David J. Murphy

Inhaled Corticosteroids in Patients With Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis

CONTEXT Recent studies of inhaled corticosteroid (ICS) therapy for managing stable chronic obstructive pulmonary disease (COPD) have yielded conflicting results regarding survival and risk of adverse events. OBJECTIVE To systematically review and quantitatively synthesize the effects of ICS therapy on mortality and adverse events in patients with stable COPD. DATA SOURCES Search of MEDLINE, CENTRAL, EMBASE, CINAHL, Web of Science, and PsychInfo through February 9, 2008. STUDY SELECTION Eligible studies were double-blind, randomized controlled trials comparing ICS therapy for 6 or more months with nonsteroid inhaled therapy in patients with COPD. DATA EXTRACTION Two authors independently abstracted data including study characteristics, all-cause mortality, pneumonia, and bone fractures. The I(2) statistic was used to assess heterogeneity. Study-level data were pooled using a random-effects model (when I(2) > or = 50%) or a fixed-effects model (when I(2) < 50%). For the primary outcome of all-cause mortality at 1 year, our meta-analysis was powered to detect a 1.0% absolute difference in mortality, assuming a 2-sided alpha of .05 and power of 0.80. RESULTS Eleven eligible randomized controlled trials (14,426 participants) were included. In trials with mortality data, no difference was observed in 1-year all-cause mortality (128 deaths among 4636 patients in the treatment group and 148 deaths among 4597 patients in the control group; relative risk [RR], 0.86; 95% confidence interval [CI], 0.68-1.09; P = .20; I(2) = 0%). In the trials with data on pneumonia, ICS therapy was associated with a significantly higher incidence of pneumonia (777 cases among 5405 patients in the treatment group and 561 cases among 5371 patients in the control group; RR, 1.34; 95% CI, 1.03-1.75; P = .03; I(2) = 72%). Subgroup analyses indicated an increased risk of pneumonia in the following subgroups: highest ICS dose (RR, 1.46; 95% CI, 1.10-1.92; P = .008; I(2) = 78%), shorter duration of ICS use (RR, 2.12; 95% CI, 1.47-3.05; P < .001; I(2) = 0%), lowest baseline forced expiratory volume in the first second of expiration (RR, 1.90; 95% CI, 1.26-2.85; P = .002; I(2) = 0%), and combined ICS and bronchodilator therapy (RR, 1.57; 95% CI, 1.35-1.82; P < .001; I(2) = 24%). CONCLUSIONS Among patients with COPD, ICS therapy does not affect 1-year all-cause mortality. ICS therapy is associated with a higher risk of pneumonia. Future studies should determine whether specific subsets of patients with COPD benefit from ICS therapy.

Using evidence, rigorous measurement, and collaboration to eliminate central catheter-associated bloodstream infections.

Healthcare-associated infections are common, costly, and often lethal. Although there is growing pressure to reduce these infections, one project thus far has unprecedented collaboration among many groups at every level of health care. After this project produced a 66% reduction in central catheter-associated bloodstream infections and a median central catheter-associated bloodstream infection rate of zero across >100 intensive care units in Michigan, the Agency for Healthcare Research and Quality awarded a grant to spread this project to ten additional states. A program, called On the CUSP: Stop BSI, was formulated from the Michigan project, and additional funding from the Agency for Healthcare Research and Quality and private philanthropy has positioned the program for implementation state by state across the United States. Furthermore, the program is being implemented throughout Spain and England and is undergoing pilot testing in several hospitals in Peru. The model in this program balances the tension between being scientifically rigorous and feasible. The three main components of the model include translating evidence into practice at the bedside to prevent central catheter-associated bloodstream infections, improving culture and teamwork, and having a data collection system to monitor central catheter-associated bloodstream infections and other variables. If successful, this program will be the first national quality improvement program in the United States with quantifiable and measurable goals.

Structure, process, and annual ICU mortality across 69 centers: United States critical illness and injury trials group critical illness outcomes study

Objective:Hospital-level variations in structure and process may affect clinical outcomes in ICUs. We sought to characterize the organizational structure, processes of care, use of protocols, and standardized outcomes in a large sample of U.S. ICUs. Design:We surveyed 69 ICUs about organization, size, volume, staffing, processes of care, use of protocols, and annual ICU mortality. Setting:ICUs participating in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. Subjects:Sixty-nine intensivists completed the survey. Measurements and Main Results:We characterized structure and process variables across ICUs, investigated relationships between these variables and annual ICU mortality, and adjusted for illness severity using Acute Physiology and Chronic Health Evaluation II. Ninety-four ICU directors were invited to participate in the study and 69 ICUs (73%) were enrolled, of which 25 (36%) were medical, 24 (35%) were surgical, and 20 (29%) were of mixed type, and 64 (93%) were located in teaching hospitals with a median number of five trainees per ICU. Average annual ICU mortality was 10.8%, average Acute Physiology and Chronic Health Evaluation II score was 19.3, 58% were closed units, and 41% had a 24-hour in-house intensivist. In multivariable linear regression adjusted for Acute Physiology and Chronic Health Evaluation II and multiple ICU structure and process factors, annual ICU mortality was lower in surgical ICUs than in medical ICUs (5.6% lower [95% CI, 2.4–8.8%]) or mixed ICUs (4.5% lower [95% CI, 0.4–8.7%]). We also found a lower annual ICU mortality among ICUs that had a daily plan of care review (5.8% lower [95% CI, 1.6–10.0%]) and a lower bed-to-nurse ratio (1.8% lower when the ratio decreased from 2:1 to 1.5:1 [95% CI, 0.25–3.4%]). In contrast, 24-hour intensivist coverage (p = 0.89) and closed ICU status (p = 0.16) were not associated with a lower annual ICU mortality. Conclusions:In a sample of 69 ICUs, a daily plan of care review and a lower bed-to-nurse ratio were both associated with a lower annual ICU mortality. In contrast to 24-hour intensivist staffing, improvement in team communication is a low-cost, process-targeted intervention strategy that may improve clinical outcomes in ICU patients.

Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009-2014

Importance Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, −2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (−3.3%/y [95% CI, −5.6% to −1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (−1.3%/y [95% CI, −3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (−7.0%/y [95% CI, −8.8% to −5.2%], P < .001), as did death or discharge to hospice (−4.5%/y [95% CI, −6.1% to −2.8%], P < .001). Clinical criteria were more sensitive in identifying sepsis than claims (69.7% [95% CI, 52.9% to 92.0%] vs 32.3% [95% CI, 24.4% to 43.0%], P < .001), with comparable positive predictive value (70.4% [95% CI, 64.0% to 76.8%] vs 75.2% [95% CI, 69.8% to 80.6%], P = .23). Conclusions and Relevance In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.

A Practical Tool to Identify and Eliminate Barriers to Compliance with Evidence-Based Guidelines

A practical tool provides an interdisciplinary approach to identify barriers to guideline compliance and implement actions to eliminate or mitigate the effect of the barriers.

Transfusion practice in the intensive care unit: a 10-year analysis

BACKGROUND: Clinical guidelines recommend a restrictive transfusion strategy in nonhemorrhaging critically ill patients.

Protocols and hospital mortality in critically ill patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study

Objective:Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs. Design:Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week. Patients:A total of 6,179 critically ill patients. Setting:Fifty-nine ICUs in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. Interventions:None. Measurements and Main Results:The primary exposure was the number of ICU protocols; the primary outcome was hospital mortality. A total of 5,809 participants were followed prospectively, and 5,454 patients in 57 ICUs had complete outcome data. The median number of protocols per ICU was 19 (interquartile range, 15–21.5). In single-variable analyses, there were no differences in ICU and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in ICUs with a high versus low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p = 0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between ICUs with high versus low numbers of protocols for lung protective ventilation in acute respiratory distress syndrome (47% vs 52%; p = 0.28) and for spontaneous breathing trials (55% vs 51%; p = 0.27). Conclusions:Clinical protocols are highly prevalent in U.S. ICUs. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality.

How to avoid fluid overload.

Purpose of reviewThis review highlights the recent evidence describing the outcomes associated with fluid overload in critically ill patients and provides an overview of fluid management strategies aimed at preventing fluid overload during the resuscitation of patients with shock. Recent findingsFluid overload is a common complication of fluid resuscitation and is associated with increased hospital costs, morbidity and mortality. SummaryFluid management goals differ during the resuscitation, optimization, stabilization and evacuation phases of fluid resuscitation. To prevent fluid overload, strategies that reduce excessive fluid infusions and emphasize the removal of accumulated fluids should be implemented.

Red Blood Cell Transfusion Practices in Acute Lung Injury: What do patient factors contribute?

Objective:To describe red blood cell (RBC) transfusion practices and evaluate the association between patient-related factors and pretransfusion hemoglobin concentration in acute lung injury (ALI). Design:Secondary analysis of prospectively collected data. Setting:Nine intensive care units (ICUs) in three teaching hospitals in Baltimore, MD. Patients:Two hundred forty-nine consecutive patients with ALI requiring mechanical ventilation. Interventions:None. Measurements and Main Results:Simple and multiple linear regression analyses were used to evaluate the association between the nadir hemoglobin concentration on the day of initial RBC transfusion and 20 patient-level demographic, clinical and ICU treatment factors as well as ICU type. Of 249 patients with ALI, 47% received an RBC transfusion in the ICU without evidence of active hemorrhage or acute cardiac ischemia. The mean (sd) nadir hemoglobin on the day of first transfusion was 7.7 (1.1) g/dL with 67%, 36%, 15%, and 5% of patients transfused at >7, >8, >9, and >10g/dL, respectively. Transfused patients received a mean (sd) of 5 (6) RBC units from ALI diagnosis to ICU discharge. Prehospital use of iron or erythropoietin and platelet transfusion in the ICU were independently associated with lower pretransfusion hemoglobin concentrations. No patient factors were associated with higher hemoglobin concentrations. Admission to a surgical (vs. medical) ICU was independently associated with a 0.6 g/dL (95% confidence interval 0.1–1.1 g/dL) higher pretransfusion hemoglobin. Conclusions:Patients with ALI commonly receive RBC transfusions in the ICU. The pretransfusion hemoglobin observed in our study was lower than earlier studies, but a restrictive strategy was not universally adopted. Patient factors do not explain the gap between clinical trial evidence and routine transfusion practices. Future studies should further explore ICU- and physician-related factors as a source of variability in transfusion practice.

Red blood cell transfusion practices in two surgical intensive care units: a mixed methods assessment of barriers to evidence-based practice.

Despite evidence supporting restrictive red blood cell (RBC) transfusion thresholds and the associated clinical practice guidelines, clinical practice has been slow to change in the intensive care unit (ICU). Our aim was to identify barriers to conservative transfusion practice adherence.