Sepsis-coded hospitalisations and associated costs in Australia: a retrospective analysis.

OBJECTIVE: To report trends in Australian hospitalisations coded for sepsis and their associated costs. DESIGN: Retrospective analysis of Australian national hospitalisation data from 2002 to 2021. METHODS: Sepsis-coded hospitalisations were identified using the Global Burden of Disease study sepsis-specific ICD-10 codes modified for Australia. Costs were calculated using Australian-Refined Diagnosis Related Group codes and National Hospital Cost Data Collection. RESULTS: Sepsis-coded hospitalisations increased from 36,628 in 2002-03 to 131,826 in 2020-21, an annual rate of 7.8%. Principal admission diagnosis codes contributed 13,843 (37.8%) in 2002-03 and 44,186 (33.5%) in 2020-21; secondary diagnosis codes contributed 22,785 (62.2%) in 2002-03 and 87,640 (66.5%) in 2020-21. Unspecified sepsis was the most common sepsis code, increasing from 15,178 hospitalisations in 2002-03 to 68,910 in 2020-21. The population-based incidence of sepsis-coded hospitalisations increased from 18.6 to 10,000 population (2002-03) to 51.3 per 10,000 (2021-21); representing an increase from 55.1 to 10,000 hospitalisations in 2002-03 to 111.4 in 2020-21. Sepsis-coded hospitalisations occurred more commonly in the elderly; those aged 65 years or above accounting for 20,573 (55.6%) sepsis-coded hospitalisations in 2002-03 and 86,135 (65.3%) in 2020-21. The cost of sepsis-coded hospitalisations increased at an annual rate of 20.6%, from AUD199M (€127 M) in financial year 2012 to AUD711M (€455 M) in 2019. CONCLUSION: Hospitalisations coded for sepsis and associated costs increased significantly from 2002 to 2021 and from 2012 to 2019, respectively.

Long-term costs and cost-effectiveness of adjunctive corticosteroids for patients with septic shock in New Zealand.

OBJECTIVE: The aim of the study was to determine whether adjunctive hydrocortisone reduced healthcare expenditure and was cost-effective compared with placebo in New Zealand patients in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. DESIGN: This is a health economic analysis using data linkage to New Zealand Ministry of Health databases to determine resource use, costs, and cost-effectiveness for a 24-month period. SETTING: The study was conducted in New Zealand. PARTICIPANTS AND INTERVENTION: Patients with septic shock were randomised to receive a 7-day continuous infusion of 200 mg of hydrocortisone or placebo in the ADRENAL trial. MAIN OUTCOME MEASURES: Healthcare expenditure was associated with all hospital admissions, emergency department presentations, outpatient visits, and pharmacy expenditure. Effectiveness outcomes included mortality at 6 months and 24 months and quality of life at 6 months. Cost-effectiveness outcomes were assessed with reference to quality-adjusted life years gained at 6 months and life years gained at 24 months. RESULTS: Of 3800 patients in the ADRENAL trial, 419 (11.0%) were eligible, and 405 (96.7% of those eligible) were included. The mean total costs per patient over 24 months were $143,627 ± 100,890 and $143,772 ± 97,117 for the hydrocortisone and placebo groups, respectively (p = 0.99). Intensive care unit costs for the index admission were $50,492 and $62,288 per patient for the hydrocortisone and placebo groups, respectively (p = 0.09). The mean number of quality-adjusted life years gained at 6 months and mean number of life years gained at 24 months was not significantly different by treatment group, and the probability of hydrocortisone being cost-effective was 55% at 24 months. CONCLUSIONS: In New Zealand, adjunctive hydrocortisone did not reduce total healthcare expenditure or improve outcomes compared with placebo in patients with septic shock.

Incidence and outcomes of sepsis in Aboriginal and Torres Strait Islander and non-Indigenous residents of New South Wales: population-based cohort study.

Objective: To estimate the incidence and outcomes of sepsis hospitalisations in Aboriginal and Torres Strait Islander and non-Indigenous residents of New South Wales. Design and participants: Prospective cohort study of residents aged 45 years and older, recruited between 2006 and 2009, and followed for hospitalisation for sepsis. Main outcome measures: Incidence and hazard ratio (HR) of sepsis hospitalisation and intensive care unit (ICU) admission identified using International Classification of Diseases (10th revision) coding on discharge data. Length of stay, readmission and mortality in those admitted for sepsis. Results: Of 264 678 participants, 1928 (0.7%) identified as Aboriginal and/or Torres Strait Islander. Sepsis hospitalisation was higher in Aboriginal and Torres Strait Islander participants (8.67 v 6.12 per 1000 person-years; age- and sex-adjusted HR, 2.35; 95% CI, 1.98-2.80) but was attenuated after adjusting for sociodemographic factors, health behaviour and comorbidities (adjusted HR, 1.56; 95% CI, 1.31-1.86). Among those hospitalised for sepsis, after adjusting for age and sex, there were no differences between the proportions of Aboriginal and Torres Strait Islander and non-Indigenous participants admitted to an ICU (18.0% v 16.1%; P = 0.42) or deceased at 1 year (36.1% v 36.8%; P = 0.92). Aboriginal and Torres Strait Islander participants had shorter lengths of hospital stay (9.98 v 11.72 days; P < 0.001) and ICU stay (4.38 v 6.35 days; P < 0.001) than non-Indigenous participants. Overall, more than 70% of participants were readmitted to hospital within 1 year. Conclusion: We found that the rate of sepsis hospitalisation in NSW was higher for Aboriginal and Torres Strait Islander adults. Culturally appropriate, community-led strategies targeting chronic disease prevention and the social determinants of health may reduce this gap. Preventing readmission following sepsis is a priority for all Australians.

An international comparison of the cost of fluid resuscitation therapies.

OBJECTIVE: Fluid resuscitation is a ubiquitous intervention in the management of patients treated in the intensive care unit, which has implications for intensive care unit resourcing and budgets. Our objective was to calculate the relative cost of resuscitation fluids in several countries to inform future economic evaluations. METHODS: We collected site-level data regarding the availability and cost of fluids as part of an international survey. We normalised costs to net present values using purchasing power parities and published inflation figures. Costs were also adjusted for equi-effective dosing based on intravascular volume expansion effectiveness and expressed as US dollars (USD) per 100 mL crystalloid equivalent. RESULTS: A total of 187 sites had access to cost data. Between countries, there was an approximate six fold variation in the cost of crystalloids and colloids overall. The average cost for crystalloids overall was less than 1 USD per 100 mL. In contrast, colloid fluids had higher average costs (59 USD per 100 mL). After adjusting for equi-effective dosing, saline was ∼27 times less costly than albumin (saline: 0.6 USD per 100 mL crystalloid equivalent; albumin 4-5%: 16.4 USD; albumin 20-25%: 15.8 USD) and ∼4 times less costly than hydroxyethyl starch solution (saline: 0.6 USD; hydroxyethyl starch solution: 2.5 USD). Buffered salt solutions, such as compound sodium acetate solutions (e.g., Plasmalyte®), had the highest average cost of crystalloid fluids, costing between 3 and 4 USD per 100 mL. CONCLUSION: The cost of fluid varies substantially between fluid types and between countries, although normal (0.9%) saline is consistently less costly than colloid preparations and some buffered salt solutions. These data can be used to inform future economic evaluations of fluid preparations.

The cost-effectiveness of adjunctive corticosteroids for patients with septic shock.

OBJECTIVE: To determine whether hydrocortisone is a cost-effective treatment for patients with septic shock. DESIGN: Data linkage-based cost-effectiveness analysis. SETTING: New South Wales and Queensland intensive care units. PARTICIPANTS AND INTERVENTION: Patients with septic shock randomly assigned to treatment with hydrocortisone or placebo in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. MAIN OUTCOME MEASURES: Health-related quality of life at 6 months using the EuroQoL 5-dimension 5-level questionnaire. Data on hospital resource use and costs were obtained by linking the ADRENAL dataset to government administrative health databases. Clinical outcomes included mortality, health-related quality of life, and quality-adjusted life-years gained; economic outcomes included hospital resource use, costs and cost-effectiveness from the health care payer perspective. We also assessed cost-effectiveness by sex. To increase the precision of cost-effectiveness estimates, we conducted unrestricted bootstrapping. RESULTS: Of 3800 patients in the ADRENAL trial, 1772 (46.6%) were eligible and 1513 (85.4% of those eligible) were included. There was no difference between hydrocortisone or placebo groups in regards to mortality (218/742 [29.4%] v 227/759 [29.9%]; HR, 0.93; 95% CI, 0.78-1.12; P = 0.47), mean number of QALYs gained (0.10 ± 0.09 v 0.10 ± 0.09; P = 0.52), or total hospital costs (A$73 515 ± 61 376 v A$69 748 ± 61 793; mean difference, A$3767; 95% CI, -A$2891 to A$10 425; P = 0.27). The incremental cost of hydrocortisone was A$1 254 078 per quality-adjusted life-year gained. In females, hydrocortisone was cost-effective in 46.2% of bootstrapped replications and in males it was cost-effective in 2.7% of bootstrapped replications. CONCLUSIONS: Adjunctive hydrocortisone did not significantly affect longer term mortality, health-related quality of life, health care resource use or costs, and is unlikely to be cost-effective.

Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study.

BACKGROUND: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. METHODS: We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990-2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. FINDINGS: In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9-62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1-12·0) sepsis-related deaths were reported, representing 19·7% (18·2-21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8-54·5) and mortality decreased by 52·8% (47·7-57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. INTERPRETATION: Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. FUNDING: The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

Women in Intensive Care study: a preliminary assessment of international data on female representation in the ICU physician workforce, leadership and academic positions.

BACKGROUND: Despite increasing female enrolment into medical schools, persistent gender gaps exist in the physician workforce. There are limited published data on female representation in the critical care medicine workforce. METHODS: To obtain a global perspective, societies (n = 84; 79,834 members (40,363 physicians, 39,471 non-physicians)) registered with the World Federation of Societies of Intensive and Critical Care Medicine were surveyed. Longitudinal data on female trainee and specialist positions between 2006-2017 were obtained from Australia and New Zealand. Data regarding leadership and academic faculty representation were also collected from national training bodies and other organisations of critical care medicine. RESULTS: Of the 84 societies, 23 had a registered membership of greater than 500 members. Responses were received from 27 societies (n = 55,996), mainly high-income countries, covering 70.1% of the membership. Amongst the physician workforce, the gender distribution was available from six (22%) participating societies-mean proportion of females 37 ± 11% (range 26-50%). Longitudinal data from Australia and New Zealand between 2006 and 2017 demonstrate rising proportions of female trainees and specialists. Female trainee and specialist numbers increased from 26 to 37% and from 13 to 22% respectively. Globally, female representation in leadership positions was presidencies of critical care organisations (0-41%), representation on critical care medicine boards and councils (8-50%) and faculty representation at symposia (7-34%). Significant gaps in knowledge exist: data from low and middle-income countries, the age distribution and the time taken to enter and complete training. CONCLUSIONS: Despite limited information globally, available data suggest that females are under-represented in training programmes, specialist positions, academic faculty and leadership roles in intensive care. There are significant gaps in data on female participation in the critical care workforce. Further data from intensive care organisations worldwide are required to understand the demographics, challenges and barriers to their professional progress.

Health-related outcomes of critically ill patients with and without sepsis.

PURPOSE: To determine differences in health-related quality of life (HRQoL), survival and healthcare resource use of critically ill adults with and without sepsis. METHODS: We conducted a primary propensity score matched analysis of patients with and without sepsis enrolled in a large multicentre clinical trial. Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and hospital admission and cost of ICU and hospital treatment to 2 years. RESULTS: We obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched 806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After matching, there were no significant differences in the proportion of survivors with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p = 0.86), self-care (24.7% vs. 26.0%, p = 0.44), usual activities (44.5% vs. 46.8%, p = 0.28), pain/discomfort (42.4% vs. 41.6%, p = 0.54) and anxiety/depression (36.9% vs. 37.7%, p = 0.68). There was no significant difference in survival at 2 years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86-1.18, p = 0.94). The initial ICU and hospital admission were longer for patients with sepsis: 10.1 ± 11.9 vs. 8.0 ± 9.8 days (p < 0.0001) and 22.8 ± 21.2 vs. 19.1 ± 19.0 days, (p = 0.0003) respectively. The cost of ICU admissions was higher for patients with sepsis: A$43,345 ± 46,263 (€35,109 ± 35,043) versus 34,844 ± 38,281 (€28,223 ± 31,007), mean difference $8501 (€6885), 95% CI $4342-12,660 (€3517 ± 10,254), p < 0.001 as was the total cost of hospital treatment to 2 years: A$74,120 ± 60,750 (€60,037 ± 49,207) versus A$65,806 ± 59,856 (€53,302 ± 48,483), p = 0.005. CONCLUSIONS: Critically ill patients with sepsis have higher healthcare resource use and costs but similar survival and HRQoL compared to matched patients without sepsis.

Drivers of choice of resuscitation fluid in the intensive care unit: a discrete choice experiment.

OBJECTIVE: To understand the fundamental drivers, and their relative importance, of doctors' and nurses' choice of resuscitation fluid in critically ill patients in Australia and New Zealand. DESIGN: A discrete choice experiment (DCE) administered via an online survey. Respondents were presented with one of four randomly selected DCE choice sets, each including five patient scenarios. The respondent chose between two types of hypothetical resuscitation fluid. The fluid type was characterised by several attributes and each attribute had pre-specified levels. PARTICIPANTS: Convenience sample of 367 Australian and New Zealand intensive care unit doctors and nurses. MAIN OUTCOME MEASURES: The dependent variable was fluid choice, and a regression equation was used to estimate the effect of each fluid attribute on the probability of observing the sequence of choices made over the five patient scenarios. The relative importance of each of the respective fluid attributes was calculated based on the percentage contribution to overall utility (ie, fluid preference). RESULTS: For doctors, safety concerns, patient type and fluid type were collectively responsible for almost three-quarters of decision-making utility (71%). The volume of intravenous fluid administered was the only clinical parameter not reaching statistical significance as a driver of fluid choice (P = 0.06). For nurses, decision making was influenced to a greater extent by the same three attributes (90%), although other unmeasured attributes may have been driving choice. CONCLUSIONS: Doctors and nurses rely on different information when choosing resuscitation fluids, although both cohorts are heavily influenced by safety concerns, patient type and fluid type. This information can be used to modify prescribing behaviour.

Human Albumin Use in Adults in U.S. Academic Medical Centers.

OBJECTIVE: To determine rates and predictors of albumin administration, and estimated costs in hospitalized adults in the United States. DESIGN: Cohort study of adult patients from the University HealthSystem Consortium database from 2009 to 2013. SETTING: One hundred twenty academic medical centers and 299 affiliated hospitals. PATIENTS: A total of 12,366,264 hospitalization records. INTERVENTIONS: Analysis of rates and predictors of albumin administration, and estimated costs. MEASUREMENTS AND MAIN RESULTS: Overall the proportion of admissions during which albumin was administered increased from 6.2% in 2009 to 7.5% in 2013; absolute difference 1.3% (95% CI, 1.30-1.40%; p < 0.0001). The increase was greater in surgical patients from 11.7% in 2009 to 15.1% in 2013; absolute difference 3.4% (95% CI, 3.26-3.46%; p < 0.0001). Albumin use varied geographically being lowest with no increase in hospitals in the North Eastern United States (4.9% in 2009 and 5.3% in 2013) and was more common in bigger (> 750 beds; 5.2% in 2009 and 7.3% in 2013) compared to smaller hospitals (< 250 beds; 4.4% in 2009 to 6.2% in 2013). Factors independently associated with albumin use were appropriate indication for albumin use (odds ratio, 65.220; 95% CI, 62.459-68.103); surgical admission (odds ratio, 7.942; 95% CI, 7.889-7.995); and high severity of illness (odds ratio, 8.933; 95% CI, 8.825-9.042). Total estimated albumin cost significantly increased from $325 million in 2009 to $468 million in 2013; (absolute increase of $233 million), p value less than 0.0001. CONCLUSIONS: The proportion of hospitalized adults in the United States receiving albumin has increased, with marked, and currently unexplained, geographic variability and variability by hospital size.

Hydroxyethyl starch versus saline for resuscitation of patients in intensive care: long-term outcomes and cost-effectiveness analysis of a cohort from CHEST.

BACKGROUND: Hydroxyethyl starch for fluid resuscitation in critically ill patients is not associated with improved short-term patient-centred outcomes compared with crystalloid fluid solutions. However, its effect on longer term health economic outcomes has not been reported. METHODS: We did a prespecified cost-effectiveness analysis of a cohort of patients from New South Wales enrolled in the Crystalloid versus Hydroxyethyl Starch Trial (CHEST), who were randomised to treatment with either 6% hydroxyethyl starch with a molecular weight of 130 kD and a molar substitution ratio of 0·4 or 0·9% sodium chloride (saline) for fluid resuscitation. Clinical outcomes were mortality and life-years gained at 6 months and 24 months, health-related quality of life at 6 months, and quality-adjusted life-years gained at 6 months. Health economic outcomes were hospital and intensive-care unit (ICU) resource use and costs at 24 months and cost-effectiveness, which we defined as the probability of reaching a willingness-to-pay threshold of less than A$50 000 per quality-adjusted life-year gained at 6 months and $100 000 per life-year gained at 24 months. CHEST is registered with ClinicalTrials.gov, number NCT00935168. FINDINGS: 3537 (51%) of 7000 patients were enrolled into CHEST from New South Wales, of whom 3450 (98%) were included in our cost-effectiveness analysis. Mortality at both 6 months and 24 months did not differ between the hydroxyethyl starch and saline groups (6 months: 397/1684 [24%] vs 382/1706 [22%]; relative risk [RR] 1·05, 95% CI 0·93-1·19; p=0·41; 24 months: 586/1687 [35%] vs 594/1708 [35%]; RR 1·00, 95% CI 0·91-1·10; p=0·89). The mean number of life-years gained at 6 months and 24 months was similar between the hydroxyethyl starch and saline groups (6 months: 0·41 days [SD 0·18] vs 0·41 days [0·17]; p=0·25; 24 months: 1·46 years [SD 0·80] vs 1·47 years [0·79]; p=0·72). At 6 months, the mean health-related quality of life score was 0·67 (SD 0·34) with hydroxyethyl starch versus 0·69 (0·35) with saline (p=0·33). The mean number of quality-adjusted life-years gained did not differ between the hydroxyethyl starch and saline groups at 6 months (0·26 days [SD 0·18] vs 0·26 days [0·18]; p=0·33). Total hospital costs (including ICU costs) at 24 months were similar between the hydroxyethyl starch and saline groups (A$62 196 [55 935] vs $62 617 [56 452]; p=0·83). The probability that hydroxyethyl starch was cost effective was 11% at 6 months and 29% at 24 months. INTERPRETATION: Although longer term clinical outcomes did not differ between patients resuscitated with hydroxyethyl starch or saline in the ICU, from a health-care payer's perspective, the probability that hydroxyethyl starch is cost effective in these patients is low. FUNDING: Division of Critical Care and Trauma, George Institute for Global Health.

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.

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.

Triggers for emergency team activation: a multicenter assessment.

PURPOSE: The purpose of the study was to examine triggers for emergency team activation in hospitals with or without a medical emergency team (MET) system. MATERIALS AND METHODS: Within a cluster randomized controlled trial examining the effect of introducing a MET system, we recorded the triggers for emergency team activation. We compared the proportion and rate of such triggers in hospitals with or without a MET system and in relation to type of hospital, type of patient ward, and time of day. RESULTS: In control hospitals, the most common trigger for emergency team activation was a decrease in Glasgow Coma Score by 2 or more points (45.6%), whereas in MET hospitals, it was the fact that staff members were "worried" or the call occurred despite the lack of a "specified reason" (39.3%). In particular, MET hospitals were 35 times more likely to make a call because of staff being "worried" about the patient (14.1% vs 0.4%, P < .001). Control hospitals were also significantly more likely to call an emergency team because of a deteriorating respiratory (P = .003) or pulse (P < .001) rate, more calls had at least 3 triggers for activation (20.8% vs 10.2%, P = .036), and the average number of triggers per call was significantly higher (P = .013). Nonmetropolitan hospitals were more likely to call an emergency team because of respiratory rate abnormalities (33.6% vs 23.2%, P = .015). Coronary care unit calls were more likely to be triggered by abnormalities in pulse rate and systolic blood pressure, and more calls occurred during the period from 6:00 am to noon. CONCLUSIONS: In MET hospitals, more emergency team calls are triggered because staff members are worried about the patient; and fewer calls have multiple triggers. Type of hospital, type of ward, and time of day also affect the nature and frequency of triggers for emergency team activation.

Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data.

BACKGROUND: Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). METHODS: We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation - Survival Using Glucose Algorithm Regulation) study. RESULTS: We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83-1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5-8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44-0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78-1.28; mixed ICU: RR 0.99, 95% CI 0.86-1.12). The different targets of intensive insulin therapy (glucose level < or = 6.1 mmol/L v. < or = 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. INTERPRETATION: Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.

Design, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock.

The role of drotrecogin alfa (activated) (DAA) in severe sepsis remains controversial and clinicians are unsure whether or not to treat their patients with DAA. In response to a request from the European Medicines Agency, Eli Lilly will sponsor a new placebo-controlled trial and history suggests the results will be subject to great scrutiny. An academic steering committee will oversee the conduct of the study and will write the study manuscripts. The steering committee intends that the study will be conducted with the maximum possible transparency; this includes publication of the study protocol and a memorandum of understanding which delineates the role of the sponsor. The trial has the potential to provide clinicians with valuable data but patients will only benefit if clinicians have confidence in the conduct, analysis and reporting of the trial. This special article describes the process by which the trial was developed, major decisions regarding trial design, and plans for independent analysis, interpretation and reporting of the data.

Advancing intensive care research in Australia and New Zealand: development of the binational ANZIC Research Centre.

Over the past 12 years, the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group and the broader intensive care community in Australia and New Zealand have established a track record for conducting high quality, investigator-initiated clinical research in critically ill patients. This is highlighted by the publication of the SAFE (Saline Albumin Fluid Evaluation) study in the New England Journal of Medicine and the MERIT (Medical Early Response Intervention and Therapy) study in the Lancet. Here, we discuss potential impediments to the further advancement of intensive care research in Australia and New Zealand, and suggest strategies to address them. We propose that there is a need to broaden the current research scope and develop more multifaceted research programs that address clinically important issues. We stress the need to also undertake phase II studies to assess safety, pharmacokinetics and biological plausibility of new and established therapies. In addition, we highlight limitations imposed by the relatively small regional population of Australia and New Zealand, and the need to develop international collaborations to allow trials requiring large sample sizes. We contend that the best chance of improving outcomes in many disease states requires studies to commence before patients enter the ICU, which will depend on collaboration with established and emerging craft groups, such as ambulance services, emergency medicine and anaesthesia. We also emphasise the need to study system factors affecting patient outcomes, as well as the translation of research findings into clinical practice. Finally, we describe the establishment and objectives of the Australian and New Zealand Intensive Care Research Centre (ANZIC-RC) and outline the Centre's current projects in the context of an integrated research framework.