Steven Q. Simpson

Cardiopulmonary manifestations of hantavirus pulmonary syndrome.

OBJECTIVE To describe the clinical characteristics of a group of patients infected with the newly recognized hantavirus in the Southwestern United States. DESIGN Case series. SETTING Tertiary referral center. PATIENTS All patients with confirmed hantavirus infection admitted to the University of New Mexico Hospital between May 1, 1993 and January 1, 1994. INTERVENTIONS Records of patients with hantavirus infection were reviewed to collect all pertinent clinical data. MEASUREMENTS AND MAIN RESULTS Pulmonary disease in these patients was characterized by hypoxemia covering a wide range of severity. The cause of hypoxemia was an increased permeability (noncardiac) pulmonary edema which could be differentiated from hydrostatic (cardiac) pulmonary edema by its association with low pulmonary artery occlusion pressures and increased protein content of edema fluid. Hemodynamic measurements in severe cases showed a shock state characterized by a low cardiac index (range 1.6 to 3.0 L/min/min2), a low stroke volume index (range 10.5 to 29 mL/m2), and high systemic vascular resistance index (range 1,653 to 2,997 dyne.sec/cm5.m2). Progression to death was associated with worsening cardiac dysfunction unresponsive to treatment and causing oxygen debt and lactic acidosis. CONCLUSIONS The two major life-threatening pathophysiologic changes in Hantavirus Pulmonary Syndrome are increased permeability pulmonary edema, and an atypical form of septic shock caused by myocardial depression and hypovolemia.

Successful treatment of adults with severe Hantavirus pulmonary syndrome with extracorporeal membrane oxygenation.

OBJECTIVE To describe our experience with the use of extracorporeal membrane oxygenation (ECMO) as a rescue therapy in adult patients with severe cardiopulmonary failure from Hantavirus pulmonary syndrome. DESIGN Case series. SETTING Tertiary referral center. PATIENTS Patients with confirmed Hantavirus infection, who developed severe cardiopulmonary failure in which conventional therapy was assessed as being unsuccessful. INTERVENTIONS Records of previous patients treated for Hantavirus pulmonary syndrome were reviewed and findings consistent with 100% mortality were found. MEASUREMENTS AND MAIN RESULTS Findings associated with a 100% mortality rate were a) cardiac index of <2.5 L/min/m2; b) serum lactate concentration of >4.0 mmol/L (normal range 0.0 to 2.2); c) pulseless electrical activity or ventricular fibrillation or ventricular tachycardia; and d) refractory shock despite fluid resuscitation, and vasoactive medications. From 1994 to 1996, seven patients were admitted with confirmed Hantavirus pulmonary syndrome and severe cardiopulmonary failure. Three of the seven patients had at least two of the four criteria for a 100% mortality rate listed above, and appeared to be failing optimal conventional therapy. These three patients received support with venoarterial ECMO. The first patient was placed on ECMO during cardiac arrest and died. The next two patients who received ECMO for Hantavirus pulmonary syndrome survived after relatively short, uncomplicated ECMO runs, and were discharged without complications. CONCLUSIONS ECMO successfully provided cardiopulmonary support in two patients with severe Hantavirus pulmonary syndrome who survived with a good outcome. Our experience suggests that ECMO is a beneficial therapy for patients critically ill with Hantavirus pulmonary syndrome.

An Official Multi-Society Statement: The Role of Clinical Research Results in the Practice of Critical Care Medicine

BACKGROUND While the results of clinical research are clearly valuable in the care of critically ill patients, the limitations of such information and the role of other forms of medical knowledge for clinical decision making have not been carefully examined. METHODS The leadership of three large professional societies representing critical care practitioners convened a diverse group representing a wide variety of views regarding the role of clinical research results in clinical practice to develop a document to serve as a basis for agreement and a framework for ongoing discussion. RESULTS Consensus was reached on several issues. While the results of rigorous clinical research are important in arriving at the best course of action for an individual critically ill patient, other forms of medical knowledge, including clinical experience and pathophysiologic reasoning, remain essential. No single source of knowledge is sufficient to guide clinical decisions, nor does one kind of knowledge always take precedence over others. Clinicians will find clinical research compelling for a variety of reasons that go beyond study design. While clinical practice guidelines and protocols based upon clinical research may improve care and decrease variability in practice, clinicians must be able to understand and articulate the rationale as to why a particular protocol or guideline is used or why an alternative approach is taken. Making this clinical reasoning explicit is necessary to understand practice variability. CONCLUSIONS Understanding the strengths and weaknesses of different kinds of medical knowledge for clinical decision making and factors beyond study design that make clinical research compelling to clinicians can provide a framework for understanding the role of clinical research in practice.

Reduced alveolar macrophage production of tumor necrosis factor during sepsis in mice and men

Background and MethodsTumor necrosis factor (TNF) has been implicated as a major humoral mediator of sepsis and endotoxin shock. TNF is secreted by cells of the reticuloendothelial system, including alveolar macrophages. Alveolar macrophage TNF production has been postulated to play a pathogenetic role in the development of adult respiratory distress syndrome (ARDS) in sepsis. To evaluate alveolar macrophage production of TNF during sepsis and endotoxin shock, we studied the effects of sepsis and/or in vivo lipopolysac-charide on the in vitro production of TNF by pulmonary alveolar macrophages. Human pulmonary alveolar macrophages were obtained by bronchoalveolar lavage from six septic and five nonseptic patients, cultured in the presence or absence of lipopolysaccharide (1 ng/mL), and assayed for TNF activity in a bioassay using fibroblast lysis. A murine model of sepsis was also utilized to study pulmonary alveolar macrophage TNF production under more controlled conditions. Normal mice were given ip injections of either lipopolysaccharide or saline. After 2 hrs, pulmonary alveolar macrophages were obtained and cultured in saline or various concentrations of lipopolysaccharide (0.001 to 10 μg/mL). ResultsThere was no difference in baseline TNF activity, expressed as per cent lysis at 1:10 dilution, between pulmonary alveolar macrophages from control and septic patients (35.7 ± 5.5% vs. 24.4 ± 9.3%, respectively) (p > .05). However, when stimulated with lipopolysaccharide in vitro, the pulmonary alveolar macrophages from nonseptic patients produced significantly (p < .01) more TNF (82.8 ± 3.6%) than did pulmonary alveolar macrophages from patients with the septic syndrome (35.2 ± 3.8%). Similar findings were obtained using the murine sepsis model. The baseline TNF activity in pulmonary alveolar macrophages from control mice was 22.9 ± 7.0% (mean ± SEM) and from lipopolysaccharide-injected mice was 26.8 ± 3.3% (p > .05). Stimulation with 1 ng/mL lipopolysaccharide in vitro produced an increase in TNF activity in both groups, but the increase was greater in the control mice (68.1 ± 5.7%) than in the lipopolysaccharide-injected mice (47.5 ± 5.3%) (p < .01). When the murine pulmonary alveolar macrophages were stimulated with higher concentrations of lipopolysaccharide (0.1 to 10 ug/mL), pulmonary alveolar macrophages from lipopolysaccharide-injected mice produced <25.5% of the TNF produced by pulmonary alveolar macrophages from control mice. ConclusionsThese studies indicate that sepsis and endotoxin injection result in a rapid decrease in the ability of pulmonary alveolar macrophages from both humans and mice to produce and secrete TNF in response to lipopolysaccharide. We speculate that a downregulation of TNF production or of macrophage responsiveness to lipopolysaccharide has occurred. These results suggest that sustained TNF production by macrophages is not required for lung injury in sepsis.

Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome, also known as hantavirus cardiopulmonary syndrome, is a recently described infectious syndrome found throughout the Americas. Although infection is sporadic and uncommon compared with other atypical pneumonia syndromes, its high mortality rate warrants the maintenance of a high index of suspicion in rural settings. Because no specific therapies are available for the disease, prevention and early recognition play an important role in reducing mortality from the disease. This article reviews the nature of the viruses that cause hantavirus pulmonary syndrome, the epidemiology and ecology of disease transmission, and disease recognition, treatment, and prevention.

Electromagnetic navigational bronchoscopy in the diagnosis of lung lesions.

Background:The diagnosis of pulmonary lesions that are not bronchoscopically visible is a challenging process. Electromagnetic navigation bronchoscopy (ENB) is a new technology designed to diagnose peripheral pulmonary lesions. We sought to determine whether diagnostic yield from ENB was affected by bronchus sign, lesion location, or size. Methods:Data were obtained retrospectively from all patients undergoing ENB at our institution since 2008. ENB was performed by 3 separate proceduralists at our institution from November 2008 until July 2011 using the superDimension/InReach system. Patient selection and modalities of specimen collection were at the discretion of the proceduralist. All procedures were performed using general anesthesia and fluoroscopy. Lesion size, location, diagnosis from ENB, and eventual diagnosis were recorded. Results:Fifty-five individuals underwent ENB between 2008 and 2011. The average lesion size was 3.0 cm and the majority of lesions were located in the upper lobes (34/55 lesions). Of the 55 patients, in 41, a diagnosis was established from ENB, a diagnostic yield of 74.5%. Thirty-six patients were eventually diagnosed with a malignancy, of whom 25 were diagnosed by ENB, yielding a sensitivity for malignancy of 69.4%. The negative predictive value for malignancy with an ENB procedure was 54.2%. There were 2 cases of postprocedure respiratory failure, but there were no cases of pneumothorax. Bronchus sign, lesion size, and location did not affect the diagnostic yield. Conclusions:ENB shows an acceptable diagnostic yield with an excellent safety profile in the diagnosis of pulmonary lesions. The use of fluoroscopy and general anesthesia may improve the diagnostic yield.

Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients.

Objectives: To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock. Design: Retrospective cohort. Setting: Six hundred fifty-six bed urban academic medical center. Patients: Emergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded. Interventions: Not available. Measurements and Main Results: We identified 3,929 severe sepsis patients, with overall mortality 12.8%. Nine hundred eighty-four patients (25.0%) progressed to septic shock. The median time to antimicrobial was 3.77 hours (interquartile range = 1.96–6.42) in those who progressed versus 2.76 hours (interquartile range = 1.60–4.82) in those who did not (p < 0.001). Multivariate logistic regression demonstrated that male sex (odds ratio = 1.18; 95% CI, 1.01–1.36), Charlson Comorbidity Index (odds ratio = 1.18; 95% CI, 1.11–1.27), number of infections (odds ratio = 1.05; 95% CI, 1.02–1.08), and time to first antimicrobial (odds ratio = 1.08; 95% CI, 1.06–1.10) were associated with progression. Each hour until initial antimicrobial administration was associated with a 8.0% increase in progression to septic shock. Additionally, time to broad-spectrum antimicrobial was associated with progression (odds ratio = 1.06; 95% CI, 1.05–1.08). Time to initial antimicrobial was also associated with in-hospital mortality (odds ratio = 1.05; 95% CI, 1.03–1.07). Conclusions: This study emphasizes the importance of early, broad-spectrum antimicrobial administration in severe sepsis patients admitted through the emergency department, as longer time to initial antimicrobial administration is associated with increased progression of severe sepsis to septic shock and increased mortality.

Training internists to meet critical care needs in the United States: A consensus statement from the critical care societies collaborative (CCSC)

Objectives:Multiple training pathways are recognized by the Accreditation Council for Graduate Medical Education (ACGME) for internal medicine (IM) physicians to certify in critical care medicine (CCM) via the American Board of Internal Medicine. While each involves 1 year of clinical fellowship training in CCM, substantive differences in training requirements exist among the various pathways. The Critical Care Societies Collaborative convened a task force to review these CCM pathways and to provide recommendations for unified and coordinated training requirements for IM-based physicians. Participants:A group of CCM professionals certified in pulmonary-CCM and/or IM-CCM from ACGME-accredited training programs who have expertise in education, administration, research, and clinical practice. Data Sources and Synthesis:Relevant published literature was accessed through a MEDLINE search and references provided by all task force members. Material published by the ACGME, American Board of Internal Medicine, and other specialty organizations was also reviewed. Collaboratively and iteratively, the task force reached consensus using a roundtable meeting, electronic mail, and conference calls. Main Results:Internal medicine-CCM–based fellowships have disparate program requirements compared to other internal medicine subspecialties and adult CCM fellowships. Differences between IM-CCM and pulmonary-CCM programs include the ratio of key clinical faculty to fellows and a requirement to perform 50 therapeutic bronchoscopies. Competency-based training was considered uniformly desirable for all CCM training pathways. Conclusions:The task force concluded that requesting competency-based training and minimizing variations in the requirements for IM-based CCM fellowship programs will facilitate effective CCM training for both programs and trainees.

Early goal-directed therapy for severe sepsis and septic shock: A living systematic review

Studies and meta-analyses conflict regarding the use of early goal-directed therapy (EGDT) for septic shock. We sought to clarify the conflict by performing a living systematic review and meta-regression. METHODS We performed a meta-analysis and explored heterogeneity with meta-regression. We conformed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and qualified strength of evidence with a Grading of Recommendations Assessment, Development and Evaluation profile. RESULTS Overall, EGDT did not significantly reduce mortality compared with usual care (relative risk, 0.85; 95% confidence interval, 0.67-1.08); however, heterogeneity was substantial (I2=64%; 95% confidence interval, 12%-85%). Illness severity did not correlate with mortality reduction; however, there were significant correlations with control rate mortality and the strategy employed by the control group. Benefit was confined to trials with a control mortality greater than 35%. Compared with monitoring of lactate clearance and central venous pressure, EGDT mortality was higher. CONCLUSION The benefit of EGDT is evident in populations with high mortality, in line with reported global mortality rates. In settings with low mortality the recent trials challenge the need for 6-hour goals; however, most patients in these trials met 3-hour resuscitation goals as defined by the Surviving Sepsis Campaign. In settings with higher mortality, EGDT or normalization of lactate/central venous pressure may be viable therapeutic options.

Pulmonary manifestations of the pre-engraftment syndrome after umbilical cord blood transplantation

Pre-engraftment syndrome (PES) is a condition occurring after umbilical cord blood transplantation (UCBT) characterized by fever and erythematous skin rash prior to neutrophil engraftment. We sought to determine the incidence and characterize the pulmonary manifestations of PES. A retrospective review of patients who underwent UCBT at the University of Kansas Medical Center over a 5-year period was performed. Data collected included patient baseline characteristics, presence of PES, pulmonary findings, treatments, and survival. Forty-four patients underwent UCBT with 22 of those patients developing PES. Full-intensity myeloablative conditioning regimen was found to be a risk factor for development of PES. Of those 22 patients, 13 had resting hypoxemia. The most common radiographic findings included diffuse ground glass opacities with pleural effusions. Fifteen patients with PES received corticosteroids, of which 12 had improvement in fevers and rash. These patients had a trend toward worse mortality than those not receiving corticosteroids. There was a nonsignificant trend toward worse survival in patients with PES and hypoxemia compared to those without hypoxemia. PES is a common complication following cord blood transplantation, with hypoxemia being present in over half of patients with PES. Hypoxemia with PES and treatment with corticosteroids may portend a worse prognosis.