Experimental endotoxemia as a model of the initial septic response affects the autonomic nervous system with profound cardiovascular sequelae. Whether the postsynaptic sympathoneural activity to the muscle vascular bed is altered in the early septic phase remains to be determined. The present study aimed to elucidate the early effects of LPS on muscle sympathetic nerve activity (MSNA) and cardiovascular regulation in healthy humans. Young, healthy volunteers randomly received either an LPS bolus (4 ng/kg body wt, n = 11) or placebo (saline; n = 7). Experimental baroreflex assessment (baseline measurements followed by infusion of vasoactive drugs nitroprusside/phenylephrine) was done prior to and 90 min following LPS or placebo challenge. MSNA, heart rate, blood pressure, and blood levels of catecholamines, TNF-alpha and IL-6 were measured sequentially. Endotoxin but not placebo-induced flu-like symptoms and elevated cytokine levels. In contrast to placebo, LPS significantly suppressed MSNA burst frequency 90 min after injection [mean +/- SE: 12.1 +/- 2.9 vs. 27.5 +/- 3.3 burst/min (post- vs. pre-LPS); P < 0.005] but increased heart rate [78.4 +/- 3.1 vs. 60.6 +/- 2.0 beats/min (post- vs. pre-LPS); P < 0.001]. Baseline blood pressure was not altered, but baroreflex testing demonstrated a blunted MSNA response and uncoupling of heart rate modulation to blood pressure changes in the endotoxin group. We conclude that endotoxin challenge in healthy humans has rapid suppressive effects on postsynaptic sympathetic nerve activity to the muscle vascular bed and alters baroreflex function which may contribute to the untoward cardiovascular effects of sepsis.

Severe acute cardiogenic pulmonary edema (ACPE) can successfully be treated with noninvasive pressure support ventilation (NIPSV) in a clinical setting. Whether prehospital NIPSV starting early at patients' home and being continued until hospital arrival is feasible and improves ACPE emergency care is examined in this study. End points of the study were oxygen saturation at hospital admission and clinical outcome. Twenty-three patients suffering from severe cardiac pulmonary edema with severe dyspnea, an oxygen saturation of less than 90% and basal rales were included in this controlled prospective randomized trial. All patients received standard medical treatment and 10 patients were additionally treated with NIPSV (pressure support level, 12 cmH2O; positive endexpiratory pressure, 5 cmH2O; FiO2, 0.6) whereas the other patients received oxygen (8 l/min) via Venturi face mask. Improvement in oxygen saturation was significantly faster in the NIPSV group and oxygen saturation was higher at the time of the hospital admission (NIPSV=97.3+/-0.8%; standard=89.5+/-2.7%, P=0.002). A trend toward higher troponin T levels was seen in the standard treatment group. The need for intensive care treatment did not differ, and one patient of each treatment group died in hospital. No complications were noted during the treatment with NIPSV. Prehospital NIPSV is feasible and able to improve emergency management of ACPE.

Objectives: This meta-analysis aimed to determine the effectiveness of prehospital continuous positive airway pressure (CPAP) or bilevel inspiratory positive airway pressure (BiPAP) in acute respiratory failure.Methods: Fourteen electronic databases and research registers were searched from inception to August 2013. Randomized or quasi-randomized controlled trials that reported mortality or intubation rate for prehospital CPAP or BiPAP were selected and compared to a relevant comparator in patients with acute respiratory failure. An aggregate data network meta-analysis was used to jointly estimate intervention effects relative to standard care. A network meta-analysis using a mixture of individual patient-level data and aggregate data was carried out to assess potential treatment effect modifiers.Results: Eight randomized and two quasi-randomized controlled trials (six CPAP, four BiPAP, sample sizes 23 to 207) were identified. The aggregate data network meta-analysis suggested that CPAP was the most effective treatment in terms of mortality (probability = 0.989) and intubation rate (probability = 0.639) and reduced both mortality (odds ratio [OR] = 0.41; 95% credible interval [CrI] = 0.20 to 0.77) and intubation rate (OR = 0.32; 95% CrI = 0.17 to 0.62), compared to standard care. The effect of BiPAP on mortality (OR = 1.94; 95% CrI = 0.65 to 6.14) and intubation rate (OR = 0.40; 95% CrI = 0.14 to 1.16) was uncertain. The network meta-analysis using individual patient-level data and aggregate data suggested that sex was a modifier of the effect of treatment on mortality. A cute respiratory failure is a common but lifethreatening medical emergency, especially in elderly patients with respiratory and cardiac diseases. [1][2][3] It is caused by a number of common cardiac or respiratory conditions, including heart failure, pneumonia, and exacerbation of chronic obstructive pulmonary disease. The definitive treatment of acute respiratory failure depends on the underlying cause, but patients often require prehospital treatment. At this point it is difficult to accurately determine the underlying cause, so prehospital treatment of acute respiratory failure often follows a common pathway, rather than being specific to the underlying cause. ConclusionsNoninvasive ventilation (NIV) can be used to treat acute respiratory failure. [4][5][6] It involves providing respiratory support through a tight-fitting mask that is usually applied around the patient's mouth and nose and may take the form of continuous positive airway pressure (CPAP) or bilevel inspiratory positive airway pressure (BiPAP), including noninvasive pressure support ventilation. It is normally used in the hospital, but it may be more effective if treatment is commenced prior to arrival.7 Prehospital NIV is considered in some guidelines, 8,9 but widespread use is limited by the need for additional training and equipment and may be informed by robust evidence of clinical effectiveness and cost-effectiveness.Prehospital NIV has been evaluated in a number o...