Immediate Norepinephrine in Endotoxic Shock: Effects on Regional and Microcirculatory Flow.

OBJECTIVES: To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock. DESIGN: Animal experimental study. SETTING: University translational research laboratory. SUBJECTS: Fifteen Landrace pigs. INTERVENTIONS: Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance. MEASUREMENTS AND MAIN RESULTS: Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively). CONCLUSIONS: In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.

Smart Tree: An Architectural, Greening and ICT Multidisciplinary Approach to Smart Campus Environments.

At present, climate change, pollution, and uncontrolled urbanism threaten not only natural ecosystems, but also the urban environment. Approaches to mitigate these challenges and able to provide an alternative for the use of the space are deemed to be multidisciplinary, combining architecture, vegetation integration, circular economy and information and communications technologies (ICT). University campuses are a key scenario to evaluate such solutions as their student and research community is intrinsically willing to support these experiences and provide a wide knowledge on the fields necessary for their design and implementation. However, the creation of areas combining usability and sustainability is commonly lacking a multidisciplinary approach combining all these different perspectives. Hence, the present work aims to overcome this limitation by the development of a novel integrated approach for campus spaces for co-working and leisure, namely a "Smart Tree", where novel architecture, furniture design, flora integration, environmental sensoring and communications join together. To this end, a survey of the literature is provided, covering related approaches as well as general principles behind them. From this, the general requirements and constraints for the development of the Smart Tree area are identified, establishing the main interactions between the architecture, greening and ICT perspectives. Such requirements guide the proposed system design and implementation, whose impact on the environment is analyzed. Finally, the research challenges and lessons learned for their development are identified in order to support future works.

Amputation in crush syndrome: A case report.

INTRODUCTION: Crush syndrome (CS) is a condition with a high morbidity and mortality due to severe electrolyte disorders, circulatory dysfunction and multiple organ failure, secondary to severe rhabdomyolysis and reperfusion injuries. There is controversy about the role of fasciotomy in the treatment of compartment syndromes due to crush injuries and it is still unknown if early amputation has patient-centered benefits. CASE PRESENTATION: This is a 29-year-old patient whose lower body was trapped for 50 h under a 40-meter landslide. Upon admission the left thigh was edematous and painful. Laboratories revealed a creatinine of 1.58 mg/dL, hyperkalemia, metabolic acidosis, hyperlactatemia and creatinine phosphokinase (CPK) of 88,700 U/L, suggesting CS. Despite fluid and bicarbonate infusion his renal function worsened, CPK rose and left thigh became more tense, so a fasciotomy was performed. He developed a distributive shock refractory to vasopressors, steroids and methylene blue so amputation was proposed. Two hours after amputation the vasopressor support was nearly withdrawn. DISCUSSION: This case suggests a potential benefit of amputation in patients with CS and progressive deterioration despite aggressive resuscitation. It also invites to think if this is a decision that should be considered before the establishment or in the initial stages of the syndrome, even if the viability of the extremity is still questionable. CONCLUSION: The presence of risk factors for poor prognosis can favor amputation despite the apparent viability of the limb and the morbidity of losing an extremity.

Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O2 extraction during septic shock.

Derangements of microvascular blood flow distribution might contribute to disturbing O2 extraction by peripheral tissues. We evaluated the dynamic relationships between the mesenteric O2 extraction ratio ([Formula: see text]) and the heterogeneity of microvascular blood flow at the gut and sublingual mucosa during the development and resuscitation of septic shock in a swine model of fecal peritonitis. Jejunal-villi and sublingual microcirculation were evaluated using a portable intravital-microscopy technique. Simultaneously, we obtained arterial, mixed-venous, and mesenteric blood gases, and jejunal-tonometric measurements. During resuscitation, pigs were randomly allocated to a fixed dose of dobutamine (5 µg·kg-1·min-1) or placebo while three sham models with identical monitoring served as controls. At the time of shock, we observed a significant decreased proportion of perfused intestinal-villi (villi-PPV) and sublingual percentage of perfused small vessels (SL-PPV), paralleling an increase in [Formula: see text] in both dobutamine and placebo groups. After starting resuscitation, villi-PPV and SL-PPV significantly increased in the dobutamine group with subsequent improvement of functional capillary density, whereas [Formula: see text] exhibited a corresponding significant decrease (repeated-measures ANOVA, P = 0.02 and P = 0.04 for time × group interactions and intergroup differences for villi-PPV and [Formula: see text], respectively). Variations in villi-PPV were paralleled by variations in [Formula: see text] (R2 = 0.88, P < 0.001) and these, in turn, by mesenteric lactate changes (R2 = 0.86, P < 0.001). There were no significant differences in cardiac output and systemic O2 delivery throughout the experiment. In conclusion, dynamic changes in microvascular blood flow heterogeneity at jejunal mucosa are closely related to the mesenteric O2 extraction ratio, suggesting a crucial role for microvascular blood flow distribution on O2 uptake during development and resuscitation from septic shock.NEW & NOTEWORTHY Our observations suggest that dynamic changes in the heterogeneity of microvascular blood flow at the gut mucosa are closely related to mesenteric O2 extraction, thus supporting the role of decreasing functional capillary density and increased intercapillary distances on alterations of O2 uptake during development and resuscitation from septic shock. Addition of a low-fixed dose of dobutamine might reverse such flow heterogeneity, improving microcirculatory flow distribution and tissue O2 consumption.