Noninvasive positive pressure ventilation in the setting of severe, acute exacerbations of chronic obstructive pulmonary disease: more effective and less expensive.

OBJECTIVE: The use of noninvasive ventilation for patients with acute respiratory failure has become increasingly popular over the last decade. Although the literature provides good evidence for the effectiveness of noninvasive ventilation in addition to standard therapy compared with standard therapy alone in patients with chronic obstructive pulmonary disease (avoiding intubation and improving hospital mortality), the associated costs have not been rigorously measured. Adding noninvasive positive pressure ventilation (NPPV) to standard therapy in the setting of a severe, acute exacerbation of chronic obstructive pulmonary disease (COPD) in patients with respiratory acidosis who are at high risk of requiring endotracheal intubation is both more effective and less expensive. DESIGN: Economic evaluation based on theoretical model. SETTING: This analysis base case was modeled for a tertiary care, teaching hospital. PATIENTS OR OTHER PARTICIPANTS: Carefully selected patients with severe exacerbations of COPD. INTERVENTION: The two alternative therapies compared were standard therapy (oxygen, bronchodilators, steroids, and antibiotics) and standard therapy plus NPPV. MEASUREMENTS AND MAIN RESULTS: As the hypothesis was dominance, the main outcomes modeled and calculated were costs, mortality rate, and rates of intubation between the two interventions. To determine clinical effectiveness, we used a meta-analysis of randomized trials evaluating the impact of NPPV on hospital survival. A decision tree was constructed and probabilities were applied at each chance node using research evidence and a comprehensive regional database. To provide data for this economic evaluation, MEDLINE literature searches were conducted. Bibliographies of relevant articles were reviewed, as were personal files. To estimate the costs of the alternative therapeutic approaches, eight types of hospitalization days were costed using the London Health Sciences Center costing data. Sensitivity analyses were performed, varying all assumptions made. The meta-analysis yielded an odds ratio for hospital mortality in the NPPV arm, compared with standard therapy, of 0.22 (95% confidence interval, 0.10-0.66). By using baseline case assumptions, we found a cost savings of $3,244 (1996, Canadian), per patient admission, if NPPV were adopted in favor of standard therapy. These findings present a scenario of clear dominance for treatment with NPPV. Sensitivity analyses did not alter the results appreciably. CONCLUSIONS: We conclude that from a hospital's perspective, NPPV and standard therapy for carefully selected patients with acute, severe exacerbations of COPD are more effective and less expensive than standard therapy alone.

The Critical Care Research Network: a partnership in community-based research and research transfer.

The objectives of this study were to present a short history of the Critical Care Research Network (CCR-Net), describe its approach to health services research and to summarize completed and current research projects. In doing this, we explored the question is this research network accomplishing its goals? We reviewed the medical literature to identify studies on similar types of Networks and also the evidence supporting the methodology used by CCR-Net to conduct research using MEDLINE, HEALTHSTAR, CINAHL and the keywords network and health care or healthcare, benchmarking and health care or healthcare, and research transfer or research utilization. We also reviewed the bibliographies of retrieved articles and our personal files. In addition, we summarized the results of studies conducted by CCR-Net and outlined those currently in progress. A review of the literature identified studies on two similar networks that appeared to be succeeding. In addition, the literature was also supportive of the general process used by CCR-Net, although the level of evidence varied. Finally, the studies conducted to date within CCR-Net follow the suggested methodology. At the time of this preliminary communication CCR-Net appears to have adopted a valid approach to health services research within the area of Critical Care Medicine. Further direct evidence is required and appropriate studies are planned.

An alternative pathway for preclinical research in fluid management.

Recent meta-analyses have created uncertainties regarding the appropriate clinical role of colloid resuscitation fluids in critically ill patients and prompted changes in fluid management practice. Such changes may not be justified in view of methodological limitations inherent in the meta-analyses. Further research is nevertheless needed to resolve the questions raised concerning the relationship between choice of resuscitation fluid and patient outcome. Animal studies can play an important part by reliably indicating whether particular fluids are likely to prove effective and safe in clinical trials. It is important to avoid costly large-scale clinical trials that fail to demonstrate the clinical utility of the tested therapy, as resources expended in failed trials raise overall development costs and thereby restrict the range of therapies meeting criteria of commercial feasibility. Promising therapies may thus not be pursued, even though an urgent clinical need may exist. An alternative pathway of preclinical research may be of value in avoiding some of the major clinical trial failures of recent years, particularly in the area of sepsis. This alternative pathway commences with the formulation of hypotheses by therapeutics developers. Independent preclinical investigators are challenged, by means of a competitive request for proposals, to test the hypotheses in rigorous randomized studies employing clinically relevant animal models. Promising proposals would then be selected for further development with the aid of peer review. The results of the randomized animal studies, along with other preclinical data, could also be evaluated using accepted principles of 'critical appraisal' commonly applied to clinical trial results. This critical appraisal might, where appropriate, include meta-analysis of animal study findings. This alternative preclinical pathway to new product evaluation should be completed before the commencement of large-scale clinical trials.

Dopexamine attenuates flow motion in ileal mucosal arterioles in normotensive sepsis.

OBJECTIVES: Injury to the small intestine is thought to play a crucial role in the development and propagation of sepsis. Cellular hypoxia, caused by hypoperfusion, may result in increased mucosal permeability, thus allowing the translocation of bacteria and endotoxin to the circulation. The purpose of this study was to assess the effect of the synthetic catecholamine, dopexamine, on the mucosal microcirculation of the septic rat ileum. DESIGN: Randomized, crossover study. SETTING: Teaching hospital animal laboratory. SUBJECTS: Sprague-Dawley male rats. INTERVENTIONS: Sepsis was induced by cecal ligation and perforation in 11 male Sprague-Dawley rats. Six sham animals were also studied. At 24 hrs, rats were anaesthetized, intubated, ventilated, and prepared for intravital microscopy of the mucosal surface of the ileum. Dopexamine (8 microg/kg/min) and saline were infused intravenously into each rat using a randomized crossover design. MEASUREMENTS AND MAIN RESULTS: Observations were videotaped for later analysis of arteriolar flow patterns, red cell velocity, arteriolar diameter, and intercapillary area. All values are expressed as mean +/- SEM. The main effect of dopexamine infusion in the sepsis group was the attenuation of the rhythmic blood flow patterns (flow motion) observed during saline infusion. In each subject, dopexamine decreased the absolute number of arterioles exhibiting flow motion by 35.93+/-6.81% (p<.001, paired t-test). Dopexamine decreased the amount of time red cell flow was stopped in marginal and central arterioles by 11.83+/-2.49% (p<.001, paired t-test). Dopexamine did not alter significantly the diameter of the marginal arterioles, the intercapillary area, or the red cell velocity compared with saline in the sepsis group. The sham group displayed marked microvascular differences compared with the sepsis group with respect to arteriolar diameter (13.32+/-0.05 vs. 9.46+/-0.24 mm, p<.001), intercapillary area (975.93+/-60.60 vs. 1256.03+/-43.88 mm2, p<.05 ), red cell velocity (611.40+/-38.77 vs. 289.15+/-36.45, p<.001), and blood flow patterns (% displaying flow motion, 15.89+/-6.09 vs. 58.22+/-9.63, p<.01; % time stopped flow, 1.96+/-0.89 vs. 20.21+/-3.92, p<.005). CONCLUSIONS: These results indicate that dopexamine increased overall blood flow and possibly oxygen delivery to the mucosa by altering patterns of blood flow within the villi. The observation that the diameter of the marginal arterioles is not affected by dopexamine indicates that dopexamine influences the mucosal microcirculation at the level of higher order arterioles. We conclude that sepsis results in abnormal microvascular villus blood flow and that dopexamine can partially restore these changes towards normal.

Alveolo-capillary permeability in human septic ARDS. Effect of high-dose corticosteroid therapy.

High-dose corticosteroid therapy has been advocated as adjunctive therapy in the adult respiratory distress syndrome (ARDS). We evaluated the effect of pharmacologic doses of corticosteroid (methylprednisolone and dexamethasone) on alveolo-capillary permeability in human septic ARDS by examining the change in appearance of intravenously administered iodine 131 (131I) human serum albumin (I-HSA) into broncho-alveolar secretions, before and after corticosteroid administration. Of 19 patients examined, in 14 (group 1) the clearance of I-HSA was reduced by corticosteroid (pre, .204 +/- .08 ml;/hr; post, .096 +/- .01 ml/hr; P less than .001), while in five (group 2) it was unaffected (pre, .23 +/- .02 ml/hr; post, .215 +/- .01 ml/hr; P=NS). Group 2 patients were more severely ill than group 1 patients in that their mean intrapulmonary shunt fractions and mean pulmonary artery pressures were higher. We conclude that high-dose corticosteroid therapy may reduce alveolo-capillary permeability in human septic ARDS if used early in the course of the illness.