Lisa A. Weissfeld

A Randomized Trial of Protocol-Based Care for Early Septic Shock

BACKGROUND In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary. METHODS In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support. RESULTS We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval [CI], 0.82 to 1.31; P=0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support. CONCLUSIONS In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.).

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

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

Survival after liver transplantation in the United States: a disease-specific analysis of the UNOS database.

24,541 for terminal ICU hospitalizations and 8.9 days and

Amyloid Imaging in Mild Cognitive Impairment Subtypes

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.

Increased Dopamine D2/D3 Receptor Binding After Recovery from Anorexia Nervosa Measured by Positron Emission Tomography and [11C]Raclopride

Our goal was to describe disease‐specific survival and the clinical variables that predict survival in a large national cohort of adult liver transplant recipients. Data on 17,044 adult patients who received an initial orthotopic liver transplant between 1990 and 1996 with follow‐up through 1999 was obtained from the United Network for Organ Sharing (UNOS). Disease‐specific Kaplan‐Meier survival plots and Cox Proportional Hazards models were estimated, and differences in the clinical characteristics of patients at the time of transplantation by disease were examined. Overall posttransplant survival currently exceeds 85% in the first year and is approaching 75% at 5 years. Unadjusted Kaplan‐Meier survival is improved for recipients who are younger, female, and in better clinical condition. Survival is a function of disease and level of illness: cancer, fulminant liver failure, alcoholic liver disease, and the hepatitidies have the poorest prognosis, while primary billiary cirrohsis and sclerosing cholangitis have the best. Recipients who were outpatients before transplantation have longer survival than those transplanted from the hospital or intensive care unit. Although the model for end‐stage liver disease (MELD) score was designed to predict pretransplant survival, patients with higher MELD scores have poorer posttransplant survival, but the MELD score is less predictive than the specific disease. Differences in disease‐specific survival are partially explained by differences in disease severity at the time of transplantation. In conclusion, Disease‐specific survival models indicate that there remains tremendous variability in survival as a function of underlying liver disease. However, a significant portion of the difference in survival between diseases arises from differences in clinical characteristics at the time of transplantation. (Liver Transpl 2004;10:886–897.)

Inflammatory Markers at Hospital Discharge Predict Subsequent Mortality after Pneumonia and Sepsis

We utilized the amyloid imaging ligand Pittsburgh Compound B (PiB) to determine the presence of Alzheimers disease (AD) pathology in different mild cognitive impairment (MCI) subtypes and to relate increased PiB binding to other markers of early AD and longitudinal outcome.

End-of-life care for the critically ill: A national intensive care unit survey.

BACKGROUND Several lines of evidence support the possibility that disturbances of dopamine (DA) function could contribute to alterations of weight, feeding, motor activity, and reward in anorexia nervosa (AN). METHODS To assess possibly trait-related disturbances but avoid confounding effects of malnutrition, 10 women who were recovered from AN (REC AN) were compared with 12 healthy control women (CW). Positron emission tomography with [(11)C]raclopride was used to assess DA D2/D3 receptor binding. RESULTS The women who were recovered from AN had significantly higher [(11)C]raclopride binding potential in the antero-ventral striatum than CW. For REC AN, [(11)C]raclopride binding potential was positively related to harm avoidance in the dorsal caudate and dorsal putamen. CONCLUSIONS These data lend support for the possibility that decreased intrasynaptic DA concentration or increased D2/D3 receptor density or affinity is associated with AN and might contribute to the characteristic harm avoidance or increased physical activity found in AN. Most intriguing is the possibility that individuals with AN might have a DA related disturbance of reward mechanisms contributing to altered hedonics of feeding behavior and their ascetic, anhedonic temperament.

Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia

RATIONALE Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown. OBJECTIVES To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes. METHODS Prospective cohort study at 28 sites. MEASUREMENTS AND MAIN RESULTS We used standard criteria to define CAP and the National Death Index to determine all-cause and cause-specific 1-year mortality. At hospital discharge, 1,799 subjects (77.5%) were alive and vital signs had returned to normal in 1,512 (87%) subjects. The geometric means (+/-SD) for circulating IL-6 and IL-10 concentrations were 6.9 (+/-1) pg/ml and 1.2 (+/-1.1) pg/ml. At 1 year, 307 (17.1%) subjects had died. Higher IL-6 and IL-10 concentrations at hospital discharge were associated with an increased risk of death, which gradually fell over time. Using Grays survival model, the associations were independent of demographics, comorbidities, and severity of illness (for each log-unit increase, the range of adjusted hazard ratios [HRs] for IL-6 were 1.02-1.46, P < 0.0001, and for IL-10 were 1.17-1.44, P = 0.01). The ranges of HRs for each log-unit increase in IL-6 and IL-10 concentrations among subjects who did and did not develop severe sepsis were 0.95-1.27 and 1.07-1.55, respectively. High IL-6 concentrations were associated with death due to cardiovascular disease, cancer, infections, and renal failure (P = 0.008). CONCLUSIONS Despite clinical recovery, many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death.

Intensive care unit safety culture and outcomes: a US multicenter study

Objective:One in five Americans dies following treatment in an intensive care unit (ICU), and evidence indicates the need to improve end-of-life care for ICU patients. We conducted this study to elicit the views and experiences of ICU directors regarding barriers to optimal end-of-life care and to identify the type, availability, and perceived benefit of specific strategies that may improve this care. Design:Self-administered mail survey. Setting:Six hundred intensive care units. Participants:A random, nationally representative sample of nursing and physician directors of 600 adult ICUs in the United States. Interventions:Mail survey. Measurements and Main Results:We asked participants about barriers to end-of-life care (1 = huge to 5 = not at all a barrier), perceived benefit of strategies to improve end-of-life care, and availability of these strategies. From 468 ICUs (78.0% of sample), 590 ICU directors participated (406 nurses [65.1% response] and 184 physicians [31.7% response]). Respondents had a mean of 16.6 yrs (sd 7.6 yrs) of ICU experience. Important barriers to better end-of-life care included patient/family factors, including unrealistic patient/family expectations 2.5 (1.0), inability of patients to participate in discussions 2.7 (0.9), and lack of advance directives 2.9 (1.0); clinician factors, which included insufficient physician training in communication 2.9 (1.1) and competing demands on physicians’ time 3.0 (1.1); and institution/ICU factors, such as suboptimal space for family meetings 3.5 (1.2) and lack of a palliative care service 3.4 (1.2). More than 80% of respondents rated 14 of 14 strategies as likely to improve end-of-life care, including trainee role modeling by experienced clinicians, clinician training in communication and symptom management, regular meetings of senior clinicians with families, bereavement programs, and end-of-life care quality monitoring. However, few of these strategies were widely available. Conclusions:Intensive care unit directors perceive important barriers to optimal end-of-life care but also universally endorse many practical strategies for quality improvement. LEARNING OBJECTIVESOn completion of this article, the reader should be able to: Describe barriers to improved end-of-life care in the intensive care unit. List strategies that are likely to improve end-of-life care. Use this information in the clinical setting. All authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to this educational activity. Lippincott CME Institute, Inc., has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit.

Serotonin 1A receptor binding and treatment response in late-life depression.

STUDY OBJECTIVE The Pneumonia Severity Index and CURB-65 predict outcomes in community-acquired pneumonia but have limitations. Procalcitonin, a biomarker of bacterial infection, may provide prognostic information in community-acquired pneumonia. Our objective is to describe the pattern of procalcitonin in community-acquired pneumonia and determine whether procalcitonin provides prognostic information beyond the Pneumonia Severity Index and CURB-65. METHODS We conducted a multicenter prospective cohort study in 28 community and teaching emergency departments. Patients presenting with a clinical and radiographic diagnosis of community-acquired pneumonia were enrolled. We stratified procalcitonin levels a priori into 4 tiers: I: less than 0.1; II: greater than 0.1 to less than 0.25; III: greater than 0.25 to less than 0.5; and IV: greater than 0.5 ng/mL. Primary outcome was 30-day mortality. RESULTS One thousand six hundred fifty-one patients formed the study cohort. Procalcitonin levels were broadly spread across tiers: 32.8% (I), 21.6% (II), 10.2% (III), and 35.4% (IV). Used alone, procalcitonin had modest test characteristics: specificity (35%), sensitivity (92%), positive likelihood ratio (1.41), and negative likelihood ratio (0.22). Adding procalcitonin to the Pneumonia Severity Index in all subjects minimally improved performance. Adding procalcitonin to low-risk Pneumonia Severity Index subjects (classes I to III) provided no additional information. However, subjects in procalcitonin tier I had low 30-day mortality, regardless of clinical risk, including those in higher risk classes (1.5% versus 1.6% for those in Pneumonia Severity Index classes I to III versus classes IV/V). Among high-risk Pneumonia Severity Index subjects (classes IV/V), one quarter (126/546) were in procalcitonin tier I, and the negative likelihood ratio of procalcitonin tier I was 0.09. Procalcitonin tier I was also associated with lower burden of other adverse outcomes. Similar results were observed with CURB-65 stratification. CONCLUSION Selective use of procalcitonin as an adjunct to existing rules may offer additional prognostic information in high-risk patients.