Robert Sherwin

Early Goal-Directed Therapy in Severe Sepsis and Septic Shock Revisited: Concepts, Controversies, and Contemporary Findings

Studies of acute myocardial infarction, trauma, and stroke have been translated into improved outcomes by earlier diagnosis and application of therapy at the most proximal stage of hospital presentation. Most therapies for these diseases are instituted prior to admission to an ICU; this approach to the sepsis patient has been lacking. In response, a trial comparing early goal-directed therapy (EGDT) vs standard care was performed using specific criteria for the early identification of high-risk sepsis patients, verified definitions, and a consensus-derived protocol to reverse the hemodynamic perturbations of hypovolemia, vasoregulation, myocardial suppression, and increased metabolic demands. Five years after the EGDT publication, there has been much discussion generated with regard to the concepts of EGDT, as well as debate fueled regarding diagnostic and therapeutic interventions. However, during this time period further investigations by the primary investigators and others have brought additional contemporary findings. EGDT modulates some of the components of inflammation, as reflected by improved organ function. The end points used in the EGDT protocol, the outcome results, and the cost-effectiveness have subsequently been externally validated, revealing similar or even better findings than those from the original trial. Although EGDT is faced with challenges, a coordinated approach to sepsis management is necessary to duplicate the progress in outcomes seen in patients with conditions such as acute myocardial infarction, stroke, and trauma.

Postgraduate Education CornerEarly Goal-Directed Therapy in Severe Sepsis and Septic Shock Revisited: Concepts, Controversies, and Contemporary Findings

Studies of acute myocardial infarction, trauma, and stroke have been translated into improved outcomes by earlier diagnosis and application of therapy at the most proximal stage of hospital presentation. Most therapies for these diseases are instituted prior to admission to an ICU; this approach to the sepsis patient has been lacking. In response, a trial comparing early goal-directed therapy (EGDT) vs standard care was performed using specific criteria for the early identification of high-risk sepsis patients, verified definitions, and a consensus-derived protocol to reverse the hemodynamic perturbations of hypovolemia, vasoregulation, myocardial suppression, and increased metabolic demands. Five years after the EGDT publication, there has been much discussion generated with regard to the concepts of EGDT, as well as debate fueled regarding diagnostic and therapeutic interventions. However, during this time period further investigations by the primary investigators and others have brought additional contemporary findings. EGDT modulates some of the components of inflammation, as reflected by improved organ function. The end points used in the EGDT protocol, the outcome results, and the cost-effectiveness have subsequently been externally validated, revealing similar or even better findings than those from the original trial. Although EGDT is faced with challenges, a coordinated approach to sepsis management is necessary to duplicate the progress in outcomes seen in patients with conditions such as acute myocardial infarction, stroke, and trauma.

Biomarkers of endothelial cell activation in early sepsis.

Purpose The objective of this study was to investigate the association of endothelial-related markers with organ dysfunction and in-hospital mortality to validate our earlier findings in a multicenter study. We hypothesize that (i) endothelial biomarkers will be associated with organ dysfunction and mortality in sepsis and that (ii) soluble fms-like tyrosine kinase 1 (sFlt-1) holds promise as a novel prognostic marker in sepsis. Methods This was a prospective, multicenter, observational study of a convenience sample of emergency department (ED) patients with a suspected infection presenting to one of four urban, academic medical center EDs between January 2009 and January 2010. We collected plasma while the patients were in the ED and subsequently assayed endothelial-related biomarkers, namely, sFlt-1, soluble E-selectin, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and plasminogen activator inhibitor 1 (PAI-1). Outcomes were organ dysfunction and in-hospital mortality. Results We enrolled a total of 166 patients: 63 with sepsis (38%), 61 with severe sepsis (37%), and 42 with septic shock (25%). All endothelial biomarkers were significantly associated with sepsis severity, P < 0.002. We found a significant intercorrelation between all biomarkers, strongest between sFlt-1 and PAI-1 (r = 0.61, P < 0.001) and PAI-1 and soluble E-selectin and soluble intercellular adhesion molecule 1 (r = 0.49, P < 0.001). Among the endothelial biomarkers, sFlt-1 had the strongest association with Sequential Organ Failure Assessment score (r = 0.58, P < 0.001). Soluble fms-like tyrosine kinase 1 and PAI-1 had the highest area under the operating receiver characteristic curve for mortality of 0.87. Conclusions This multicenter validation study confirms that markers of endothelial activation are associated with sepsis severity, organ dysfunction, and mortality in sepsis. This supports the hypothesis that the endothelium plays a central role in the pathophysiology of sepsis and may serve as a more accurate prediction tool and a target for therapies aimed at ameliorating endothelial cell dysfunction. In addition, sFLT-1 holds promise as a novel sepsis severity biomarker.

Distribution of 13-Valent Pneumococcal Conjugate Vaccine Streptococcus pneumoniae Serotypes in US Adults Aged ≥50 Years With Community-Acquired Pneumonia

BACKGROUND Streptococcus pneumoniae causes a substantial proportion of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) in the United States. Limited data are available regarding the pneumococcal serotypes causing CAP and HCAP. METHODS Adults aged ≥ 50 years presenting to participating US hospitals with radiographically confirmed pneumonia between February 2010 and September 2011 were screened for inclusion. S. pneumoniae was identified using microbiological cultures, BinaxNOW® S. pneumoniae assay, or urine antigen detection (UAD) assay capable of detecting 13-valent pneumococcal conjugate vaccine (PCV13)-associated serotypes. RESULTS Among 710 subjects enrolled, the median age was 65.4 years; 54.2% of subjects were male, 22.4% of radiographically confirmed pneumonia cases were considered HCAP, and 96.6% of subjects were hospitalized. S. pneumoniae was detected in 98 subjects (13.8%) by any test, and PCV13-associated serotype(s) were identified by UAD in 78 (11.0%). Serotype 19A was most prevalent, followed by 7F/A, 3, and 5. Serotypes associated with 7-valent pneumococcal conjugate vaccine (PCV7) accounted for 25% of UAD-positive isolates. CONCLUSIONS Pneumococcal serotypes causing noninvasive pneumonia in adults may differ significantly from those causing invasive disease, with PCV7-associated serotypes overrepresented. Serotype 5, rarely seen in contemporary surveillance of invasive disease in the United States, substantially contributed to the observed cases of S. pneumoniae-positive CAP or HCAP.

Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin Monitoring Sepsis (moses) Study

Objectives: To prospectively validate that the inability to decrease procalcitonin levels by more than 80% between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis patient population recruited across the United States. Design: Blinded, prospective multicenter observational clinical trial following an Food and Drug Administration-approved protocol. Setting: Thirteen U.S.-based emergency departments and ICUs. Patients: Consecutive patients meeting criteria for severe sepsis or septic shock who were admitted to the ICU from the emergency department, other wards, or directly from out of hospital were included. Interventions: Procalcitonin was measured daily over the first 5 days. Measurements and Main Results: The primary analysis of interest was the relationship between a procalcitonin decrease of more than 80% from baseline to day 4 and 28-day mortality using Cox proportional hazards regression. Among 858 enrolled patients, 646 patients were alive and in the hospital on day 4 and included in the main intention-to-diagnose analysis. The 28-day all-cause mortality was two-fold higher when procalcitonin did not show a decrease of more than 80% from baseline to day 4 (20% vs 10%; p = 0.001). This was confirmed as an independent predictor in Cox regression analysis (hazard ratio, 1.97 [95% CI, 1.18–3.30; p < 0.009]) after adjusting for demographics, Acute Physiology and Chronic Health Evaluation II, ICU residence on day 4, sepsis syndrome severity, antibiotic administration time, and other relevant confounders. Conclusions: Results of this large, prospective multicenter U.S. study indicate that inability to decrease procalcitonin by more than 80% is a significant independent predictor of mortality and may aid in sepsis care.

Cardiac Complications in Acute Ischemic Stroke

Introduction To characterize cardiac complications in acute ischemic stroke (AIS) patients admitted from an urban emergency department (ED). Methods Retrospective cross-sectional study evaluating AIS patients admitted from the ED within 24 hours of symptom onset who also had an echocardiogram performed within 72 hours of admission. Results Two hundred AIS patients were identified with an overall in-hospital mortality rate of 8% (n = 16). In our cohort, 57 (28.5%) of 200 had an ejection fraction less than 50%, 35 (20.4%) of 171 had ischemic changes on electrocardiogram (ECG), 18 (10.5%) of 171 presented in active atrial fibrillation, 21 (13.0%) of 161 had serum troponin elevation, and 2 (1.1%) of 184 survivors had potentially lethal arrhythmias on telemetry monitoring. Subgroup analysis revealed higher in-hospital mortality rates among those with systolic dysfunction (15.8% versus 4.9%; P = 0.0180), troponin elevation (38.1% versus 3.4%; P < 0.0001), atrial fibrillation on ECG (33.3% versus 3.8%; P = 0.0003), and ischemic changes on ECG (17.1% versus 6.1%; P = 0.0398) compared with those without. Conclusion A proportion of AIS patients may have cardiac complications. Systolic dysfunction, troponin elevation, atrial fibrillation, or ischemic changes on ECG may be associated with higher in-hospital mortality rates. These findings support the adjunctive role of cardiac-monitoring strategies in the acute presentation of AIS.

ED intensivists and ED intensive care units

a Division of Emergency Critical Care, Mount Sinai School of Medicine, New York, NY, USA b Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI, USA c Departments of Critical Care Medicine & Emergency Medicine, University of Pittsburgh, Pittsburgh, PA, USA d Department of Surgery/ Department of Emergency Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USA e Department of Emergency Medicine & Department of Surgery, Division of Trauma/Critical Care, Virginia Commonwealth University, Richmond, VA, USA f Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA, USA

Noninvasive Hemodynamic Monitoring in Emergency Patients with Suspected Heart Failure, Sepsis and Stroke: The Premium Registry

Introduction Noninvasive hemodynamic (HD) assessments in the emergency department (ED) might assist in the diagnosis, therapeutic plan development and risk stratification of acutely ill patients. This multinational observational study was designed to initiate noninvasive HD measurements prior to any ED patient therapeutic interventions and broadly evaluate them for potential diagnostic, therapeutic and predictive value. Methods We enrolled patients with suspected acute heart failure (AHF), sepsis or stroke. Continuous noninvasive HD monitoring was begun using the Nexfin finger cuff device (Edwards LifeSciences, BMEYE, Amsterdam, Netherlands). Beat-to-beat HD measurements were averaged for the initial 15 minutes, prior to therapeutic intervention. We performed suspected disease group comparisons and evaluated HD predictors of 30-day mortality. Results Of 510 patients enrolled: 185 (36%) AHF, 194 (38%) sepsis and 131 (26%) stroke. HD variables were significantly different (p<0.05) amongst the groups. Cardiac output and index and stroke volume index (SVI) were highest in sepsis (6.5, 3.5, 36), followed by stroke (5.5, 2.7, 35.8), and lowest in AHF (5.4, 2.7, 33.6). The in-group HD standard deviations and ranges measurements were large, indicating heterogeneous underlying HD profiles. Presenting SVI predicted 30-day mortality for all groups. Conclusion Presenting ED noninvasive HD data has not been previously reported in any large patient population. Our data suggest a potential role for early noninvasive HD assessments aiding in diagnosing of patients, individualizing therapy based on each person’s unique HD values and predicting 30-day mortality. Further studies and analyses are needed to determine how HD assessments should be best used in the ED.

Hyperbaric oxygen therapy for systemic gas embolism after hydrogen peroxide ingestion.

BACKGROUND Hydrogen peroxide is a commonly available product and its ingestion has been demonstrated to produce in vivo gas bubbles, which can embolize to devastating effect. OBJECTIVE We report two cases of hydrogen peroxide ingestion with resultant gas embolization, one to the portal system and one cerebral embolus, which were successfully treated with hyperbaric oxygen therapy (HBO), and review the literature. CASE REPORT Two individuals presented to our center after unintentional ingestion of concentrated hydrogen peroxide solutions. Symptoms were consistent with portal gas emboli (Patient A) and cerebral gas emboli (Patient B), which were demonstrated on imaging. They were successfully treated with HBO and recovered without event. CONCLUSIONS As demonstrated by both our experience as well as the current literature, HBO has been used to successfully treat gas emboli associated with hydrogen peroxide ingestion. We recommend consideration of HBO in any cases of significant hydrogen peroxide ingestion with a clinical picture compatible with gas emboli.

Modifiable factors associated with severe asthma exacerbations in urban patients

BACKGROUND Rates of asthma morbidity, mortality, and resource use are highest among African American individuals residing in inner-city locations, yet factors associated with adverse outcomes are not well established. OBJECTIVE To identify modifiable factors associated with asthma exacerbations. METHODS A total of 104 adult patients who presented to an inner-city hospital or emergency department (ED) with an asthma exacerbation from October 1, 2009, through June 31, 2010, completed surveys of clinical status, acute events, sociodemographic characteristics, current asthma knowledge, self-efficacy, attitudes toward asthma self-management, and perceived barriers to asthma care questionnaires. Associations with asthma hospitalizations and ED visits were assessed. RESULTS The mean age of the patients was 42 years, 91% were African American, 33% were insured, 57% were taking a controller medication, and 63% had an income level below the federal poverty line. On bivariate analysis, males, years of asthma, history of smoking, self-classification of asthma severity, history of admission to intensive care unit or intubation, use of peak flow meter or asthma action plan, controller medication use, and history of oral corticosteroid bursts were positively associated, whereas self-efficacy was negatively associated with number of ED visits or hospitalizations. No association was found for asthma knowledge, perceived barriers to care, or attitudes toward asthma management. On multivariate analysis, low self-efficacy remained associated with both asthma hospitalizations and ED visits. CONCLUSION Short-term use of health services for asthma is negatively associated with asthma self-efficacy. Self-management programs that enhance self-efficacy, rather than those that focus on knowledge or attitudes, may be effective in reducing adverse asthma outcomes for inner-city, predominantly African American populations.