Allan J. Walkey

Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis*.

Objectives:Trends in severe sepsis mortality derived from administrative data may be biased by changing International Classification of Diseases, 9th Revision, Clinical Modification, coding practices. We sought to determine temporal trends in severe sepsis mortality using clinical trial data that does not rely on International Classification of Diseases, 9th Revision, Clinical Modifications coding and compare mortality trends in trial data with those observed from administrative data. Design:We searched MEDLINE for multicenter randomized trials that enrolled patients with severe sepsis from 1991 to 2009. We calculated standardized mortality ratios for each trial from observed 28-day mortality of usual care participants and predicted mortality from severity-of-illness scores. To compare mortality trends from clinical trials to administrative data, we identified adult severe sepsis hospitalizations in the Nationwide Inpatient Sample, 1993–2009, using two previously validated algorithms. Setting:In-patient. Patients:Patients with severe sepsis or septic shock. Interventions:None. Measurements and Main Results:Of 3,244 potentially eligible articles, we included 36 multicenter severe sepsis trials, with a total of 14,418 participants in a usual care arm. Participants with severe sepsis receiving usual care had a 28-day mortality of 33.2%. Observed mortality decreased 3.0% annually (95% CI, 0.8%–5.0%; p = 0.009), decreasing from 46.9% (standardized mortality ratio 0.94; 95% CI, 0.86–1.03) during years 1991–1995 to 29% (standardized mortality ratio 0.53; 95% CI, 0.50–0.57) during years 2006–2009 (3.0% annual change). Trends in hospital mortality among patients with severe sepsis identified from administrative data (Angus definition, 4.7% annual change; 95% CI, 4.1%–5.3%; p = 0.69 and Martin definition, 3.5% annual change; 95% CI, 3.0%–4.1%; p = 0.97) were similar to trends identified from clinical trials. Conclusion:Since 1991, patients with severe sepsis enrolled in usual care arms of multicenter randomized trials have experienced decreasing mortality. The mortality trends identified in clinical trial participants appear similar to those identified using administrative data and support the use of administrative data to monitor mortality trends in patients with severe sepsis.

Severe Sepsis in Pre-Hospital Emergency Care: Analysis of Incidence, Care, and Outcome

RATIONALE Severe sepsis is common and highly morbid, yet the epidemiology of severe sepsis at the frontier of the health care system-pre-hospital emergency care-is unknown. OBJECTIVES We examined the epidemiology of pre-hospital severe sepsis among emergency medical services (EMS) encounters, relative to acute myocardial infarction and stroke. METHODS Retrospective study using a community-based cohort of all nonarrest, nontrauma King County EMS encounters from 2000 to 2009 who were transported to a hospital. MEASUREMENTS AND MAIN RESULTS Overall incidence rate of hospitalization with severe sepsis among EMS encounters, as well as pre-hospital characteristics, admission diagnosis, and outcomes. Among 407,176 EMS encounters, we identified 13,249 hospitalizations for severe sepsis, of whom 2,596 died in the hospital (19.6%). The crude incidence rate of severe sepsis was 3.3 per 100 EMS encounters, greater than for acute myocardial infarction or stroke (2.3 per 100 and 2.2 per 100 EMS encounters, respectively). More than 40% of all severe sepsis hospitalizations arrived at the emergency department after EMS transport, and 80% of cases were diagnosed on admission. Pre-hospital care intervals, on average, exceeded 45 minutes for those hospitalized with severe sepsis. One-half or fewer of patients with severe sepsis were transported by paramedics (n = 7,114; 54%) or received pre-hospital intravenous access (n = 4,842; 37%). CONCLUSIONS EMS personnel care for a substantial and increasing number of patients with severe sepsis, and spend considerable time on scene and during transport. Given the emphasis on rapid diagnosis and intervention for sepsis, the pre-hospital interval may represent an important opportunity for recognition and care of sepsis.

Linezolid vs Glycopeptide Antibiotics for the Treatment of Suspected Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Meta-analysis of Randomized Controlled Trials

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial pneumonia. Societal guidelines suggest linezolid may be the preferred treatment of MRSA nosocomial pneumonia. We investigated the efficacy of linezolid compared with glycopeptide antibiotics (vancomycin or teicoplanin) for nosocomial pneumonia. METHODS This was a systematic review and meta-analysis of English language, randomized, controlled trials comparing linezolid to glycopeptide antibiotics for suspected MRSA pneumonia in subjects > 12 years of age. A highly sensitive search of PubMed MEDLINE and Cochrane Central Register of Controlled Trials databases identified relevant studies. RESULTS Eight trials encompassing 1,641 subjects met entry criteria. Linezolid was not superior to glycopeptide antibiotics for end points of clinical success (relative risk [RR] linezolid vs glycopeptide, 1.04; 95% CI, 0.97-1.11; P = .28), microbiologic success (RR, 1.13; 95% CI, 0.97-1.31; P = .12), or mortality (RR, 0.91; 95% CI, 0.69-1.18; P = .47). In addition, clinical success in the subgroup of subjects with MRSA-positive respiratory tract culture (RR, 1.23; 95% CI, 0.97-1.57; P = .09) was not significantly different from those without MRSA (RR, 0.95; 95% CI, 0.83-1.09; P = .48), P for interaction, 0.07. The risk for adverse events was not different between the two antibiotic classes (RR, 0.96; 95% CI, 0.86-1.07; P = .48). CONCLUSION Randomized controlled trials do not support superiority of linezolid over glycopeptide antibiotics for the treatment of nosocomial pneumonia. We recommend that decisions between linezolid or glycopeptide antibiotics for empirical or MRSA-directed therapy of nosocomial pneumonia depend on local availability, antibiotic resistance patterns, preferred routes of delivery, and cost, rather than presumed differences in efficacy.

Outcomes of Medicare Beneficiaries Undergoing Catheter Ablation for Atrial Fibrillation

Background— Atrial fibrillation is common among older persons. Catheter ablation is increasingly used in patients for whom medical therapy has failed. Methods and Results— We conducted a retrospective cohort study of all fee-for-service Medicare beneficiaries ≥65 years of age who underwent catheter ablation for atrial fibrillation between July 1, 2007, and December 31, 2009. The main outcome measures were major complications within 30 days and mortality, heart failure, stroke, hospitalization, and repeat ablation within 1 year. A total of 15 423 patients underwent catheter ablation for atrial fibrillation. Mean age was 72 years; 41% were women; and >95% were white. For every 1000 procedures, there were 17 cases of hemopericardium requiring intervention, 8 cases of stroke, and 8 deaths within 30 days. More than 40% of patients required hospitalization within 1 year; however, atrial fibrillation or flutter was the primary discharge diagnosis in only 38.4% of cases. Eleven percent of patients underwent repeat ablation within 1 year. Renal impairment (hazard ratio, 2.07; 95% confidence interval, 1.66–2.58), age ≥80 years (hazard ratio, 3.09; 95% confidence interval, 2.32–4.11), and heart failure (hazard ratio, 2.54; 95% confidence interval, 2.07–3.13) were major risk factors for 1-year mortality. Advanced age was a major risk factor for all adverse outcomes. Conclusions— Major complications after catheter ablation for atrial fibrillation were associated with advanced age but were fairly infrequent. Few patients underwent repeat ablation. Randomized trials are needed to inform risk-benefit calculations for older persons with drug-refractory, symptomatic atrial fibrillation.

An official American Thoracic Society/European Society of intensive care medicine/society of critical care medicine clinical practice guideline: Mechanical ventilation in adult patients with acute respiratory distress syndrome

Background: This document provides evidence‐based clinical practice guidelines on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS). Methods: A multidisciplinary panel conducted systematic reviews and metaanalyses of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. Results: For all patients with ARDS, the recommendation is strong for mechanical ventilation using lower tidal volumes (4‐8 ml/kg predicted body weight) and lower inspiratory pressures (plateau pressure < 30 cm H2O) (moderate confidence in effect estimates). For patients with severe ARDS, the recommendation is strong for prone positioning for more than 12 h/d (moderate confidence in effect estimates). For patients with moderate or severe ARDS, the recommendation is strong against routine use of high‐frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positive end‐expiratory pressure (moderate confidence in effect estimates) and recruitment maneuvers (low confidence in effect estimates). Additional evidence is necessary to make a definitive recommendation for or against the use of extracorporeal membrane oxygenation in patients with severe ARDS. Conclusions: The panel formulated and provided the rationale for recommendations on selected ventilatory interventions for adult patients with ARDS. Clinicians managing patients with ARDS should personalize decisions for their patients, particularly regarding the conditional recommendations in this guideline.

Long-term Outcomes Following Development of New-Onset Atrial Fibrillation During Sepsis

BACKGROUND New-onset atrial fibrillation (AF) is associated with adverse outcomes during a sepsis hospitalization; however, long-term outcomes following hospitalization with sepsis-associated new-onset AF are unclear. METHODS We used a Medicare 5% sample to identify patients who survived hospitalization with sepsis between 1999 and 2010. AF status was defined as no AF, prior AF, or new-onset AF based on AF claims during and prior to a sepsis hospitalization. We used competing risk models to determine 5-year risks of AF occurrence, heart failure, ischemic stroke, and mortality after the sepsis hospitalization, according to AF status during the sepsis admission. RESULTS We identified 138,722 sepsis survivors, of whom 95,536 (69%) had no AF during sepsis, 33,646 (24%) had prior AF, and 9,540 (7%) had new-onset AF during sepsis. AF occurrence following sepsis hospitalization was more common among patients with new-onset AF during sepsis (54.9%) than in patients with no AF during sepsis (15.5%). Compared with patients with no AF during sepsis, those with new-onset AF during sepsis had greater 5-year risks of hospitalization for heart failure (11.2% vs 8.2%; multivariable-adjusted hazard ratio [HR], 1.25; 95% CI, 1.16-1.34), ischemic stroke (5.3% vs 4.7%; HR, 1.22; 95% CI, 1.10-1.36), and death (74.8% vs 72.1%; HR, 1.04; 95% CI,1.01-1.07). CONCLUSIONS Most sepsis survivors with new-onset AF during sepsis have AF occur after discharge from the sepsis hospitalization and have increased long-term risks of heart failure, ischemic stroke, and death. Our findings may have implications for posthospitalization surveillance of patients with new-onset AF during a sepsis hospitalization.

Use of Noninvasive Ventilation in Patients with Acute Respiratory Failure, 2000–2009: A Population-Based Study

RATIONALE Although evidence supporting use of noninvasive ventilation (NIV) during acute exacerbations of chronic obstructive pulmonary disease (COPD) is strong, evidence varies widely for other causes of acute respiratory failure. OBJECTIVES To compare utilization trends and outcomes associated with NIV in patients with and without COPD. METHODS We identified 11,659,668 cases of acute respiratory failure from the Nationwide Inpatient Sample during years 2000 to 2009 and compared NIV utilization trends and failure rates for cases with or without a diagnosis of COPD. MEASUREMENTS AND MAIN RESULTS The proportion of patients with COPD who received NIV increased from 3.5% in 2000 to 12.3% in 2009 (250% increase), and the proportion of patients without COPD who received NIV increased from 1.2% in 2000 to 6.0% in 2009 (400% increase). The rate of increase in the use of NIV was significantly greater for patients without COPD (18.1% annual change) than for patients with COPD (14.3% annual change; P = 0.02). Patients without COPD were more likely to have failure of NIV requiring endotracheal intubation (adjusted odds ratio, 1.19; 95% confidence interval, 1.15-1.22; P < 0.0001). Patients in whom NIV failed had higher hospital mortality than patients receiving mechanical ventilation without a preceding trial of NIV (adjusted odds ratio, 1.14; 95% confidence interval, 1.11-1.17; P < 0.0001). CONCLUSION The use of NIV during acute respiratory failure has increased at a similar rate for all diagnoses, regardless of supporting evidence. However, NIV is more likely to fail in patients without COPD, and NIV failure is associated with increased mortality.

Acute respiratory distress syndrome: epidemiology and management approaches

Acute lung injury and the more severe acute respiratory distress syndrome represent a spectrum of lung disease characterized by the sudden onset of inflammatory pulmonary edema secondary to myriad local or systemic insults. The present article provides a review of current evidence in the epidemiology and treatment of acute lung injury and acute respiratory distress syndrome, with a focus on significant knowledge gaps that may be addressed through epidemiologic methods.

Clinical course of atrial fibrillation in older adults: the importance of cardiovascular events beyond stroke

AIMS Atrial fibrillation increases the risks of stroke, heart failure, and death, and anticoagulation therapy increases the risk of gastrointestinal haemorrhage. However, the relative event rates for these outcomes are not well described. We sought to define the risks of major clinical events in older adults after a new diagnosis of atrial fibrillation. METHODS AND RESULTS We undertook a population-based, retrospective cohort study of a nationally representative sample of fee-for-service Medicare beneficiaries 65 years or older with incident atrial fibrillation diagnosed between 1999 and 2007. The main outcome measures were mortality and hospitalization or emergency department care for heart failure, myocardial infarction, stroke, or gastrointestinal haemorrhage. Among 186 461 patients with atrial fibrillation and no recent hospitalizations for heart failure, myocardial infarction, stroke, or gastrointestinal haemorrhage, mortality was the most frequent of these major clinical events (19.5% at 1 year; 48.8% at 5 years). By 5 years, 13.7% of patients were hospitalized for heart failure, 7.1% developed new-onset stroke, and 5.7% had gastrointestinal haemorrhage. Myocardial infarction was less frequent (3.9% at 5 years). Rates of mortality, heart failure, myocardial infarction, stroke, and gastrointestinal bleeding increased with older age and higher CHADS2 scores. Among 44 479 patients with previous events, the 5-year risk of death was greatest among patients with recent bleeding events (70.1%) and stroke (63.7%) and lowest among those with recent myocardial infarction (54.9%). CONCLUSION After the diagnosis of incident atrial fibrillation in older adults, mortality was the most frequent major outcome during the first 5 years. Among non-fatal cardiovascular events, heart failure was the most common event.

Utilization patterns and outcomes associated with central venous catheter in septic shock: a population-based study.

Objectives:In 2001, a randomized trial showed decreased mortality with early, goal-directed therapy in septic shock, a strategy later recommended by the Surviving Sepsis Campaign. Placement of a central venous catheter is necessary to administer goal-directed therapy. We sought to evaluate nationwide trends in: 1) central venous catheter utilization and 2) the association between early central venous catheter insertion and mortality in patients with septic shock. Design:We retrospectively analyzed the proportion of septic shock cases receiving an early (day of admission) central venous catheter and the odds of hospital mortality associated with receiving early central venous catheter from years 1998 to 2001 compared with 2002 to 2009. Setting:Non-federal acute care hospitalizations from the Nationwide Inpatient Sample, 1998–2009. Patients:A total of 203,481 (population estimate: 999,545) patients admitted through an emergency department with principal diagnosis of septicemia and secondary diagnosis of shock. Interventions:None. Measurements and Main Results:From 1998 to 2009, population-adjusted rates of septic shock increased from 12.6 cases per 100,000 U.S. adults to 78 cases per 100,000. During this time, age-adjusted hospital mortality associated with septic shock declined from 40.4% to 31.4%. Early central venous catheter insertion increased from 5.7% (95% confidence interval 5.1% to 6.3%) to 19.2% (95% confidence interval 18.7% to 19.5%) cases with septic shock, with an increased rate of early central venous catheter placement identified after 2007. The rate of decline in age-adjusted hospital mortality was significantly greater for patients who received an early central venous catheter (–4.2% per year, 95% confidence interval –3.2, –4.2%) as compared with no central venous catheter (–2.9% per year, 95% confidence interval –2.3, –3.5%; p = 0.016). Hospital mortality associated with early central venous catheter insertion significantly decreased from a multivariable-adjusted odds ratio of 1.29 (95% confidence interval 1.14–1.45) prior to 2001 to an adjusted odds ratio of 0.87 (95% confidence interval 0.84–0.90) after 2001. Conclusions:Placement of a central venous catheter early in septic shock has increased three-fold since 1998. The mortality associated with early central venous catheter insertion decreased after publication of evidence-based instructions for central venous catheter use.