Mark A. Mazer

Impact of regular collaboration between infectious diseases and critical care practitioners on antimicrobial utilization and patient outcome.

Objective:Antimicrobial stewardship programs have been shown to help reduce the use of unnecessary antimicrobial agents in the hospital setting. To date, there has been very little data focusing on high-use areas, such as the medical ICU. A prospective intervention was done to assess guideline compliance, antimicrobial expenditure, and healthcare cost when an infectious disease fellow interacts regularly with the medical ICU team. Design:A 3-month retrospective chart review was followed by a 3-month prospective intervention the following year. Two hundred forty-six total charts were reviewed to assess generally accepted guideline compliance, demographics, and microbiologic results. Setting:Twenty-four-bed medical ICU at an 861-bed tertiary care, university teaching hospital in North Carolina. Subjects:Patients receiving antibiotics in the medical ICU. Intervention:During the intervention period, the infectious disease fellow reviewed the charts, including physician notes and microbiology data, and discussed antimicrobial use with the medical ICU team. Measurements and Main Results:Antimicrobial use, treatment duration, Acute Physiology and Chronic Health Evaluation II scores, length of stay, mechanical ventilation days, and mortality rates were compared during the two periods. Results:No baseline statistically significant differences in the two groups were noted (i.e., age, gender, race, or Acute Physiology and Chronic Healthcare Evaluation II scores). Indications for antibiotics included healthcare-associated (53%) and community-acquired pneumonias (17%). Significant reductions were seen in extended-spectrum penicillins (p = 0.0080), carbapenems (p = 0.0013), vancomycin (p = 0.0040), and metronidazole (p = 0.0004) following the intervention. Antimicrobial modification led to an increase in narrow-spectrum penicillins (p = 0.0322). The intervention group had a significantly lower rate of treatments that did not correspond to guidelines (p < 0.0001). There was a reduction in mechanical ventilation days (p = 0.0053), length of stay (p = 0.0188), and hospital mortality (p = 0.0367). The annual calculated healthcare savings was

The public's attitude and perception concerning witnessed cardiopulmonary resuscitation.

89,944 in early antibiotic cessation alone. Conclusion:Active communication with an infectious disease practitioner can significantly reduce medical ICU antibiotic overuse by earlier modification or cessation of antibiotics without increasing mortality. This in turn can reduce healthcare costs, foster prodigious education, and strengthen relations between the subspecialties.

Low Levels of NF-κB/p65 Mark Anergic CD4+ T Cells and Correlate with Disease Severity in Sarcoidosis

Objective:For healthcare providers, witnessed cardiopulmonary resuscitation (CPR) is controversial. However, little is known about the public’s stance on this issue. This study was performed to develop insight concerning the general public’s thoughts about witnessed CPR. Design:A random telephone survey. Setting:Rural southwest Pennsylvania. Subjects:Four hundred and eight respondents, ≥18 yrs old, residing in Conemaugh Health System’s Memorial Medical Center’s service area. Interventions:Demographic information was gathered concerning the respondents, who rated their level of agreement with questions concerning witnessed resuscitation. Measurements and Main Results:Of the respondents, 49.3% desired to be present while CPR is performed on a loved one. Respondents desiring CPR were more apt to believe that significant others have a right to be present during CPR (p = .010) and want significant others present with them while undergoing CPR than those declining CPR (p < .001). Respondents desiring CPR felt more strongly that the presence of family or friends during CPR would benefit the patient (p = .022). The desire to be present in the room with a loved one during CPR did not reach statistical significance (p = .275) between the two groups, nor did the belief that that being present would benefit family and friends (p = .093). Of the respondents, 43% believed that the physician should have the most authority in making decisions about witnessed resuscitation, 40% believed that the patient should have the most authority, and 17% believed that family and friends should have the most authority (p < .001). Those who believed that family and friends should have the most authority were more favorable toward witnessed resuscitation than were those who believed that either the patient or the physician should have the most authority. Conclusions:This study offers insights into the public’s attitude concerning witnessed resuscitation. A large segment of the population desires the presence of significant others during CPR and conversely want to be with loved ones during CPR. Further studies should investigate the public’s attitude in more diverse settings, and formal programs to accommodate those who wish to remain together during CPR should be developed.

The Infusion of Opioids During Terminal Withdrawal of Mechanical Ventilation in the Medical Intensive Care Unit

ABSTRACT T lymphocytes from patients with sarcoidosis respond weakly when stimulated with mitogen or antigen. However, the mechanisms responsible for this anergy are not fully understood. Here, we investigated the protein levels of nuclear transcription factor NF-κB (p50, p65, and p105), IκBα (inhibitor of NF-κB), T-cell receptor (TCR) CD3ζ-chain, tyrosine kinase p56LCK, and nuclear factor of activated T cells c2 (NF-ATc2) in peripheral blood CD4+ T cells from patients with sarcoidosis. Baseline expression of p65 in these lymphocytes was reduced in 50% of patients. The reduced levels of p65 in sarcoid CD4+ T cells concurred with decreased levels of p50, p105, CD3ζ, p56LCK, IκBα, and NF-ATc2. Polyclonal stimulation of NF-κB-deficient sarcoid T cells resulted in reduced expression of CD69 and CD154, decreased proliferation, and cytokine (i.e., interleukin 2 [IL-2] and gamma interferon [IFN-γ]) production. The clinical significance of these findings is suggested by the association between low p65 levels and the development of more severe and active sarcoidosis. Although correlative, our results support a model in which multiple intrinsic signaling defects contribute to peripheral T-cell anergy and the persistence of chronic inflammation in sarcoidosis.

Expanding the pool of healthcare providers to perform penicillin skin testing in the ICU.

CONTEXT Most deaths in intensive care units occur after limitation or withdrawal of life-sustaining therapies. Often these patients require opioids to assuage suffering; yet, little has been documented concerning their use in the medical intensive care unit. OBJECTIVES To determine the dose and factors influencing the use of opioids in patients undergoing terminal withdrawal of mechanical ventilation in this setting. METHODS Data were prospectively collected from 74 consecutive patients expected to die soon after extubation. The doses of morphine, effect on time to death, and relation of dose to diagnostic categories were analyzed. RESULTS The mean (±standard deviation) dose of morphine given to patients during the last hour of mechanical ventilation was 5.3mg/hour. Patients dying after extubation received 10.6 mg/hour just before death. Immediately before extubation, the dose correlated directly with chronic medical opioid use and sepsis with respiratory failure and inversely with coma after cardiopulmonary resuscitation or a primary neurological event. After terminal extubation, the final morphine dose correlated directly with the presence of sepsis with respiratory failure and chronic pulmonary disease. The mean time to death after terminal extubation was 152.7 ± 229.5 minutes without correlation with premorbid diagnoses. After extubation, each 1mg/hour increment of morphine infused during the last hour of life was associated with a delay of death by 7.9 minutes (P = 0.011). CONCLUSION Premorbid conditions may influence the dose of morphine given to patients undergoing terminal withdrawal of mechanical ventilation. Higher doses of morphine are associated with a longer time to death.

United States—Academic Medicine: Where Are We Going?

Dear Editor, Penicillin skin testing (PST) is imperative in intensive care unit (ICU) patients urgently in need of appropriate antibiotics [1]. We aimed to: determine the prevalence of penicillin allergy in a sample of ICU patients with a penicillin allergy label; assess the negative predictive value (NPV) of PST; and assess whether healthcare providers of various disciplines can safely perform PST. From March 2012 through September 2013, a multi-disciplinary PST educational project was carried out under an Institutional Review Board approved protocol. The critical care team contacted a trained specialist (R.H.R.) when patients had a penicillin allergy label with uncertain/unknown history or prior IgEmediated reaction [2]. Excluded were those with non-IgE mediated prior reaction(s), history of exfoliative or over-reactive skin conditions, anaphylaxis \4 weeks prior, and those not requested by the critical care team. R.H.R. trained providers in PST administration, which consisted of one-on-one didactic reviews in preparing for anaphylaxis, reagent application, and interpretation according to guidelines [2]. The preliminary epicutaneous puncture testing was followed by an intradermal injection (if there lacked a wheal C3 mm; Fig. 1) using: a benzylpenicilloyl major determinant molecule, a penicillin G potassium minor determinant at 10,000 units/cc, histamine 1 mg/mL, and normal saline. A negative PST was confirmed with a single 250-mg oral dose of penicillin VK. If appropriate, the patient was transitioned to a beta-lactam and monitored for 24 h to estimate the NPV. During the 19-month period, 579 (12.2 %) of our 4,729 ICU patients had a penicillin allergy label, of which 100 (17.3 %) underwent PST by various healthcare providers, including 55 physicians, 20 medical students, 20 nurses, and 5 pharmacists (Table 1). All 100 patients had a negative reaction to the PST, oral challenge, and beta-lactam transition, yielding a NPV of 100 %. Penicillin allergy alone has been associated with increased ICU admissions and length of stay [3]. With increasing resistance, alternative non-beta-lactams may no longer be an option. Since ICUs accounts for 10–25 % of healthcare costs, ICUs are an appropriate venue to enact safe and effective measures to impact these costs [4, 5]. No prior study has illustrated the effectiveness and safety of PST when performed by a multidisciplinary pool of ICU providers. Also, the concept of training nonallergists to perform and interpret PSTs is novel. The lack of true penicillin allergies may relate to the large percentage (45 %) of our patients not knowing the specifics of their prior reaction. It may be safer to perform PST rather than assume a prior unknown/uncertain reaction was non-IgE-mediated and directly challenge them. Our intervention was a single-site study and results may not be generalizable. Including more from the 579 patients may affect our results. In conclusion, multidisciplinary healthcare providers can safely and effectively perform PST. The incidence of penicillin allergy in ICU patients is substantially lower than the history or medical record would indicate. PST plays an essential role in ICU antimicrobial stewardship and is an effective strategy to help control antimicrobial resistance and rising healthcare costs.

456: INFLUENZA B-INDUCED CATASTROPHIC HYPERCOAGULABLE RESPONSE

Critical care providers in the United States are frustrated by their participation in the most costly medical delivery system in the world, nonetheless plagued by a dismal return on investment in terms of value. The current pace of increasing cost, without budgetary restraint and without adequate guarantee of quality, is a recipe for economic disaster. However, given proper direction and stewardship, the American medical system is capable of providing high value, cost effective healthcare.

Obesity and Weaning from Mechanical Ventilation—An Exploratory Study

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: Seasonal influenza comprises of an acute respiratory illness caused by influenza A and B viruses. While there have been reports of influenza A causing dysfunctional coagulation, there is far less clinical and epidemiologic data regarding influenza B and its complications. Visseren et al demonstrated procoagulant activity of endothelial cells following exposure to respiratory viruses including influenza. Here, we present an unusual case of a patient with influenza B resulting in a catastrophic hypercoagulable response. Methods: A 70 year-old morbidly obese female with a significant medical history of systolic heart failure, hypertension, diabetes and oxygen dependent chronic respiratory failure presented to the emergency department with shortness of breath, hypoglycemia and hypoxemia. Despite aggressive resuscitation with crystalloids, dextrose and non-invasive ventilation, she required intubation and mechanical ventilation for hypercarbic and hypoxic respiratory failure. Laboratory values were significant for leukocytosis, hyperkalemia and acute kidney injury as well as profound hypoglycemia and lactic acidosis. Echocardiogram revealed elevated right ventricular systolic pressures with right apical multilobular echodensities consisting with thrombus. Intravenous heparin was initiated, in addition to broad-spectrum antibiotics. Upper and lower extremity dopplers revealed large clot burden within the right upper extremity, left popliteal vein and left peroneal vein. Rapid molecular viral panel confirmed influenza B positivity while lupus anticoagulant, anticardiolipin and β2 glycoprotein were negative. Chest imaging showed multifocal bilateral airspace opacities with concern for acute respiratory distress syndrome. Given patient’s poor prognosis, her family pursued comfort measures and patient passed away. Autopsy confirmed multiple concomitant thromboemboli with exquisite clot burden including thromboembolus of left pulmonary artery and biventricular thrombi. Results: Aggressive inflammation can occur leading to dysfunctional coagulation in pathogenic influenza. In active infectious states, cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α can be released causing activation of endothelial cells, platelets and modulate macrophage survival resulting in promoting thrombus formation. To our knowledge, this is the first reported case of influenza B infection precluding catastrophic systemic thromboembolisms.

Addition of rifampin to vancomycin for the treatment of pneumonias due to methicillin-resistant Staphylococcus aureus: Caveat emptor

Introduction: Obesity is associated with increased risk of hypercapnic respiratory failure, prolonged duration on mechanical ventilation, and extended weaning periods. Objective: Pilot study to determine whether morbidly obese adult tracheotomized subjects (body mass index [BMI] ⩾ 40) can be more efficiently weaned from the ventilator by optimizing their positive end-expiratory pressure (PEEP) using either an esophageal balloon or the best achieved static effective compliance. Methods: We randomly assigned 25 morbidly obese adult tracheotomized subjects (median [interquartile range] BMI 53.4 [26.4]; range 40.4-113.8) to 1 of 2 methods of setting PEEP; using either titration guided by esophageal balloon to overcome negative transpulmonary pressure (Ptp) (goal Ptp 0-5 cmH2O) (ESO group) or titration to maximize static effective lung compliance (Cstat group). Our outcomes of interest were number of subjects weaned by day 30 and time to wean. Results: At day 30, there was no significant difference in percentage of subjects weaned. 8/13 subjects (62%) in the ESO Group were weaned vs. 9/12(75%) in the Cstat Group (P = 0.67). Among the 17 subjects who weaned, median time to ventilator liberation was significantly shorter in the ESO group: 3.5 days vs Cstat group 14 days (P = .01). Optimal PEEP in the ESO and Cstat groups was similar (ESO mean ± SD = 26.5 ± 5.7 cmH2O and Cstat 24.2 ± 7 cmH2O (P = .38). Conclusions: Optimization of PEEP using esophageal balloon to achieve positive transpulmonary pressure did not change the proportion of patients weaned. Among patients who weaned, use of the esophageal balloon resulted in faster liberation from mechanical ventilation. There were no adverse consequences of the high PEEP (mean 25.4; range 13-37 cmH2O) used in our study. The study was approved by the Institutional Review Board at our institution (UMCIRB#10-0343) and registered with clinicaltrials.gov (NCT02323009).