Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis with multiple organ failure.

OBJECTIVES: The aim of this study was to estimate the expected cost and clinical benefits associated with the use of drotrecogin alfa (activated) (Xigris; Eli Lilly and Company; Indianapolis, IN) in the French hospital setting. METHODS: The recombinant human activated PROtein C Worldwide Evaluation in Severe Sepsis (PROWESS) study results (1271 patients with multiple organ failure) were adjusted to 9,948 hospital stays from a database of Parisian area intensive-care units (ICUs)-the CubRea (Intensive Care Database User Group) database. The analysis features a decision tree with a probabilistic sensitivity analysis. RESULTS: The cost per life year gained (LYG) of drotrecogin treatment for severe sepsis with multiple organ failure (European indication) was estimated to be dollars 11,812. At the hospital level, the drug is expected to induce an additional cost of dollars 7545 per treated patient. The incremental cost-effectiveness ratio ranges from dollars 7873 per LYG for patients receiving three organ supports during ICU stay to dollars 17,704 per LYG for patients receiving less than two organ supports. CONCLUSIONS: Drotrecogin alfa (activated) is cost-effective in the treatment of severe sepsis with multiple organ failure when added to best standard care. The cost-effectiveness of the drug increases with baseline disease severity, but it remains cost-effective for all patients when used in compliance with the European approved indication.

[Meningitis caused by Enterococcus faecalis during disseminated anguilluliasis]. / Méningite à Enterococcus faecalis au cours d'une anguillulose disséminée.

INTRODUCTION: Disseminated anguilluliasis is a serious disease requiring early diagnosis and treatment. The occurrence of bacterial complications, especially meningeal, is generally due to Gram-negative bacteria from the gastrointestinal tract. CASE: A 52-year-old man from Guadeloupe, treated for T-lymphoma during the previous year by polychemotherapy, was hospitalized for meningitis. Culture of the cerebrospinal fluid and the bronchoalveolar lavage both showed Enterococcus faecalis. Strongyloides stercoralis were also found in the stool and bronchoalveolar lavage. Outcome under treatment was favorable. DISCUSSION: This case reminds us of the usefulness of presumptive routine ivermectin treatment for all patients exposed to any immunosuppression treatment and ever having lived in a tropical area and thus possibly infected by chronic but silent anguilluliasis, even in the absence of parasitological certainty.

Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost.

PURPOSE: Severe sepsis is a leading cause of death in critically ill patients. We evaluated cost and workload according to infection site, place and time of acquisition, and severity. MATERIAL AND METHOD: We used a prospective 3-year database from 6 intensive care units (ICUs) including 1698 patients. RESULTS: Of the 1698 patients, 713 (42%) had severe sepsis at admission and 339 during the ICU stay (211 had both). Mortality was twice as high in patients with than those without ICU-acquired infection, independent of the presence of severe sepsis at admission. The mean (SD; median) cost of severe sepsis was 22 800 (21 400 ; 15 800 ). Among patients with severe sepsis at admission, workload and cost were higher for pneumonia, peritonitis, and multiple-site infections and for hospital-acquired (17,400 [14,700; 17,400]) vs community-acquired infection (12,600 [12,100 ; 8900 ]). Intensive care unit-acquired severe sepsis was associated with greater than 3-fold increases in workload and costs. By multiple linear regression, older age, emergency surgery, septic shock, Acute Physiological and Chronic Health Evaluation II score, and hospital or ICU-acquired severe sepsis were independently associated with higher costs. CONCLUSIONS: The wide variations in cost and workload invite efforts to identify patient subgroups most likely to benefit from high-cost treatments and from prevention, particularly targeting severe nosocomial infections.

Incidence and impact of organ dysfunctions associated with sepsis.

OBJECTIVE: To study the incidence and severity of organ dysfunction associated with sepsis. DESIGN: Comprehensive review of prospectively collected data from intensive care patients hospitalized between 1997 and 2001. SETTING: Thirty-five ICUs in nonuniversity and university hospitals located in the Paris area. PATIENTS: All patients hospitalized in the ICU for > 24 h meeting the criteria for severe sepsis (SS), either with only one organ dysfunction present during the ICU stay (SS1; n = 5,675) or with at least two organ dysfunction present during the ICU stay (SS2; n = 12,598), were compared to all other patients hospitalized for > 24 h in the ICU over the same time period (n = 47,637). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected information on demographic characteristics, type of admission, underlying disease, organ dysfunction, organ support, McCabe and Charlson-Deyo scores, simplified acute physiology score II, length of stay, and outcome. The incidence of SS was 27.7% (8.6% for SS1 and 19.1 for SS2). Compared with non-SS patients, those with SS were significantly older, were more frequently men, required organ support more frequently, had higher severity scores, and stayed longer in the ICU and hospital. Respiratory and cardiovascular dysfunction and fungal infection were strong independent risk factors for death in SS patients, with 5.64-fold, 4.35-fold, and 2.0-fold increased risks, respectively. SS2 is significantly different from SS1: older age, more surgical stays and admission from external transfer, greater number of organ supports, site of infection (less pulmonary and urinary tract infections, and more abdominal and cardiovascular infections), type of bacteria (more methicillin-resistant Staphylococcus aureus, Pseudomonas, and fungus), ICU length of stay (20.4 d vs 11.6 d), hospital length of stay (33 d vs 27.9 d), ICU mortality (42.7% vs 5.5%), and hospital mortality (49% vs 11.3%). CONCLUSIONS: Our study identifies a subgroup of patients with an ICU stay > 24 h and SS with at least two organ dysfunctions. This group of patients requires special attention since their ICU mortality is > 40% and they occupy almost 40% of all ICU beds.

Proportional-assist ventilation compared with pressure-support ventilation during exercise in volunteers with external thoracic restriction.

OBJECTIVES: Proportional-assist ventilation (PAV) is able to unload respiratory muscles in proportion to the subject's inspiratory effort. However, leak-related alterations in the flow signal, effort-induced modifications in respiratory mechanics, or approximate adjustment of PAV could jeopardize such a theory. The aim of this study was to compare noninvasive PAV and pressure-support ventilation (PSV) in healthy volunteers with external thoracic restriction at rest and during exercise. DESIGN: Prospective, crossover, randomized study. SETTING: Investigation unit in a nonteaching hospital. PATIENTS: Seven volunteers with external thoracic restriction. INTERVENTION: After external thoracic restriction to increase elastance (9.00 +/- 1.63 cm H2O/L estimated from the level of elastic assistance), PAV and PSV were compared at rest and during exercise (90 W for 10 mins). MEASUREMENTS AND MAIN RESULTS: Flow, airway pressure, and changes in esophageal pressure were measured, and the tidal volume (Vt) and inspiratory muscle effort indexes were calculated. At rest, all variables were comparable during PSV and PAV. Exercise produced a 200% increased in Vt with no change in the breathing frequency and a 400% increased in inspiratory muscle effort indexes. During exercise, peak inspiratory airway pressure was significantly higher with PAV than with PSV (24 +/- 5 vs. 10 +/- 2 cm H2O, p <.05). The Vt and breathing frequency (23 +/- 4 vs. 24 +/- 3 breaths/min) were similar, but the inspiratory muscle effort indexes were significantly lower with PAV than with PSV. A significant linear correlation was found between changes in esophageal pressure and the peak inspiratory airway pressure during PAV (r =.94, p =.0001), whereas, as expected, it was not the case during PSV (r =.27, p =.34). CONCLUSION: In volunteers with external thoracic restriction mimicking a patient with increased elastic work of breathing, the breathing pattern at rest and during exercise were comparable with PSV and PAV, whereas inspiratory muscle effort was lower with PAV during exercise because of the significant automatic increase in assistance with PAV.

Noninvasive proportional assist ventilation compared with noninvasive pressure support ventilation in hypercapnic acute respiratory failure.

OBJECTIVES: To compare short-term administration of noninvasive proportional assist ventilation (NIV-PAV) and pressure support ventilation (NIV-PSV). DESIGN: Prospective, crossover, randomized study. SETTING: Medicosurgical intensive care unit in a nonteaching hospital. PATIENTS: Twelve chronic obstructive pulmonary disease patients admitted for hypercapnic acute respiratory failure. INTERVENTION: NIV-PSV and NIV-PAV given in a randomized order after baseline evaluation in continuous positive airway pressure. Using a flow-triggering ventilator, NIV-PAV was adjusted using the runaway method and compared with NIV-PSV at similar peak inspiratory airway pressure. MEASUREMENTS AND MAIN RESULTS: Flow, airway pressure, and changes in esophageal pressure were measured and the tidal volume, the patient's inspiratory work of breathing, and the esophageal pressure--time product were calculated. Arterial pH and PaCO(2) were measured and breathing comfort was assessed using a visual analogic scale. Peak inspiratory airway pressure (17 +/- 3 cm H(2)O) and tidal volume were similarly increased with the two modalities with no change in respiratory rate. The change in esophageal pressure was similarly decreased (from 20 +/- 8 cm H(2)O in continuous positive airway pressure to 12 +/- 7 in NIV-PSV and 10 +/- 5 cm H(2)O in NIV-PAV) as well as inspiratory muscle effort indexes. Arterial pH and PaCO(2) were similarly improved. Breathing comfort was significantly improved in NIV-PAV (+38 +/- 38%) but not in NIV-PSV (+11 +/- 23%). The tidal volume was more variable in NIV-PAV (89 +/- 18%) than in NIV-PSV (15 +/- 8%) and changes in tidal volume variability were significantly correlated (p =.02) with changes in breathing comfort. CONCLUSIONS: In chronic obstructive pulmonary disease patients with hypercapnic acute respiratory failure, NIV-PAV was able to unload inspiratory muscles similarly to NIV-PSV but may be more comfortable than NIV-PSV.