Donald M. Yealy

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.).

Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial

BACKGROUND Although practice guidelines recommend outpatient care for selected, haemodynamically stable patients with pulmonary embolism, most treatment is presently inpatient based. We aimed to assess non-inferiority of outpatient care compared with inpatient care. METHODS We undertook an open-label, randomised non-inferiority trial at 19 emergency departments in Switzerland, France, Belgium, and the USA. We randomly assigned patients with acute, symptomatic pulmonary embolism and a low risk of death (pulmonary embolism severity index risk classes I or II) with a computer-generated randomisation sequence (blocks of 2-4) in a 1:1 ratio to initial outpatient (ie, discharged from hospital ≤24 h after randomisation) or inpatient treatment with subcutaneous enoxaparin (≥5 days) followed by oral anticoagulation (≥90 days). The primary outcome was symptomatic, recurrent venous thromboembolism within 90 days; safety outcomes included major bleeding within 14 or 90 days and mortality within 90 days. We used a non-inferiority margin of 4% for a difference between inpatient and outpatient groups. We included all enrolled patients in the primary analysis, excluding those lost to follow-up. This trial is registered with ClinicalTrials.gov, number NCT00425542. FINDINGS Between February, 2007, and June, 2010, we enrolled 344 eligible patients. In the primary analysis, one (0·6%) of 171 outpatients developed recurrent venous thromboembolism within 90 days compared with none of 168 inpatients (95% upper confidence limit [UCL] 2·7%; p=0·011). Only one (0·6%) patient in each treatment group died within 90 days (95% UCL 2·1%; p=0·005), and two (1·2%) of 171 outpatients and no inpatients had major bleeding within 14 days (95% UCL 3·6%; p=0·031). By 90 days, three (1·8%) outpatients but no inpatients had developed major bleeding (95% UCL 4·5%; p=0·086). Mean length of stay was 0·5 days (SD 1·0) for outpatients and 3·9 days (SD 3·1) for inpatients. INTERPRETATION In selected low-risk patients with pulmonary embolism, outpatient care can safely and effectively be used in place of inpatient care. FUNDING Swiss National Science Foundation, Programme Hospitalier de Recherche Clinique, and the US National Heart, Lung, and Blood Institute. Sanofi-Aventis provided free drug supply in the participating European centres.

National estimates of severe sepsis in United States emergency departments.

Objective:The emergency department (ED) often serves as the first site for the recognition and treatment of patients with suspected severe sepsis. However, few evaluations of the national epidemiology and distribution of severe sepsis in the ED exist. We sought to determine national estimates of the number, timing, ED length of stay, and case distribution of patients presenting to the ED with suspected severe sepsis. Design:Analysis of 2001–2004 ED data from the National Hospital Ambulatory Medical Care Survey. Setting:National multistage probability sample of United States ED data. Patients:Adult (age, ≥18 yrs) patients with suspected severe sepsis, defined as the concurrent presence of an infec-tion (ED International Classification of Diseases, 9th Revision; ICD-9) diagnosis of infection, or a triage temperature <96.8°F or ≥100.4°F) and organ dysfunction (ED ICD-9) diagnosis of organ dysfunction, intubation, or a triage systolic blood pressure ≤90 mm Hg). Interventions:None. Measurements:Estimated number of ED patients presenting with suspected severe sepsis, and their times of arrival, ED lengths of stay, and clinical characteristics. Main Results:Of 331.5 million adult ED visits, approximately 2.3 million (571,000 annually, 0.69%; 95% confidence interval [CI], 0.61–0.77%) were for suspected severe sepsis. Mean ED length of stay for suspected severe sepsis was 4.7 hrs (95% CI, 4.3–5.1 hrs), with 20.4% spending >6 hrs in the ED. Of suspected severe sepsis patients, 20.6% presented to a low-volume ED (≤20,000 annual visits), 15.6% presented to ED in non–Metropolitan Statistical Areas, and 53.5% presented to EDs without medical school affiliations. More than half arrived by ambulance. Conclusions:Suspected severe sepsis patients account for more than 500,000 ED visits annually, with individual patients spending an average of almost 5 hrs in the ED. These national data offer key systemwide information for designing and implementing strategies for severe sepsis treatment.

Use of Automated External Defibrillators by Police Officers for Treatment of Out-of-Hospital Cardiac Arrest

OBJECTIVE To determine the feasibility of police officers providing defibrillation with automated external defibrillators (AEDs) and to assess the effectiveness of this strategy in reducing time to defibrillation of victims of out-of-hospital sudden cardiac arrest. METHODS This was a prospective, interventional cohort study with historical controls conducted in 7 suburban communities in which police usually arrived at the scene of medical emergencies before EMS personnel. All adult patients who suffered cardiac arrest before EMS arrival and on whom EMS personnel attempted resuscitation were enrolled. Police officers who were trained to use and equipped with AEDs during the intervention phase were dispatched simultaneously with EMS to medical emergencies. Police were instructed to use the AED immediately on determination of pulselessness. Outcome measures were the difference between control and intervention phases in interval from the time the call was received at dispatch to the time of first defibrillation and in rate of survival to hospital discharge for patients initially in ventricular fibrillation. RESULTS EMS personnel attempted 183 resuscitations in the control phase and 283 during the intervention; of these, 80 (44%) and 127 (45%), respectively, involved patients with initial ventricular fibrillation rhythms. Mean time to defibrillation decreased from 11.8+/-4.7 minutes in the control phase to 8.7+/-3.7 minutes in the intervention phase (P<.0001). Survival to hospital discharge of patients in ventricular fibrillation did not differ between phases (6% control versus 14% intervention, P=.1). When police arrived before EMS personnel, shock administered by police compared with shock administered by EMS was associated with improved survival (26% [12/46] versus 3% [1/29], P=.01). Logistic regression analysis revealed AED use was an independent predictor of survival to hospital discharge. CONCLUSION In 7 suburban communities, police use of AEDs decreased time to defibrillation and was an independent predictor of survival to hospital discharge.

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

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.

Defining the Learning Curve for Paramedic Student Endotracheal Intubation

Background. Proficiency in endotracheal intubation (ETI) is assumed to improve primarily with accumulated experience on live patients. While the National Standard Paramedic Curriculum recommends that paramedic students (PSs) perform at least five live ETIs, these training opportunities are limited. Objective. To evaluate the effects of cumulative live ETI experience, elapsed duration of training, andclinical setting on PS ETI proficiency. Methods. The authors used longitudinal, multicenter data from 60 paramedic training programs over a two-year period. The PSs reported outcomes (success/failure) for all live ETIs attempted in the operating room (OR), the emergency department (ED), the intensive care unit (ICU), andother hospital or prehospital settings. Fixed-effects logistic regression was used to model up to 30 consecutive ETI efforts by each PS, accounting for per-PS clustering. For each patient, the authors evaluated the association between ETI success andthe PSs cumulative number of ETIs, adjusted for clinical setting, elapsed number of days from the first ETI encounter, andthe interaction (cumulative ETIs × elapsed days). Predicted probability plots were constructed depicting the “learning curve” overall andfor each clinical setting. Results. Between one and74 ETIs (median 7; IQR 4–12) were performed by each of 802 PSs. Of 7,635 ETIs, 6,464 (87.4%) were successful. Stratified by clinical setting, 6,311 (82.7%) ETIs were performed in the OR, 271 (3.6%) in the ED, 64 (0.8%) in the ICU, 86 (1.1%) in other in-hospital settings, and903 (11.8%) in the prehospital setting. For the 7,398 ETIs included in the multivariate analysis, cumulative number of ETI was associated with increased adjusted odds of ETI success (odds ratio 1.067 per ETI; 95% CI: 1.044–1.091). ETI learning curves were steepest for the ICU andprehospital settings but lower than for other clinical settings. Conclusions. Paramedic student ETI success improves with accumulated live experience but appears to vary across different clinical settings. Strategies for PS airway education must consider the volume of live ETIs as well as the clinical settings used for ETI training. Key words: intubation; intratracheal; emergency medical services; learning; allied health personnel.

Verification of endotracheal tube placement with colorimetric end-tidal CO2 detection

STUDY OBJECTIVE To determine the ability of a disposable colorimetric CO2 detector to accurately confirm or refute endotracheal tube placement. DESIGN Two hundred fifty prospective emergency intubations. SETTING Emergency intubations performed in the emergency department, helicopter, and prehospital ground environment. TYPE OF PARTICIPANTS Intubations were performed by emergency medicine residents, paramedics, and flight nurses. INTERVENTIONS The FEF CO2 detector was applied after 250 emergency intubations. Notation of color change indicating intratracheal placement was recorded in each case. Confirmation of refutation of the detectors results was determined subsequently through traditional methods. RESULTS The sensitivity for confirmation of endotracheal intubation in the 137 patients with a palpable pulse was 100%. However, only 76 of 103 patients (sensitivity, 72%) in cardiac arrest had endotracheal intubation confirmed by color change. The device was uniformly specific for tracheal intubation in 73 arrested patients in whom a color change was noted (100%). There was one instance (of a total of seven misintubations) in which a positive color change was noted, but the tube was not intratracheal (specificity, 86%). Overall sensitivity for tracheal intubation was 88% (95% confidence limits; range, 0.83 to 0.92), and specificity for tracheal intubation was 92% (95% confidence limits; range, 0.62 to 0.99). CONCLUSION The FEF colorimetric detector reliably detects intratracheal placement in the nonarrested patient. Its use in prolonged cardiac arrest merits further study.

Out-of-hospital airway management in the United States ,

OBJECTIVE Prior studies describe airway management by single EMS agencies, regions or states. We sought to characterize out-of-hospital airway management interventions, outcomes and complications across the United States. METHODS Using the 2008 National Emergency Medical Services Information System (NEMSIS) Public-Release Data Set containing data from 16 states, we identified patients receiving advanced airway management, including endotracheal intubation (ETI), alternate airways (Combitube, Laryngeal Mask Airway (LMA), King LT, Esophageal-Obturator Airway (EOA)), and cricothyroidotomy (needle and open). We examined airway management success and complications in the full cohort and in key subsets (cardiac arrest, non-arrest medical, non-arrest injury, children <10 and 10-19 years, rapid-sequence intubation (RSI), population setting and US census region). We analyzed the data using descriptive statistics. RESULTS Among 4,383,768 EMS activations, there were 10,356 ETI, 2246 alternate airways, and 88 cricothyroidotomies. ETI success rates were: overall 6482/8418 (77.0%; 95% CI: 76.1-77.9%), cardiac arrest 3494/4482 (78.0%), non-arrest medical 616/846 (72.8%), non-arrest injury 417/505 (82.6%), children <10 years 295/397 (74.3%), children 10-19 years 228/289 (78.9%), adult 5829/7552 (77.2%), and rapid-sequence intubation 289/355 (81.4%). ETI success was success was lowest in the South US census region. Alternate airway success was 1564/1794 (87.2%). Major complications included: bleeding 84 (7.0 per 1000 interventions), vomiting 80 (6.7 per 1000) and esophageal intubation 12 (1.0 per 1000). CONCLUSIONS In this study characterizing out-of-hospital airway management across the United States, we observed low out-of-hospital ETI success rates. These data may guide national efforts to improve the quality of out-of-hospital airway management.

Frequent Users of Emergency Department Services: Gaps in Knowledge and a Proposed Research Agenda

Frequent use of emergency department (ED) services is often perceived to be a potentially preventable misuse of resources. The underlying assumption is that similar and more appropriate care can be delivered outside of EDs at a lower cost. To reduce costs and incentivize more appropriate use of services, there have been efforts to design interventions to transition health care utilization of frequent users from EDs to other settings such as outpatient clinics. Many of these efforts have succeeded in smaller trials, but wider use remains elusive for varying reasons. There are also some fundamental problems with the assumption that all or even the majority of frequent ED use is misuse and invoking reasons for that excessive use. These tenuous assumptions become evident when frequent users as a group are compared to less frequent users. Specifically, frequent users tend to have high levels of frequent ED use, have a higher severity of illness, be older, have fewer personal resources, be chronically ill, present for pain-related complaints, and have government insurance (Medicare or Medicaid). Because of the unique characteristics of the population of frequent users, we propose a research agenda that aims to increase the understanding of frequent ED use, by: 1) creating an accepted categorization system for frequent users, 2) predicting which patients are at risk for becoming or remaining frequent users, 3) implementing both ED- and non-ED-based interventions, and 4) conducting qualitative studies of frequent ED users to explore reasons and identify factors that are subject to intervention and explore specific differences among populations by condition, such as mental illness and heart failure.

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.