Cost-effectiveness of dalteparin vs unfractionated heparin for the prevention of venous thromboembolism in critically ill patients.

IMPORTANCE: Venous thromboembolism (VTE) is a common complication of acute illness, and its prevention is a ubiquitous aspect of inpatient care. A multicenter blinded, randomized trial compared the effectiveness of the most common pharmocoprevention strategies, unfractionated heparin (UFH) and the low-molecular-weight heparin (LMWH) dalteparin, finding no difference in the primary end point of leg deep-vein thrombosis but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia among critically ill medical-surgical patients who received dalteparin. OBJECTIVE: To evaluate the comparative cost-effectiveness of LMWH vs UFH for prophylaxis against VTE in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Prospective economic evaluation concurrent with the Prophylaxis for Thromboembolism in Critical Care Randomized Trial (May 2006 to June 2010). The economic evaluation adopted a health care payer perspective and in-hospital time horizon; derived baseline characteristics and probabilities of intensive care unit and in-hospital events; and measured costs among 2344 patients in 23 centers in 5 countries and applied these costs to measured resource use and effects of all enrolled patients. MAIN OUTCOMES AND MEASURES: Costs, effects, incremental cost-effectiveness of LMWH vs UFH during the period of hospitalization, and sensitivity analyses across cost ranges. RESULTS: Hospital costs per patient were $39,508 (interquartile range [IQR], $24,676 to $71,431) for 1862 patients who received LMWH compared with $40,805 (IQR, $24,393 to $76,139) for 1862 patients who received UFH (incremental cost, -$1297 [IQR, -$4398 to $1404]; P = .41). In 78% of simulations, a strategy using LMWH was most effective and least costly. In sensitivity analyses, a strategy using LMWH remained least costly unless the drug acquisition cost of dalteparin increased from $8 to $179 per dose and was consistent among higher- and lower-spending health care systems. There was no threshold at which lowering the acquisition cost of UFH favored prophylaxis with UFH. CONCLUSIONS AND RELEVANCE: From a health care payer perspective, the use of the LMWH dalteparin for VTE prophylaxis among critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH. These findings were driven by lower rates of pulmonary embolus and heparin-induced thrombocytopenia and corresponding lower overall use of resources with LMWH.

A randomised, controlled trial of conventional versus automated weaning from mechanical ventilation using SmartCare/PS.

OBJECTIVE: Preliminary assessment of an automated weaning system (SmartCare/PS) compared to usual management of weaning from mechanical ventilation performed in the absence of formal protocols. DESIGN AND SETTING: A randomised, controlled pilot study in one Australian intensive care unit. PATIENTS: A total of 102 patients were equally divided between SmartCare/PS and Control. INTERVENTIONS: The automated system titrated pressure support, conducted a spontaneous breathing trial and provided notification of success ("separation potential"). MEASUREMENTS AND RESULTS: The median time from the first identified point of suitability for weaning commencement to the state of "separation potential" using SmartCare/PS was 20 h (interquartile range, IQR, 2-40) compared to 8 h (IQR 2-43) with Control (log-rank P = 0.3). The median time to successful extubation was 43 h (IQR 6-169) using SmartCare/PS and 40 (14-87) with Control (log-rank P = 0.6). Unadjusted, the estimated probability of reaching "separation potential" was 21% lower (95% CI, 48% lower to 20% greater) with SmartCare/PS compared to Control. Adjusted for other covariates (age, gender, APACHE II, SOFAmax, neuromuscular blockade, corticosteroids, coma and elevated blood glucose), these estimates were 31% lower (95% CI, 56% lower to 9% greater) with SmartCare/PS. The study groups showed comparable rates of reintubation, non-invasive ventilation post-extubation, tracheostomy, sedation, neuromuscular blockade and use of corticosteroids. CONCLUSIONS: Substantial reductions in weaning duration previously demonstrated were not confirmed when the SmartCare/PS system was compared to weaning managed by experienced critical care specialty nurses, using a 1:1 nurse-to-patient ratio. The effect of SmartCare/PS may be influenced by the local clinical organisational context. DESCRIPTOR: 28. Mechanical ventilation: weaning.

Nutrition in the intensive care unit - you must breathe what you eat.

The imprecision in prescribing of enteral nutrition in critically ill patients must result in occasions of overfeeding as well as underfeeding. Overfeeding could cause increased CO2 production and thus increased work of breathing and prolonged ventilator dependence. This possibility is supported by the limited relevant literature. We examined this possibility mathematically using the data in The Augmented versus Routine Approach to Giving Energy Trial (TARGET) feasibility study and in its main study protocol. Patients in the energy-dense feeding arm will receive 50% more calories and produce 52% more CO2 than patients in the standard feeding arm. The full TARGET study is ideally positioned to answer the practical clinical question of whether increased feeding in critically ill patients can be delivered without prolonging ventilator dependence.

Helicobacter pylori in intensive care: why we should be interested.

Helicobacter pylori is estimated to infect over 50% of the world's population, the majority of whom are asymptomatic. Although most research to date has focused on local gastroduodenal disease manifestations, the potential impact of H. pylori infection and the associated chronic active inflammation on systemic disease processes is now being explored. This review addresses three aspects of emerging importance regarding H. pylori in intensive care medicine: acute gastric stress ulceration, nosocomial infection, and the potential modulatory effect on the systemic stress response. The role of H. pylori in acute stress ulceration remains uncertain, but it is unlikely to have the same major aetiological role as in peptic ulcer disease. The pathogenesis of both acute stress ulceration and H. pylori gastritis suggest overlapping mechanisms of gastric mucosal damage and H. pylori may augment stress ulceration incidence and severity. Nosocomial infection of both staff and patients with H. pylori has been suggested by serological studies, and increased H. pylori infection has been reported in intensive care staff. This has significant short- and long-term health implications and also raises questions regarding the efficacy and implementation of routine infection control precautions in intensive care. Finally, H. pylori infection has been linked with the pathogenesis of many extra-intestinal diseases, but the evidence is weak and the relationship between H. pylori and systemic diseases remains controversial. However, the potential for H. pylori to modulate systemic disease processes, particularly the systemic stress response in critical illness, is both theoretically plausible and therapeutically tantalising and requires further investigation.

Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial. METHODS/DESIGN: The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping. DISCUSSION: This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.

The role of general quality improvement measures in decreasing the burden of endemic MRSA in a medical-surgical intensive care unit.

PURPOSE: To determine whether any of several quality improvement interventions with none specifically targeting methicillin-resistant Staphylococcus aureus (MRSA) were associated with a decline in endemic MRSA prevalence in an intensive care unit (ICU) where active screening and contact isolation precautions for known MRSA colonised patients are not practised. SETTING: Medical-surgical ICU with 2,000 admissions/year. DESIGN: 8.5-year retrospective time-series analysis. INTERVENTIONS: ICU re-location, antibiotic stewardship utilising computerised decision-support and infectious-diseases physician rounds, dedicated ICU infection control practitioners, alcohol-based hand rub solution (ABHRS). METHOD: Regression modelling was used to evaluate trends in S. aureus prevalence density (monthly clinical isolates per 1,000 patient-days), antibiotic consumption, infection control consumables, ABHRS and their temporal relationship with MRSA prevalence. RESULTS: Methicillin-resistant S. aureus prevalence density decreased by 83% [95% confidence interval (CI) -68% to -91%, p < 0.001]. Rates of MRSA bacteraemia decreased 89% (95% CI -79% to -94%, p = 0.001) with no statistically significant change in methicillin-sensitive S. aureus bacteraemia. Hospital MRSA prevalence density decreased 17% (95% CI -5% to -27%, p = 0.005), suggesting that ICU was not shifting MRSA elsewhere. In ICU, broad-spectrum antibiotic use decreased by 26% (95% CI -12% to -38%, p = 0.008), coinciding with a decrease in MRSA, but time-series analysis did not show a significant association. On multivariate analysis, only ABHRS was significantly associated with a decrease in MRSA, but it was formally introduced late in the study period when MRSA was already in decline. CONCLUSION: General quality improvement measures were associated with a decrease in endemic MRSA in a high-risk setting without use of resource-intensive active surveillance and isolation practices.

Implementation of a multimodal infection control program during an Acinetobacter outbreak.

OBJECTIVES: Acinetobacter in the ICU presents a challenge worldwide due to its capacity for long-term survival on environmental surfaces. This report describes a multimodal infection control program designed to control a sustained outbreak Acinetobacter colonization. METHODS: Multimodal interventions implemented by unit-appointed infection control nurses in an Australian intensive care unit (ICU) during a sustained outbreak of Acinetobacter colonization. RESULTS: In the first 12 months of the outbreak, the mean monthly colonization rate was 3.1 (+/-1.2) cases per 100 bed-days (increased from 0.5 [+/-0.4] in the previous 6 months). In the subsequent 20-months, the mean monthly colonization rates declined to 1.5 (+/-1.5) cases per 100 bed-days (P=0.004). Hand hygiene compliance increased from 33% (95% CI 30-36%) before action plan implementation to 49% (95% CI 46-52%) measured 6-months after implementation. Compliance subsequently dropped to 39% (95% CI 36-42%) 12-months after implementation. The median volume of alcohol/chlorhexidine hand rub solution used per 1000 bed-days increased from 24L (interquartile range (IQR) 12-47L) to 148L (IQR 120-165L) per 1000 bed-days (P<0.001). CONCLUSIONS: Introduction of ICU-appointed infection control nurses, who then led multimodal interventions, was effective in reducing the rate of Acinetobacter colonization.

Acute stress ulceration prophylaxis: point prevalence surveys in intensive care units in Victoria, 1997 and 2005.

OBJECTIVE: To assess current practice in acute stress ulceration (ASU) prophylaxis in adult intensive care units in Victoria, Australia, in 1997 and 2005. METHODS: Point prevalence surveys using a structured telephone questionnaire of ASU prophylaxis practices were performed in adult ICUs in Victoria on 11 November 1997 and 13 April 2005. RESULTS: All Victorian ICUs identified on each study day participated, comprising 30 ICUs in 1997 and 35 ICUs in 2005. Presence of a clinical protocol or guideline for ASU prophylaxis increased significantly from 23% in 1997 to 54% in 2005 (P = 0.01). Overall provision of ASU prophylaxis to ICU patients also increased significantly from 67% in 1997 to 86% in 2005 (P < 0.001). H2-receptor antagonists were the preferred first-line agent in at least 50% of ICUs, and were also the most commonly used agents in both point prevalence surveys, with no change over 8 years. Use of proton-pump inhibitors increased significantly, both as first-line ASU prophylaxis agents and in clinical use, from 13% in 1997 to 45% in 2005 (P < 0.001). Use of sucralfate and antacids for ASU prophylaxis ceased between 1997 and 2005. CONCLUSIONS: Use of ASU prophylaxis for patients admitted to Victorian ICUs increased significantly from 1997 to 2005, with an associated increase in the presence of protocols or guidelines for ASU prophylaxis. Although agents currently used for ASU prophylaxis in Victorian ICUs are consistent with available evidence, we are concerned that ASU prophylaxis is given to all patients admitted to the ICU rather than targeted to patients in high-risk categories.

Reduction of broad-spectrum antibiotic use with computerized decision support in an intensive care unit.

OBJECTIVE: To implement and evaluate the effect of a computerized decision support tool on antibiotic use in an intensive care unit (ICU). DESIGN: Prospective before-and-after cohort study. SETTING: Twenty-four bed tertiary hospital adult medical/surgical ICU. PARTICIPANTS: All consecutive patients from May 2001 to November 2001 (N = 524) and March 2002 to September 2002 (N = 536). INTERVENTION: A real-time microbiology browser and computerized decision support system for isolate directed antibiotic prescription. MAIN OUTCOME MEASURES: Number of courses of antibiotic prescribed, antibiotic utilization (defined daily doses (DDDs)/100 ICU bed-days), antibiotic susceptibility mismatches, and system uptake. RESULTS: There was a significant reduction in the proportion of patients prescribed carbapenems [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.39-0.97, P = 0.04], third-generation cephalosporins (OR = 0.58, 95% CI = 0.42-0.79, P = 0.001), and vancomycin (OR = 0.67, 95% CI = 0.45-1.00, P = 0.05) after adjustment for risk factors including Apache II score, suspected infection, positive microbiology, intubation, and length of stay. The decision support tool was associated with a 10.5% reduction in both total antibiotic utilization (166-149 DDDs/100 ICU bed days) and the highest volume broad-spectrum antibiotics. There were fewer susceptibility mismatches for initial antibiotic therapy (OR = 0.63, 95% CI = 0.39-0.98, P = 0.02) and increased de-escalation to narrower spectrum antibiotics. Uptake of the program was high with 6028 access episodes during the 6-month evaluation period. CONCLUSIONS: This tool streamlined collation and clinical use of microbiology results and integrated into the daily ICU workflow. Its introduction was accompanied by a reduction in both total and broad-spectrum antibiotic use and an increase in the number of switches to narrower spectrum antibiotics.

Epidemiology of sepsis in Victoria, Australia.

OBJECTIVE: To determine the clinical and epidemiologic characteristics of patients with sepsis admitted to hospitals in Victoria, Australia, including the incidence of sepsis and severe sepsis, utilization of intensive care unit (ICU) resources, and hospital mortality. DESIGN: A population-based hospital morbidity database generated from hospital discharge coding. SETTING: State of Victoria, Australia (population, 4.5 million), the 4-yr period from July 1, 1999, to June 30, 2003. PATIENTS: A total of 3,122,515 overnight hospitalizations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall hospital incidence of sepsis was 1.1%, with a mortality of 18.4%. Of septic patients, 23.8% received some care in an ICU. For these patients, hospital mortality was 28.9%. Severe sepsis, defined by sepsis and at least one organ dysfunction, occurred in 39% of sepsis patients and was accompanied by a hospital mortality of 31.1%. Fifty percent of patients with severe sepsis received at least some care in an ICU. CONCLUSIONS: Australian state hospital administrative data reveal epidemiologic features of sepsis and severe sepsis that are strikingly similar to those recently reported from comparable populations in North American and Europe. This suggests that lessons learned in this area may be directly applicable internationally.

A randomized phase II trial of granulocyte-macrophage colony-stimulating factor therapy in severe sepsis with respiratory dysfunction.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates hemopoiesis and effector functions of granulocytes and macrophages and is involved in pulmonary surfactant homeostasis. We investigated whether GM-CSF therapy improved clinically diagnosed severe sepsis and respiratory dysfunction in critically ill patients. This randomized, double-blind, placebo-controlled phase II study added low-dose (3 mcg/kg) intravenous recombinant human GM-CSF daily for 5 days to conventional therapy in 10 patients, with a further eight patients receiving placebo. GM-CSF-treated patients showed improvement in Pa(O(2))/FI(O(2)) over 5 days (p = 0.02) and increased peripheral blood neutrophils (p = 0.08), whereas alveolar neutrophils decreased (p = 0.02). GM-CSF therapy was not associated with decreased 30-day survival or with increased acute respiratory distress syndrome or extrapulmonary organ dysfunction. GM-CSF therapy was associated with increased blood granulocyte superoxide production and restoration or preservation of blood and alveolar leukocyte phagocytic function. We conclude that low-dose GM-CSF was associated with improved gas exchange without pulmonary neutrophil infiltration, despite functional activation of both circulating neutrophils and pulmonary phagocytes. In addition, GM-CSF therapy was not associated with worsened acute respiratory distress syndrome or the multiple organ dysfunction syndrome, suggesting a homeostatic role for GM-CSF in sepsis-related pulmonary dysfunction.

Tratamiento de infecciones severas de las vías respiratorias / Processing of severe infections of the respiratory channels

Expone que la dosificación antibiótica óptima en infecciones severas de las vías respiratorias no está establecida y los regímenes comúnmente usados pueden muy bien ser excesivos. Hemos comparado la eficacia de una dosis baja de cefotaxima (2g. cada 12 h.) con una dosis más usual (2g. cada 8h.), en un estudio prospectivo y randomizado del tratamiento de estas infecciones en el paciente seriamente enfermo. Durante 5 días, 50 pacientes de la unidad de cuidados intensivos, recibieron cualquiera de los dos regímenes. Los dos grupos fueron demográficamente comparables. La resolusión clínica ocurrió en un 86xciento de pacientes, en un 4xciento no se produjo cambio alguno y en el 10xciento restante se presentó un deterioro. La depuración microbiológica ocurrió en el 52xciento de aquellos en quienes se aisló un patógeno (46xciento de pacientes). No hubo diferencia significativa en la respuesta clínica o microbiológica entre los dos regímenes. Se concluye que cefotaxima, a la dosis de 2g. dos veces al día, es efectiva en el tratamiento de infecciones severas de las vías respiratorias.