Walter T. Linde-Zwirble

Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.

ObjectiveTo determine the incidence, cost, and outcome of severe sepsis in the United States. DesignObservational cohort study. SettingAll nonfederal hospitals (n = 847) in seven U.S. states. PatientsAll patients (n = 192,980) meeting criteria for severe sepsis based on the International Classification of Diseases, Ninth Revision, Clinical Modification. InterventionsNone. Measurements and Main Results We linked all 1995 state hospital discharge records (n = 6,621,559) from seven large states with population and hospital data from the U.S. Census, the Centers for Disease Control, the Health Care Financing Administration, and the American Hospital Association. We defined severe sepsis as documented infection and acute organ dysfunction using criteria based on the International Classification of Diseases, Ninth Revision, Clinical Modification. We validated these criteria against prospective clinical and physiologic criteria in a subset of five hospitals. We generated national age- and gender-adjusted estimates of incidence, cost, and outcome. We identified 192,980 cases, yielding national estimates of 751,000 cases (3.0 cases per 1,000 population and 2.26 cases per 100 hospital discharges), of whom 383,000 (51.1%) received intensive care and an additional 130,000 (17.3%) were ventilated in an intermediate care unit or cared for in a coronary care unit. Incidence increased >100-fold with age (0.2/1,000 in children to 26.2/1,000 in those >85 yrs old). Mortality was 28.6%, or 215,000 deaths nationally, and also increased with age, from 10% in children to 38.4% in those >85 yrs old. Women had lower age-specific incidence and mortality, but the difference in mortality was explained by differences in underlying disease and the site of infection. The average costs per case were

The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis.

22,100, with annual total costs of

Use of intensive care at the end of life in the United States: an epidemiologic study.

16.7 billion nationally. Costs were higher in infants, nonsurvivors, intensive care unit patients, surgical patients, and patients with more organ failure. The incidence was projected to increase by 1.5% per annum. ConclusionsSevere sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction. It is especially common in the elderly and is likely to increase substantially as the U.S. population ages.

Variation in critical care services across North America and Western Europe

Objective: The Surviving Sepsis Campaign (SSC or “the Campaign”) developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations. Design and Setting: A multifaceted intervention to facilitate compliance with selected guideline recommendations in the intensive care unit, emergency department, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the United States, Europe, and South America. Elements of the guidelines were “bundled” into two sets of targets to be completed within 6 hrs and within 24 hrs. An analysis was conducted on data submitted from January 2005 through March 2008. Subjects: A total of 15,022 subjects. Measurements and Main Results: Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 yrs (p < .0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 yrs (p = .008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37% to 30.8% over 2 yrs (p = .001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 yrs (95% confidence interval, 2.5–8.4). Conclusions: The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.

Three-Year Outcomes for Medicare Beneficiaries Who Survive Intensive Care

ObjectiveDespite concern over the appropriateness and quality of care provided in an intensive care unit (ICU) at the end of life, the number of Americans who receive ICU care at the end of life is unknown. We sought to describe the use of ICU care at the end of life in the United States using hospital discharge data from 1999 for six states and the National Death Index. DesignRetrospective analysis of administrative data to calculate age-specific rates of hospitalization with and without ICU use at the end of life, to generate national estimates of end-of-life hospital and ICU use, and to characterize age-specific case mix of ICU decedents. SettingAll nonfederal hospitals in the states of Florida, Massachusetts, New Jersey, New York, Virginia, and Washington. PatientsAll inpatients in nonfederal hospitals in the six states in 1999. InterventionNone. Measurements and Main ResultsWe found that there were 552,157 deaths in the six states in 1999, of which 38.3% occurred in hospital and 22.4% occurred after ICU admission. Using these data to project nationwide estimates, 540,000 people die after ICU admission each year. The age-specific rate of ICU use at the end of life was highest for infants (43%), ranged from 18% to 26% among older children and adults, and fell to 14% for those >85 yrs. Average length of stay and costs were 12.9 days and

Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis

24,541 for terminal ICU hospitalizations and 8.9 days and

The epidemiology of mechanical ventilation use in the United States

8,548 for non-ICU terminal hospitalizations. ConclusionsOne in five Americans die using ICU services. The doubling of persons over the age of 65 yrs by 2030 will require a system-wide expansion in ICU care for dying patients unless the healthcare system pursues rationing, more effective advanced care planning, and augmented capacity to care for dying patients in other settings.

Severe sepsis epidemiology: sampling, selection, and society

Objective:Critical care represents a large percentage of healthcare spending in developed countries. Yet, little is known regarding international variation in critical care services. We sought to understand differences in critical care delivery by comparing data on the distribution of services in eight countries. Design:Retrospective review of existing national administrative data. We identified sources of data in each country to provide information on acute care hospitals and beds, intensive care units and beds, intensive care admissions, and definitions of intensive care beds. Data were all referenced and from as close to 2005 as possible. Setting:United States, France, United Kingdom, Canada, Belgium, Germany, The Netherlands, and Spain. Patients:Not available. Interventions:None. Measurements and Main Results:No standard definition existed for acute care hospital or intensive care unit beds across countries. Hospital beds varied three-fold from 221/100,000 population in the United States to 593/100,000 in Germany. Adult intensive care unit beds also ranged seven-fold from 3.3/100,000 population in the United Kingdom to 24.0/100,000 in Germany. Volume of intensive care unit admissions per year varied ten-fold from 216/100,000 population in the United Kingdom to 2353/100,000 in Germany. The ratio of intensive care unit beds to hospital beds was highly correlated across all countries except the United States (r = .90). There was minimal correlation between the number of intensive care unit beds per capita and health care spending per capita (r = .45), but high inverse correlation between intensive care unit beds and hospital mortality for intensive care unit patients across countries (r = −.82). Conclusions:Absolute critical care services vary dramatically between countries with wide differences in both numbers of beds and volume of admissions. The number of intensive care unit beds per capita is not strongly correlated with overall health expenditure, but does correlate strongly with mortality. These findings demonstrate the need for critical care data from all countries, as they are essential for interpretation of studies, and policy decisions regarding critical care services.

Trends in the epidemiology of pediatric severe sepsis

CONTEXT Although hospital mortality has decreased over time in the United States for patients who receive intensive care, little is known about subsequent outcomes for those discharged alive. OBJECTIVE To assess 3-year outcomes for Medicare beneficiaries who survive intensive care. DESIGN, SETTING, AND PATIENTS A matched, retrospective cohort study was conducted using a 5% sample of Medicare beneficiaries older than 65 years. A random half of all patients were selected who received intensive care and survived to hospital discharge in 2003 with 3-year follow-up through 2006. From the other half of the sample, 2 matched control groups were generated: hospitalized patients who survived to discharge (hospital controls) and the general population (general controls), individually matched on age, sex, race, and whether they had surgery (for hospital controls). MAIN OUTCOME MEASURE Three-year mortality after hospital discharge. RESULTS There were 35,308 intensive care unit (ICU) patients who survived to hospital discharge. The ICU survivors had a higher 3-year mortality (39.5%; n = 13,950) than hospital controls (34.5%; n = 12,173) (adjusted hazard ratio [AHR], 1.07 [95% confidence interval {CI}, 1.04-1.10]; P < .001) and general controls (14.9%; n = 5266) (AHR, 2.39 [95% CI, 2.31-2.48]; P < .001). The ICU survivors who did not receive mechanical ventilation had minimal increased risk compared with hospital controls (3-year mortality, 38.3% [n = 12,716] vs 34.6% [n=11,470], respectively; AHR, 1.04 [95% CI, 1.02-1.07]). Those receiving mechanical ventilation had substantially increased mortality (57.6% [1234 ICU survivors] vs 32.8% [703 hospital controls]; AHR, 1.56 [95% CI, 1.40-1.73]), with risk concentrated in the 6 months after the quarter of hospital discharge (6-month mortality, 30.1% (n = 645) for those receiving mechanical ventilation vs 9.6% (n = 206) for hospital controls; AHR, 2.26 [95% CI, 1.90-2.69]). Discharge to a skilled care facility for ICU survivors (33.0%; n = 11,634) and hospital controls (26.4%; n = 9328) also was associated with high 6-month mortality (24.1% for ICU survivors and hospital controls discharged to a skilled care facility vs 7.5% for ICU survivors and hospital controls discharged home; AHR, 2.62 [95% CI, 2.50-2.74]; P < .001 for ICU survivors and hospital controls combined). CONCLUSIONS There is a large US population of elderly individuals who survived the ICU stay to hospital discharge but who have a high mortality over the subsequent years in excess of that seen in comparable controls. The risk is concentrated early after hospital discharge among those who require mechanical ventilation.

Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis

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