Mechanical ventilation in disaster situations: A new paradigm using the AGILITIES Score System.

BACKGROUND: The failure of life-critical systems such as mechanical ventilators in the wake of a pandemic or a disaster may result in death, and therefore, state and federal government agencies must have precautions in place to ensure availability, reliability, and predictability through comprehensive preparedness and response plans. METHODS: All 50 state emergency preparedness response plans were extensively examined for the attention given to the critically injured and ill patient population during a pandemic or mass casualty event. Public health authorities of each state were contacted as well. RESULTS: Nine of 51 state plans (17.6 percent) included a plan or committee for mechanical ventilation triage and management in a pandemic influenza event. All 51 state plans relied on the Centers for Disease Control and Prevention Flu Surge 2.0 spreadsheet to provide estimates for their influenza planning. In the absence of more specific guidance, the authors have developed and provided guidelines recommended for ventilator triage and the implementation of the AGILITIES Score in the event of a pandemic, mass casualty event, or other catastrophic disaster. CONCLUSIONS: The authors present and describe the AGILITIES Score Ventilator Triage System and provide related guidelines to be adopted uniformly by government agencies and hospitals. This scoring system and the set of guidelines are to be used in disaster settings, such as Hurricane Katrina, and are based on three key factors: relative health, duration of time on mechanical ventilation, and patients' use of resources during a disaster. For any event requiring large numbers of ventilators for patients, the United States is woefully unprepared. The deficiencies in this aspect of preparedness include (1) lack of accountability for physical ventilators, (2) lack of understanding with which healthcare professionals can safely operate these ventilators, (3) lack of understanding from where additional ventilator resources exist, and (4) a triage strategy to provide ventilator support to those patients with the greatest chances of survival.

Mechanical ventilation in disaster situations: a new paradigm using the AGILITIES Score System.

BACKGROUND: The failure of life-critical systems such as mechanical ventilators in the wake of a pandemic or a disaster may result in death, and therefore, state and federal government agencies must have precautions in place to ensure availability, reliability, and predictability through comprehensive preparedness and response plans. METHODS: All 50 state emergency preparedness response plans were extensively examined for the attention given to the critically injured and ill patient population during a pandemic or mass casualty event. Public health authorities of each state were contacted as well. RESULTS: Nine of 51 state plans (17.6 percent) included a plan or committee for mechanical ventilation triage and management in a pandemic influenza event. All 51 state plans relied on the Centers for Disease Control and Prevention Flu Surge 2.0 spreadsheet to provide estimates for their influenza planning. In the absence of more specific guidance, the authors have developed and provided guidelines recommended for ventilator triage and the implementation of the AGILITIES Score in the event of a pandemic, mass casualty event, or other catastrophic disaster. CONCLUSIONS: The authors present and describe the AGILITIES Score Ventilator Triage System and provide related guidelines to be adopted uniformly by government agencies and hospitals. This scoring system and the set ofguidelines are to be used iA disaster settings, such as Hurricane Katrina, and are based on three key factors: relative health, duration of time on mechanical ventilation, and patients' use of resources during a disaster. For any event requiring large numbers of ventilators for patients, the United States is woefully unprepared. The deficiencies in this aspect of preparedness include (1) lack of accountability for physical ventilators, (2) lack of understanding with which healthcare professionals can safely operate these ventilators, (3) lack of understanding from where additional ventilator resources exist, and (4) a triage strategy to provide ventilator support to those patients with the greatest chances of survival.

Design and synthesis of aryl ether inhibitors of the Bacillus anthracis enoyl-ACP reductase.

The problem of increasing bacterial resistance to the current generation of antibiotics is well documented. Known resistant pathogens such as methicillin-resistant Staphylococcus aureus are becoming more prevalent, while the potential exists for developing drug-resistant pathogens for use as bioweapons, such as Bacillus anthracis. The biphenyl ether antibacterial agent, triclosan, exhibits broad-spectrum activity by targeting the fatty acid biosynthetic pathway through inhibition of enoyl-acyl carrier protein reductase (ENR) and provides a potential scaffold for the development of new, broad-spectrum antibiotics. We used a structure-based approach to develop novel aryl ether analogues of triclosan that target ENR, the product of the fabI gene, from B. anthracis (BaENR). Structure-based design methods were used for the expansion of the compound series including X-ray crystal structure determination, molecular docking, and QSAR methods. Structural modifications were made to both phenyl rings of the 2-phenoxyphenyl core. A number of compounds exhibited improved potency against BaENR and increased efficacy against both the Sterne strain of B. anthracis and the methicillin-resistant strain of S. aureus. X-ray crystal structures of BaENR in complex with triclosan and two other compounds help explain the improved efficacy of the new compounds and suggest future rounds of optimization that might be used to improve their potency.

The neurotoxicity of tissue plasminogen activator?

Tissue plasminogen activator (tPA), a fibrin specific activator for the conversion of plasminogen to plasmin, stimulates thrombolysis and rescues ischemic brain by restoring blood flow. However, emerging data suggests that under some conditions, both tPA and plasmin, which are broad spectrum protease enzymes, are potentially neurotoxic if they reach the extracellular space. Animal models suggest that in severe ischemia with injury to the blood brain barrier (BBB) there is injury attributed to the protease effects of this exogenous tPA. Besides clot lysis per se, tPA may have pleiotropic actions in the brain, including direct vasoactivity, cleaveage of the N-methyl-D-aspartate (NMDA) NR1 subunit, amplification of intracellular Ca++ conductance, and activation of other extracellular proteases from the matrix metalloproteinase (MMP) family, e.g. MMP-9. These effects may increase excitotoxicity, further damage the BBB, and worsen edema and cerebral hemorrhage. If tPA is effective and reverses ischemia promptly, the BBB remains intact and exogenous tPA remains within the vascular space. If tPA is ineffective and ischemia is prolonged, there is the risk that exogenous tPA will injure both the neurovascular unit and the brain. Methods of neuroprotection, which prevent tPA toxicity or additional mechanical means to open cerebral vessels, are now needed.