placebo-controlled, doseescalation study.SettingThe Upjohn Research Clinics (Kalamazoo, MI).SubjectsNormal healthy adult men between the ages of 18 and 45 yrs. There were 18 subjects who received active treatment and 23 controls.InterventionsAll subjects had phlebotomy of 15% of blood volume (performed in less than 15 mins) followed by isovolemic hemodilution (3:1, Ringer's lactate to the volume of whole blood removed) over a 90-min period, and either active drug (polymerized bovine hemoglobin) or a control infusion of lactated Ringer's solution (each infusion given over a total of 4.3 hrs). The subjects randomized to active treatment received a loading dose and a continuous infusion of polymerized bovine hemoglobin for a total dose of 16.5, 24.1, 30.2, 38.0, or 45.0 g. All subjects had an indwelling radial artery catheter (for blood pressure and arterial blood gas measurements), determination of cardiac function (by impedance plethysmography), serial pulmonary function tests (spirometry and diffusion capacity), and metabolic cart measurements.Measurements and Main ResultsPharmacokinetics of the plasma bovine hemoglobin demonstrated that the elimination of the hemoglobin-based oxygen carrier was a linear, first-order process and that there was no renal excretion. Peak plasma concentrations were between 1 to 2 g/dL and plasma half-life approached 20 hrs at the highest doses given. Diffusion capacity of oxygen was increased up to 20% above baseline in the 38.0 and 45.0 g groups in comparison with controls (approximate 14% below baseline) between 2 and 24 hrs after the infusion (p less than .01). Other pulmonary function tests and arterial blood gas measurements were unremarkable. Arterial oxygen content and oxygen delivery tended to be greater in active groups than in controls.ConclusionsThe plasma concentrations of bovine hemoglobin were directly proportional to the doses administered. An increase in diffusion capacity paralleled the plasma bovine hemoglobin concentrations. Dosing of the hemoglobin-based oxygen carrier of bovine origin to a target plasma hemoglobin concentration can be achieved using pharmacokinetic principles with measurable effects on oxygen physiology.(Crit Care Med 1996; 24:756-764)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesTo describe the postoperative course of patients who underwent hyperthermic isolated limb perfusion with recombinant tumor necrosis factor (TNF)-alpha and melphalan after pretreatment with recombinant interferon-gamma as treatment for recurrent melanoma, primary nonresectable soft-tissue tumors, planocellular carcinoma, or metastatic carcinoma. To measure systemic TNF-alpha concentrations and relate these values with indices of disease severity.SettingA 12-bed surgical intensive care unit (ICU) in a university referral hospital.DesignProspective, descriptive study.PatientsConsecutive patients (n equals 25) treated with hyperthermic isolated limb perfusion.InterventionsBlood samples were taken at regular intervals to determine TNF-alpha concentrations during and after hyperthermic isolated limb perfusion with recombinant TNF-alpha. Hemodynamic variables were obtained with a Swan-Ganz pulmonary artery catheter.Measurements and Main ResultsAll patients developed features of sepsis syndrome and required intensive care treatment. Most patients recovered quickly, with a median ICU stay of 2 days (range 1 to 25). Maximum systemic TNF-alpha concentrations ranged from 2284 to 83,000 ng/L (median 25,409) and returned to baseline values within 8 hrs. Despite these high concentrations of TNF-alpha, no patient died in the ICU, although the patient with the highest TNF-alpha concentration developed multiple organ failure and required continuous venovenous hemofiltration for 16 days.Linear regression analysis showed positive correlations between maximum TNF-alpha concentrations and systemic vascular resistance (p less than .01), cardiac index (p less than .02), Lung Injury Score (p less than .02), prothrombin time (p less than .02), and activated partial thromboplastin time (p less than .05).ConclusionsHyperthermic isolated limb perfusion with recombinant TNF-alpha leads to high systemic concentrations of TNF-alpha, probably due to leakage of recombinant TNF-alpha from the perfusion circuit, mainly through collateral blood flow. A sepsis-like syndrome is seen in all patients. Despite high concentrations of systemic TNF-alpha, this sepsis syndrome is short-lived and recovery is rapid and complete in most patients.(Crit Care Med 1996; 24:765-770)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveAirway occlusion pressure at 0.1 sec (P0.1) is an index of respiratory center output. During pressure-support ventilation, P0.1 correlates with the mechanical output of the inspiratory muscles and has an inverse relationship with the amount of pressure-support ventilation. Based on these observations, we designed a closed-loop control which, by automatically adjusting pressure-support ventilation, stabilizes P0.1, and hence patient inspiratory activity, at a desired target. The purpose of the study was to demonstrate the feasibility of the method, rather than its efficacy or even its influence on patient outcome.DesignProspective, randomized trial.SettingA general intensive care unit of a university hospital in Italy.PatientsEight stable patients intubated and ventilated with pressure-support ventilation for acute respiratory failure.InterventionsPatients were transiently connected to a computer-controlled ventilator on which the algorithm for closed-loop control was implemented. The closed-loop control was based on breath by breath measurement of P0.1 and on comparison with a target set by the user. When actual P0.1 proved to be higher than the target value, the P0.1 controller automatically increased pressure-support ventilation, and decreased it when P0.1 proved to be lower than the target value. For safety, a volume controller was also implemented. Four P0.1 targets (1.5, 2.5, 3.5, and 4.5 cm H2O) were applied at random for 15 mins each.Measurements and Main ResultsThe closed-loop algorithm was able to control P0.1, with a difference from the set targets of 0.59 plus minus 0.27 (SD) cm H2O.ConclusionsThe study shows that P0.1 can be automatically controlled by pressure-support ventilation adjustments with a computer. Inspiratory activity can thus be stabilized at a level prescribed by the physician.(Crit Care Med 1996; 24:771-779)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo study comparatively the effects of volume-controlled vs. biphasic positive airway pressure mechanical ventilation on respiratory mechanics and oxygenation in leukopenic patients with severe respiratory failure.DesignProspective, comparative study.SettingMedical intensive care unit of a university hospital.PatientsLeukopenic (less than 1000 leukocytes/micro Liter) patients (n equals 20) after cytoreductive chemotherapy requiring mechanical ventilation for severe respiratory failure (Murray score of more than 2.5).InterventionPatients were assigned in a consecutive, alternating manner to receive either volume-controlled or biphasic positive airway pressure mechanical ventilation, starting within 12 to 24 hrs after endotracheal intubation.Measurements and Main ResultsTidal volume, inspiratory flow, peak inspiratory and positive end-expiratory pressures, FIO2, and arterial blood gas analyses were recorded hourly for a study period of 48 hrs. Biphasic positive airway pressure ventilation was associated with a significant reduction in peak inspiratory pressure (mean differences at 24, 36, and 48 hrs: 4.4, 3.4, and 4.2 cm H2O; p equals .024,.019, and .013, respectively) and positive end-expiratory pressures (mean differences at 24, 36, and 48 hrs: 1.6, 1.4, and 1.5 cm H2O; p equals .023,.024, and .023, respectively) at significantly lower FIO2(mean differences at 12, 24, 36, and 48 hrs; p equals .007,.015,.016, and .011, respectively). PaO2/FIO2ratios and CO2removal were similar under ventilatory conditions.ConclusionsBiphasic positive airway pressure ventilation offers the advantage of significantly reduced peak inspiratory and positive end-expiratory pressures at a lower FIO2and with at least similar oxygenation and CO2removal as achieved by volume-controlled mechanical ventilation. Our results are in line with previous reports on nonleukopenic patients and suggest that the positive effects of pressure-limited mechanical ventilation are independent of circulating white blood cells. Further studies are mandatory to demonstrate clinical benefit in this critically ill patient population.(Crit Care Med 1996; 24:780-784)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo examine the agreement and association of a noninvasive method of measuring CO2(using end-tidal PCO2) with PaCO2in mechanically ventilated adults with severe head trauma.DesignA prospective, quasi-experimental, repeated-measures study was used to compare end-tidal PCO2and PaCO2at two time points: before and after a standardized endotracheal suctioning procedure.InterventionsControlled intervention of endotracheal suctioning.SettingThe study was conducted at two intensive care units designated as Level 1 trauma centers.PatientsA consecutive sample of 35 severe head-injured patients with a Glasgow Coma Scale score of less than equals 8.Measurements and Main ResultsEnd-tidal PCO2and PaCO2values were simultaneously obtained and compared. End-tidal PCO2was measured, using a sidestream sensor placed in line of the ventilator circuit's deadspace. Arterial gases were drawn from an indwelling arterial catheter.No relationship was found between arterial and end-tidal measures (range r sup 2 equals .09 to r2equals .11). Using the Bland-Altman technique, agreement decreased as the amount of positive end-expiratory pressure increased. When a subset of patients (mechanically ventilated, with positive end-expiratory pressures of less than 5 cm H2O, paralyzed, and sedated) were examined (n equals 12), the correlation between the CO2measures improved (r2equals .77).ConclusionsThis study indicated that end-tidal PCO2monitoring correlates well with PaCO2in patients without respiratory complications or without spontaneous breathing, resulting in rebreathing of gases. However, its clinical validity is questionable in patients who have the greatest need for end-tidal PCO2monitoring (i.e., patients who have respiratory distress or who are breathing spontaneously and overriding the ventilator).(Crit Care Med 1996; 24:785-790)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID