American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock.

OBJECTIVES: The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine "Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock." DESIGN: Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006-2014). The PubMed/Medline/Embase literature (2006-14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. MEASUREMENTS AND MAIN RESULTS: The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. CONCLUSIONS: The major new recommendation in the 2014 update is consideration of institution-specific use of 1) a "recognition bundle" containing a trigger tool for rapid identification of patients with septic shock, 2) a "resuscitation and stabilization bundle" to help adherence to best practice principles, and 3) a "performance bundle" to identify and overcome perceived barriers to the pursuit of best practice principles.

Histone deacetylase inhibitors induce growth suppression and cell death in human rhabdomyosarcoma in vitro.

PURPOSE: A group of histone deacetylase inhibitors has been shown to be effective in suppressing the growth of a variety of transformed cell lines in vitro and in vivo. The effects of two of these agents, suberoylanilide hydroxamic acid (SAHA) and suberoyl-3-aminopyridineamide hydroxamic acid (pyroxamide), were investigated for their growth-suppressive effects on rhabdomyosarcoma (RMS) cells. EXPERIMENTAL DESIGN AND RESULTS: Dose-response experiments of two RMS cell lines, RD (embryonal) and RH30B (alveolar), were performed with SAHA (0.25-3.0 micro M) and pyroxamide (1.25-20.0 micro M). Both agents caused a dose-dependent decrease in viable cell number and an increase in percentage of dead cells over time. Exposure of the RMS cells to SAHA and pyroxamide resulted in an accumulation of acetylated histones with increasing doses by Western blot analysis. Additionally, there was an induction of p21/WAF1 at 15 and 24 h when the cells were cultured with SAHA (2.0 micro M) or pyroxamide (20.0 micro M), concentrations that were tested because they successfully induced inhibition of cell growth and initiated cell death in both RMS cell lines. An increase in nuclei with hypodiploid or sub-G(1) fraction was found by flow cytometry with increasing doses of both SAHA (0.25-3.0 micro M) and pyroxamide (1.25-20.0 micro M) over time. This finding is consistent with DNA fragmentation and cell death by apoptosis. CONCLUSIONS: SAHA and pyroxamide induce growth suppression and cell death in human RMS in vitro. Accumulation of acetylated histones and induction of p21/WAF1 expression are observed in cells exposed to either agent.

Mortality rates in pediatric septic shock with and without multiple organ system failure.

OBJECTIVES: To determine the current mortality rates for pediatric patients with septic shock and the frequency and outcome of associated multiple organ system failure. DESIGN: Retrospective chart review. SETTING: Multidisciplinary pediatric intensive care unit. PATIENTS: Children age 1 month to 21 yrs admitted to the pediatric intensive care unit from January 1, 1998, to December 31, 1999, with a diagnosis of septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A database of all admissions to the pediatric intensive care unit was queried, and cases with diagnoses of sepsis and septic shock were reviewed. The final study cohort consisted of 96 episodes of septic shock in 80 patients. Septic shock was defined as a clinical suspicion of sepsis manifested by hyperthermia or hypothermia accompanied by hypotension and/or alteration in perfusion. Multiple organ system failure was defined by established criteria. Data were analyzed by using Fisher's exact test. The overall mortality rate for the study cohort was 13.5%. There were differences in case mortality rates between patients requiring one inotropic agent (0%) and patients requiring multiple inotropic agents (42.9%), between oncology patients who had undergone bone marrow transplantation (38.5%) and oncology patients without bone marrow transplantation (5.5%), and between patients with multiple organ system failure (18.6%) and those without multiple organ system failure (0%); p <.05. There did not appear to be differences in the case mortality rates between oncology and nononcology patients or among patients with varying degrees of neutropenia. CONCLUSIONS: The mortality rate in pediatric septic shock is lower than has been previously reported. Oncologic illness in the absence of bone marrow transplantation does not appear to be associated with an increased mortality rate in children with septic shock. Bone marrow transplantation patients have an increased mortality rate compared with other patients with septic shock. Mortality from septic shock occurs most frequently in the context of multiple organ system failure.