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Objective Hemodynamic resuscitation is considered a cornerstone of the initial treatment of septic shock. However, there is growing concern about its side effects. Our objective was to assess the relationship between fluid administration and norepinephrine infusion and the development of lung injury. Design Randomized in vivo study in rabbits. Setting University animal research laboratory. Patients Eighteen New Zealand rabbits. Control group (SHAM, n=6), Sepsis group with or without hemodynamic resuscitation (ETX-R, n=6; ETX-NR, n=6). Interventions Sepsis was induced by intravenous lipopolysaccharide administration and animals were followed-up for 4h. Hemodynamic resuscitation with Ringer lactate (20mL·kg−1) was administered and later norepinephrine was initiated 3h after sepsis induction. At the end, the left lung was excised. Main variables of interestAn indwelling arterial catheter and an esophageal Doppler were placed. Lung mechanics were monitored with side stream spirometry. Lung damage was analyzed by histopathological examination. Results The SHAM group did not show hemodynamic or respiratory changes. Lipopolysaccharide administration aimed an increase in cardiac output and arterial hypotension. In the ETX-NR group, animals remained hypotensive until the end of the experiment. Resuscitation with fluids and norepinephrine reversed arterial hypotension. Compared to the ETX-NR group, the remaining lung of the ETX-R group showed greater accumulation of neutrophils and reactive type-II pneumocytes, thicker alveolar wall, alveolar hemorrhage and non-aerated pulmonary areas. Lung injury score was larger in the ETX-R group. Conclusions In our experimental study, following a strategy with bolus fluids and late norepinephrine used in the early phase of endotoxic septic shock has a negative influence on the development of lung injury. (AU)

Objetivo La resucitación hemodinámica es considerada piedra angular en el tratamiento inicial del shock séptico. Sin embargo, existe creciente preocupación sobre sus efectos indeseables. Nuestro objetivo fue evaluar la relación entre la administración de fluidos e infusión de noradrenalina y el desarrollo de lesión pulmonar. Diseño Estudio aleatorizado en animales vivos. Ámbito Laboratorio universitario de investigación. Participantes Dieciocho conejos de raza New Zealand White. Grupo control (SHAM, n=6), grupo séptico con o sin resucitación hemodinámica (ETX-R, n=6; ETX-NR, n=6). Intervención La sepsis fue inducida tras administración intravenosa de lipopolisacárido, y los animales fueron seguidos durante 4h. La resucitación hemodinámica mediante suero Ringer lactato (20ml·kg-1) y posterior noradrenalina fue iniciada a las 3h de ser inducida la sepsis. Al final del estudio, el pulmón izquierdo fue extraído. Principales variables de interés Fueron empleados catéter arterial y doppler esofágico. La mecánica pulmonar fue monitorizada con sensor de flujo. El daño pulmonar fue analizado mediante examen histopatológico. Resultados El grupo control no mostró cambios hemodinámicos ni respiratorios. La administración del lipopolisacárido produjo un incremento del gasto cardíaco e hipotensión arterial. En el grupo ETX-NR, los animales permanecieron hipotensos hasta el final del estudio. La resucitación con fluidos y noradrenalina revirtió la hipotensión arterial. Comparados con el grupo ETX-NR, en el grupo ETX-R el estudio histopatológico mostró mayor acumulación de neutrófilos, así como mayor presencia de neumocitos activados tipo II, engrosamiento de la pared alveolar, hemorragia alveolar y zonas pulmonares no aireadas. La escala final de daño pulmonar fue mayor en el grupo ETX-R. Conclusiones En nuestro estudio experimental ... (AU)

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OBJECTIVE: Hemodynamic resuscitation is considered a cornerstone of the initial treatment of septic shock. However, there is growing concern about its side effects. Our objective was to assess the relationship between fluid administration and norepinephrine infusion and the development of lung injury. DESIGN: Randomized in vivo study in rabbits. SETTING: University animal research laboratory. PATIENTS: Eighteen New Zealand rabbits. Control group (SHAM, n=6), Sepsis group with or without hemodynamic resuscitation (ETX-R, n=6; ETX-NR, n=6). INTERVENTIONS: Sepsis was induced by intravenous lipopolysaccharide administration and animals were followed-up for 4h. Hemodynamic resuscitation with Ringer lactate (20mL·kg-1) was administered and later norepinephrine was initiated 3h after sepsis induction. At the end, the left lung was excised. MAIN VARIABLES OF INTEREST: An indwelling arterial catheter and an esophageal Doppler were placed. Lung mechanics were monitored with side stream spirometry. Lung damage was analyzed by histopathological examination. RESULTS: The SHAM group did not show hemodynamic or respiratory changes. Lipopolysaccharide administration aimed an increase in cardiac output and arterial hypotension. In the ETX-NR group, animals remained hypotensive until the end of the experiment. Resuscitation with fluids and norepinephrine reversed arterial hypotension. Compared to the ETX-NR group, the remaining lung of the ETX-R group showed greater accumulation of neutrophils and reactive type-II pneumocytes, thicker alveolar wall, alveolar hemorrhage and non-aerated pulmonary areas. Lung injury score was larger in the ETX-R group. CONCLUSIONS: In our experimental study, following a strategy with bolus fluids and late norepinephrine used in the early phase of endotoxic septic shock has a negative influence on the development of lung injury.

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OBJECTIVE: Hemodynamic resuscitation is considered a cornerstone of the initial treatment of septic shock. However, there is growing concern about its side effects. Our objective was to assess the relationship between fluid administration and norepinephrine infusion and the development of lung injury. DESIGN: Randomized in vivo study in rabbits. SETTING: University animal research laboratory. PATIENTS: Eighteen New Zealand rabbits. Control group (SHAM, n=6), Sepsis group with or without hemodynamic resuscitation (ETX-R, n=6; ETX-NR, n=6). INTERVENTIONS: Sepsis was induced by intravenous lipopolysaccharide administration and animals were followed-up for 4h. Hemodynamic resuscitation with Ringer lactate (20mL·kg-1) was administered and later norepinephrine was initiated 3h after sepsis induction. At the end, the left lung was excised. MAIN VARIABLES OF INTEREST: An indwelling arterial catheter and an esophageal Doppler were placed. Lung mechanics were monitored with side stream spirometry. Lung damage was analyzed by histopathological examination. RESULTS: The SHAM group did not show hemodynamic or respiratory changes. Lipopolysaccharide administration aimed an increase in cardiac output and arterial hypotension. In the ETX-NR group, animals remained hypotensive until the end of the experiment. Resuscitation with fluids and norepinephrine reversed arterial hypotension. Compared to the ETX-NR group, the remaining lung of the ETX-R group showed greater accumulation of neutrophils and reactive type-II pneumocytes, thicker alveolar wall, alveolar hemorrhage and non-aerated pulmonary areas. Lung injury score was larger in the ETX-R group. CONCLUSIONS: In our experimental study, following a strategy with bolus fluids and late norepinephrine used in the early phase of endotoxic septic shock has a negative influence on the development of lung injury.

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BACKGROUND.: Dynamic arterial elastance (Ea dyn ), the relationship between pulse pressure variation (PPV) and stroke volume variation (SVV), has been suggested as a functional assessment of arterial load. The aim of this study was to evaluate the impact of arterial load changes during acute pharmacological changes, fluid administration, and haemorrhage on Ea dyn . METHODS.: Eighteen anaesthetized, mechanically ventilated New Zealand rabbits were studied. Arterial load changes were induced by phenylephrine ( n =9) or nitroprusside ( n =9). Thereafter, animals received a fluid bolus (10 ml kg -1 ), followed by stepwise bleeding (blood loss: 15 ml kg -1 ). The influence of arterial load and cardiac variables on PPV, SVV, and Ea dyn was analysed using a linear mixed-effects model analysis. RESULTS.: After phenylephrine infusion, mean ( sd ) Ea dyn decreased from 0.89 (0.14) to 0.49 (0.12), P <0.001; whereas after administration of nitroprusside, Ea dyn increased from 0.80 (0.23) to 1.28 (0.21), P <0.0001. Overall, the fluid bolus decreased Ea dyn [from 0.89 (0.44) to 0.73 (0.35); P <0.01], and haemorrhage increased it [from 0.78 (0.23) to 0.95 (0.26), P =0.03]. Both PPV and SVV were associated with similar arterial factors (effective arterial elastance, arterial compliance, and resistance) and heart rate. Furthermore, PPV was also related to the acceleration and peak velocity of aortic blood flow. Both arterial and cardiac factors contributed to the evolution of Ea dyn throughout the experiment. CONCLUSIONS.: Acute modifications of arterial load induced significant changes on Ea dyn ; vasodilatation increased Ea dyn , whereas vasoconstriction decreased it. The Ea dyn was associated with both arterial load and cardiac factors, suggesting that Ea dyn should be more properly considered as a ventriculo-arterial coupling index.

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OBJECTIVE: A study is made of the influence of preemptive hemodynamic intervention restricting fluid administration upon the development of oleic acid-induced lung injury. DESIGN: A randomized in vivo study in rabbits was carried out. SETTING: University research laboratory. Subjects: Sixteen anesthetized, mechanically ventilated rabbits. VARIABLES: Hemodynamic measurements obtained by transesophageal Doppler signal. Respiratory mechanics computed by a least square fitting method. Lung edema assessed by the ratio of wet weight to dry weight of the right lung. Histological examination of the left lung. INTERVENTIONS: Animals were randomly assigned to either the early protective lung strategy (EPLS) (n=8) or the early protective hemodynamic strategy (EPHS) (n=8). In both groups, lung injury was induced by the intravenous infusion of oleic acid (OA) (0.133mlkg−1h−1 for 2h). At the same time, the EPLS group received 15mlkg−1h−1 of Ringer lactate solution, while the EPHS group received 30mlkg−1h−1. Measurements were obtained at baseline and 1 and 2h after starting OA infusion. RESULTS: After 2h, the cardiac index decreased in the EPLS group (p < 0.05), whereas in the EPHS group it remained unchanged. Lung compliance decreased significantly only in the EPHS group (p < 0.05). Lung edema was greater in the EPHS group (p < 0.05). Histological damage proved similar in both groups (p = 0.4). CONCLUSIONS: In this experimental model of early lung injury, lung edema progression was attenuated by preemptively restricting the administration of fluids

OBJETIVO: Conocer cómo influye una intervención hemodinámica preventiva basada en la restricción de fluidos sobre el desarrollo de la lesión pulmonar inducida por la administración de ácido oleico. DISEÑO: Estudio aleatorizado en animales vivos. Lugar: Laboratorio universitario de investigación experimental. VARIABLES: Mecánica respiratoria (método de los mínimos cuadrados), medidas hemodinámicas (doppler esofágico), estimación del edema pulmonar (relación peso húmedo/seco del pulmón derecho) y daño histológico del pulmón izquierdo. INTERVENCIONES: Ocho animales fueron asignados a un grupo con una estrategia protectora pulmonar (EPP), y otros 8 a otro grupo con una estrategia protectora hemodinámica (EPH). En ambos grupos la lesión pulmonar se desencadenó mediante la administración intravenosa de ácido oleico (0,133mL/kg−1/h−1 durante 2h), recibiendo simultáneamente los animales del grupo EPP 15mL/kg−1/h−1 de Ringer Lactato y los del grupo EPH 30mLKg−1h−1. Se obtuvieron medidas basales, a la hora y a las 2h. RESULTADOS: Transcurridas las 2h de experimento el índice cardiaco permaneció estable en el grupo EPH, pero disminuyó en el grupo EPP (p < 0,05). Por el contrario, la distensibilidad pulmonar disminuyó significativamente solo en el grupo EPH (p < 0,05), en el cual el edema pulmonar estimado mediante la relación peso húmedo/seco del pulmón derecho fue mayor (p < 0,05). El daño histológico fue similar en ambos grupos (p = 0,4). CONCLUSIONES: En este modelo experimental de lesión pulmonar aguda en fase inicial, la formación del edema pulmonar fue atenuada por la restricción preventiva en la administración de fluidos

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OBJECTIVE: A study is made of the influence of preemptive hemodynamic intervention restricting fluid administration upon the development of oleic acid-induced lung injury. DESIGN: A randomized in vivo study in rabbits was carried out. SETTING: University research laboratory. SUBJECTS: Sixteen anesthetized, mechanically ventilated rabbits. VARIABLES: Hemodynamic measurements obtained by transesophageal Doppler signal. Respiratory mechanics computed by a least square fitting method. Lung edema assessed by the ratio of wet weight to dry weight of the right lung. Histological examination of the left lung. INTERVENTIONS: Animals were randomly assigned to either the early protective lung strategy (EPLS) (n=8) or the early protective hemodynamic strategy (EPHS) (n=8). In both groups, lung injury was induced by the intravenous infusion of oleic acid (OA) (0.133mlkg-1h-1 for 2h). At the same time, the EPLS group received 15mlkg-1h-1 of Ringer lactate solution, while the EPHS group received 30mlkg-1h-1. Measurements were obtained at baseline and 1 and 2h after starting OA infusion. RESULTS: After 2h, the cardiac index decreased in the EPLS group (p<0.05), whereas in the EPHS group it remained unchanged. Lung compliance decreased significantly only in the EPHS group (p<0.05). Lung edema was greater in the EPHS group (p<0.05). Histological damage proved similar in both groups (p=0.4). CONCLUSIONS: In this experimental model of early lung injury, lung edema progression was attenuated by preemptively restricting the administration of fluids.

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