摘要:

ObjectiveTo assess the cost-effectiveness of drotrecogin alfa (activated) therapy, which was recently shown to reduce mortality in severe sepsis.DesignEstimates of effectiveness and resource use were based on data collected prospectively as part of a multicenter international trial. Estimates of hospital costs were based on a subset of the patients treated in the United States (33% of all enrolled patients). Lifetime projections were modeled from published sources and tested in sensitivity analyses. Analyses were conducted from the United States societal perspective, limited to healthcare costs, and using a 3% annual discount rate.SettingA total of 164 medical institutions in 11 countries.PatientsAdults ≥18 yrs of age with severe sepsis.InterventionsEligible patients were randomly assigned to receive a 96-hr intravenous infusion of drotrecogin alfa (acti-vated) at 24 &mgr;g/kg/hr (n = 850) or placebo (n = 840).Measurements and Main ResultsBase Case: incremental short-term (days 1–28) healthcare costs per day-28 survivor; Panel on Cost-Effectiveness in Health and Medicine Reference Case: incremental lifetime healthcare costs per quality-adjusted life-year. Over the first 28 days (short-term Base Case), drotrecogin alfa (activated) increased the costs of care by $9,800 and survival by 0.061 lives saved per treated patient. Thus, drotrecogin alfa (activated) cost $160,000 per life saved (with 84.7% probability that ratio is <$250,000 per life saved). Projected to lifetime (lifetime Reference Case), drotrecogin alfa (activated) increased the costs of care by $16,000 and quality-adjusted survival by 0.33 quality-adjusted life-years per treated patient. Thus, drotrecogin alfa (activated) cost $48,800 per quality-adjusted life-year (with 82% probability that ratio is <$100,000 per quality-adjusted life-year). Estimates were generally robust to sensitivity analyses, although cost-effectiveness deteriorated to >$100,000 per quality-adjusted life-year if survivors lived <4.6 yrs on average. Drotrecogin alfa (activated) cost $27,400 per quality-adjusted life-year when limited to patients with an Acute Physiology and Chronic Health Evaluation II score ≥25 and was cost-ineffective when limited to patients with a score <25.ConclusionsDrotrecogin alfa has a cost-effectiveness profile similar to that of many well-accepted healthcare strategies and below commonly quoted thresholds.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo assess the effects of drotrecogin alfa (activated) therapy, a recombinant human activated protein C, across clinically relevant subpopulations in a randomized, phase 3, placebo-controlled study of patients with severe sepsis (recombinant human activated protein C worldwide evaluation in severe sepsis [PROWESS]).DesignUnivariate and multivariable analysis of prospectively defined subgroups from the PROWESS study.SettingA total of 164 medical centers in 11 countries.PatientsA total of 1,690 patients with severe sepsis.Measurements and Main ResultsWe report observed 28-day mortality rates for drotrecogin alfa (activated) and placebo patients for subgroups prospectively defined by demographic data, surgical status, type and site of infection, and clinical and biochemical measures of disease severity. We performed subgroup analyses to explore the consistency of the mortality benefit observed in the overall population and performed tests for both quantitative and qualitative interactions. To examine the magnitude of the treatment benefit with drotrecogin alfa (activated) across the underlying predicted risk of mortality spectrum, we used stepwise logistic regression on PROWESS placebo patients to generate a predicted risk of mortality model that simultaneously included many clinical and biochemical markers of mortality risk. Because drotrecogin alfa (activated) has anticoagulant properties, we also present analyses of bleeding and thrombotic events. Actual mortality rates were lower with drotrecogin alfa (activated) compared with placebo for nearly all prospectively defined subgroups. Both univariate and multivariable regression analyses showed a consistent relative risk reduction in 28-day mortality rates for drotrecogin alfa (activated). Larger absolute risk reductions were found with drotrecogin alfa (activated) in patients with a higher baseline predicted risk of mortality, and actual mortality rates were lower with drotrecogin alfa (activated) in all subgroups defined by disease severity measures where a ≥20% placebo mortality was observed. Although discriminatory power was limited by few observed events, the increased absolute risk of experiencing a serious bleeding event with treatment did not seem to vary according to the baseline predicted risk of mortality.ConclusionsThe administration of drotrecogin alfa (activated) to patients with severe sepsis was associated with a significant survival benefit that tended to increase with higher baseline likelihood of death. Current data suggest that the increased risk of bleeding does not vary according to likelihood of death.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveThe primary objective of this study was to test the hypothesis that in patients intubated for acute lung injury, lower concentrations of surfactant proteins A and D in the pulmonary edema fluid and higher concentrations in the plasma are associated with more severe lung injury and worse clinical outcomes.DesignObservational study.SettingIntensive care unit patients in a tertiary university hospital and a university-affiliated city hospital.PatientsThirty-eight intubated, mechanically ventilated intensive care unit patients with acute lung injury or acute respiratory distress syndrome as defined by the North American European Consensus Conference.InterventionsUndiluted pulmonary edema fluid and plasma samples were collected within 24 hrs of endotracheal intubation in all patients.Measurements and Main ResultsThe concentrations of surfactant proteins A and D were measured in pulmonary edema fluid and in plasma. Plasma surfactant protein A, but not surfactant protein D, was higher in patients with fewer days of unassisted ventilation (p= .03) and in patients with an absence of intact alveolar fluid clearance (p= .03). In contrast, pulmonary edema fluid surfactant protein D, but not surfactant protein A, was lower in patients with worse oxygenation, as measured by the alveolar-arterial oxygen difference (p= .01) and was lower in the patients who died (2646 ng/mL) compared with those who survived (5503 ng/mL;p= .02).ConclusionsThese results demonstrate that reduced pulmonary edema fluid surfactant protein D and elevated plasma surfactant protein A concentrations at the onset of acute lung injury may be associated with more severe disease and worse clinical outcome and may serve as valuable biochemical markers of prognosis.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesTo determine whether children who experience longer intensive care unit (ICU) stays after open heart surgery may be identified at admission by clinical criteria. To identify factors associated with longer ICU stays that are potential targets for quality improvement.SettingTertiary pediatric cardiac surgical center.DesignA retrospective review was performed of pre-, intra-, and postoperative factors for children undergoing open heart surgery. All factors were evaluated for strength of association with length of ICU stay (LOS) using a negative binomial model. After multiple analysis, factors were deemed significant if associated with a LOS withp< .02.PatientsA total of 355 pediatric patients who had cardiac surgery with cardiopulmonary bypass in a 1-yr period from April 1999 until March 2000.Measurements and Main ResultsChildren who fell above the 95th percentile for LOS in our institution occupied 30% of bed days and had a three-fold greater mortality. Of all clinical factors considered, those significantly associated with LOS were as follows:preoperative—mechanical ventilation, neonatal status, medical problems, and transfer from abroad;intraoperative—higher operative complexity, increased cardiopulmonary bypass time or ischemic time, and circulatory arrest; andpostoperative—delayed sternal closure, sepsis, renal failure, pulmonary hypertension, chylothorax, diaphragm paresis, and arrhythmia. A model combining all factors identified preoperative mechanical ventilation, neonatal status, major medical problems, operative complexity, cardiopulmonary bypass time, and a postoperative complication score as independently associated with LOS (p< .01).ConclusionsAt the time of ICU admission after open heart surgery, clinical criteria are evident that highlight a child’s risk of longer ICU stay. These pre- and intraoperative factors relate to LOS independent of subsequent postoperative events. Those postoperative complications that are most strongly associated with increased LOS are identified and, therefore, made accessible to quality control.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo determine the functionality of identified polymorphisms in the promoter and upstream regions of the interleukin-10 gene in terms of release of interleukin-10 from lipopolysaccharide-stimulated whole blood from healthy volunteers and to evaluate the relationship of interleukin-10 polymorphisms to interleukin-10 release, development of sepsis, and mortality in critically ill patients.DesignObservational study.SettingThe academic unit of anesthesia and intensive care, university laboratories, and ten-bed general intensive care unit in a university teaching hospital.SubjectsA total of 132 healthy volunteers plus 67 consecutive critically ill patients recruited within 24 hrs of admission to the intensive care unit, regardless of diagnosis.MeasurementsPlasma interleukin-10 levels were measured by enzyme-linked immunosorbent assay. Single nucleotide polymorphisms were detected by restriction fragment length polymorphism analysis. Dinucleotide repeat polymorphisms were identified after polymerase chain reaction using a DNA size analyzer.Main ResultsStimulated interleukin-10 release in critically ill patients was significantly lower than in healthy subjects (p< .0001). In addition, in the patients who developed sepsis, interleukin-10 release at admission to the intensive care unit was significantly lower than in patients who did not subsequently develop sepsis (median [range] 1.47 [0.13–6.90] ng/mL compared with 4.93 [0.03–16.80] ng/mL,p= .001). The A allele of the single nucleotide polymorphism at −592 base pairs was associated with lower interleukin-10 release and higher mortality in critically ill patients. Other polymorphisms were not linked to interleukin-10 release, sepsis, or mortality.ConclusionsThe A allele of the −592 base pair single nucleotide polymorphism in the interleukin-10 gene is associated with lower stimulated interleukin-10 release and increased mortality. Further investigations are required to determine the nature of the functionality and the potential diagnostic and therapeutic aspects of this marker.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo evaluate the efficacy of intravenous erythromycin as a method to facilitate feeding tube placement into the small intestine in critically ill patients.DesignDouble blind, randomized, controlled trial.SettingMedical and surgical intensive care units in an academic medical center.PatientsProspective cohort of 36 consecutive adults requiring intensive care unit care and enteral tube feeding for nutritional support.InterventionInfusion of a single dose of intravenous erythromycin (500 mg) or saline before placement of 10-Fr feeding tubes using a standardized active bedside protocol.Measurements and Main ResultsWe determined the success rate of feeding tube placement into or beyond the second portion of the duodenum and the time required for this procedure by experienced nurses. The feeding tube was considered to be postpyloric when the tip was in the second portion of the duodenum or beyond. The predictive value of a serial step-up in gastrointestinal aspirate pH from ≤5.0 to ≥6.0 was also determined. Use of intravenous erythromycin significantly improved the rate of feeding tube placement into the duodenum or jejunum (erythromycin group, 13 of 14 patients or 93% vs. the control group, 12 of 22 patients or 55%;p< .03). Erythromycin administration also significantly decreased the procedure time from 25 ± 3 to 15 ± 2 mins (p< .04). Feeding tube placement into either duodenum or jejunum was confirmed in all 18 patients with a pH step-up from ≤5.0 to ≥6.0.ConclusionA single bolus dose of intravenous erythromycin facilitates active bedside placement of postpyloric feeding tubes in critically ill adult patients.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveScoring systems that predict mortality do not necessarily predict prolonged length of stay or costs in the intensive care unit (ICU). Knowledge of characteristics predicting prolonged ICU stay would be helpful, particularly if some factors could be modified. Such factors might include process of care, including active involvement of full-time ICU physicians and length of hospital stay before ICU admission.DesignDemographic data, clinical diagnosis at ICU admission, Simplified Acute Physiology Score, and organizational characteristics were examined by logistic regression for their effect on ICU and hospital length of stay and weighted hospital days (WHD), a proxy for high cost of care.SettingA total of 34 ICUs at 27 hospitals participating in Project IMPACT during 1998.PatientsA total of 10,900 critically ill medical, surgical, and trauma patients qualifying for Simplified Acute Physiology Score assessment.InterventionsNone.ResultsOverall, 9.8% of patients had excess WHD, but the percentage varied by diagnosis. Factors predicting high WHD include Simplified Acute Physiology Score survival probability, age of 40 to 80 yrs, presence of infection or mechanical ventilation 24 hrs after admission, male sex, emergency surgery, trauma, presence of critical care fellows, and prolonged pre-ICU hospital stay. Mechanical ventilation at 24 hrs predicts high WHD across diagnostic categories, with a relative risk of between 2.4 and 12.9. Factors protecting against high WHD include do-not-resuscitate order at admission, presence of coma 24 hrs after admission, and active involvement of full-time ICU physicians.ConclusionsPatients with high WHD, and thus high costs, can be identified early. Severity of illness only partially explains high WHD. Age is less important as a predictor of high WHD than presence of infection or ventilator dependency at 24 hrs. Both long ward stays before ICU admission and lack of full-time ICU physician involvement in care increase the probability of long ICU stays. These latter two factors are potentially modifiable and deserve prospective study.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo evaluate a new antimicrobial treatment for central venous catheters in comparison with a traditional treatment, by assessing the catheter colonization and catheter-related bloodstream infection rates in two groups of patients.DesignMultiple-center, prospective randomized study.SettingThe medical and surgical departments of ten institutions.PatientsPatients requiring a central venous catheter for medical or surgical pathologies between June 2000 and November 2001.InterventionsPatients in the control group received a conventional benzalkonium-treated double-lumen central venous catheter, while patients in the oligon group received an oligon-treated (polyurethane combined with silver, carbon, and platinum) catheter with the same characteristics. Data collection included demographics, preexisting clinical conditions, main pathology, catheter insertion, and management data. Catheter colonization was defined as the growth of ≥15 colony-forming units in culture of catheter segments by the roll-plate method, or ≥1000 colony-forming units for the sonication method, and catheter-related bloodstream infection was defined as isolation of the same organism from the colonized catheter and from the peripheral blood of a patient with clinical signs of bloodstream infection.Measurements and Main ResultsData were obtained from 545 catheters. Of these, 132 catheters (24.2%) were positive for colonization. Patients in the oligon group demonstrated a lower risk for catheter colonization in the overall population (relative risk, 0.63; 95% confidence interval, 0.46–0.86;p= .003) and in the surgical subgroup (relative risk, 0.5; 95% confidence interval, 0.33–0.76;p= .001). Significant differences between groups were detected for coagulase-negative staphylococci and Gram-negative bacilli colonization rates. Twenty-one patients (3.8%) were positive for catheter-related bloodstream infection, without significant differences between control and oligon groups.ConclusionsOligon treatment is effective in limiting the catheter colonization rate. Due to the limited amount of events, this study lacked the power to detect significant differences in terms of catheter-related bloodstream infection rate.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionLife-sustaining treatments such as cardiopulmonary resuscitation, mechanical ventilation, vasopressors, and admission to critical care units, if used when recovery chance was remote, may unnecessarily cause discomfort and increase cost of care. Outcomes of these treatments in chronic, refractory congestive heart failure (CHF) and metastatic cancer patients were poor. Although both conditions were the leading causes of death, previous studies indicated that hospice utilization and do-not-resuscitate orders were less common in CHF patients. To date, the use of life-sustaining treatments in these patients and the influence of do-not-resuscitate orders remains unknown.MethodWe conducted a retrospective medical record review of the patients who died in our hospital in 1999 and had discharge diagnoses of CHF or cancer. Medical records were screened for seriously ill patients according to the modified SUPPORT criteria, which included patients with CHF functional class IV or ejection fraction of 20% or less at baseline and with metastatic cancer not receiving any curative treatments. Analyses were performed using SPSS, version 9.0.ResultsThere were 58 and 82 patients in CHF and cancer groups, respectively. CHF patients were older (78.8 vs. 67.3 yrs,p< .001) and stayed in the hospital longer (11.9 vs. 7.9 days,p= .014). The majority of patients in both groups received do-not-resuscitate orders before death (84% and 72%, respectively). CHF patients received do-not-resuscitate orders later than did cancer patients (6.7 vs. 2.8 days,p= .006). However, there was no significant difference in prevalence of do-not-resuscitate orders. All studied life-sustaining treatments were more common in CHF patients than in cancer patients. A subgroup analysis between CHF patients with do-not-resuscitate orders and those without do-not-resuscitate orders revealed cardiopulmonary resuscitation to be the only treatment less common in those with do-not-resuscitate orders.ConclusionsPatients who died of chronic, refractory CHF received more life-sustaining treatments than did patients who died of metastatic cancer.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesNitric oxide overproduction in sepsis syndrome was suspected to be responsible for hemodynamic derangement and, by induction of lipid peroxidation, for tissue damage. Therefore, nitric oxide formation and lipid peroxidation were quantified in septic patients (SP) vs. patients with localized infection (IF) or without inflammation (C). Nitric oxide formation in sepsis was additionally compared with data for clinical status.DesignProspective study with consecutive sampling of patients.SettingA university hospital intensive care unit and research laboratories.PatientsSP, 24 patients; IP, 7; and C, 13.InterventionsPlasma measurement of nitrate, lipid peroxides (primary endpoints), andN-hydroxy-l-arginine (secondary end point)Measurements and Main ResultsFor nitrate, there was a sequence of C < IP = SP. Among SP, one group with significantly higher nitrate (high-responders for nitric oxide; SP-HR) vs. IP and C and a second group (low-responders; SP-LR) with increased concentration only vs. C could be identified. For SP-HR vs. IP, a strong time kinetics in nitric oxide formation was obvious, indicated by significant nitrate increase already 1 day before sepsis started, tripling up to the peak concentration, and then a lowering but still increased value on the first day after sepsis.N-hydroxy-l-arginine was significantly increased in SP-HR vs. C. For lipid peroxides, the concentrations were comparable in SP and IP, but both significantly increased vs. C. Clustering and coincident kinetics of lipid peroxidation related to nitric oxide were not obvious. Furthermore, there was no strong correlation of clinical data and nitric oxide clustering in sepsis.ConclusionsHigh- and low-responders for nitric oxide were identified among septic patients. This finding was not associated with significant differences in lipid peroxidation or clinical data.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID