Hemodynamic resuscitation with fluids bolus and norepinephrine increases severity of lung damage in an experimental model of septic shock / La resucitación hemodinámica con bolos de fluidos y noradrenalina incrementa la severidad del daño pulmonar en un modelo experimental de shock séptico

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)

Hemodynamic resuscitation with fluids bolus and norepinephrine increases severity of lung damage in an experimental model of septic shock.

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.

Hemodynamic resuscitation with fluids bolus and norepinephrine increases severity of lung damage in an experimental model of septic shock.

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.

Shock séptico / Septic shock

El shock séptico es un estado de hipoperfusión tisular en el contexto de un síndrome de respuesta inflamatoria sistémica, caracterizado clínicamente por vasodilatación excesiva y el requerimiento de agentes presores para mantener la presión de perfusión de los órganos. La típica respuesta cardiovascular hiperdinámica no está presente en todos los enfermos, por lo que su presencia o ausencia no debe usarse para el diagnóstico del shock séptico. El tratamiento exige la normalización de la volemia y la administración de agentes inotropos para normalizar el gasto cardíaco si se encuentra bajo, y aumentar la presión de perfusión de los tejidos. El tratamiento debe ser guiado por una adecuada monitorización. Es preferible el uso de técnicas que permiten valorar la precarga del ventrículo derecho, más que mediciones aisladas de presiones de llenado ventricular (que no se relacionan con la precarga ni con la respuesta del individuo a la sobrecarga de fluidos). Recientemente, se ha puesto de manifiesto que la variación de la presión de pulso está en relación con la respuesta del gasto cardíaco a una sobrecarga de fluidos y con la consiguiente mejoría en la hemodinámica, más que mediciones de presión de llenado del ventrículo derecho o izquierdo. Otras mediciones sensibles a la perfusión de los órganos, incluyendo la monitorización de la acidosis láctica y de la lactacidemia, deben también usarse para guiar la resucitación con fluidos. La precocidad del tratamiento y la rapidez con que se resuelven los signos de hipoperfusión tisular son aspectos fundamentales del manejo, puesto que están en íntima relación con el pronóstico

Septic shock is a state of tissue hypoperfusion in the context of a systemic inflammatory response syndrome, characterized clinically by excessive vasodilatation and the requirement of vasopressor agents in order to maintain the perfusion pressure of organs system. The typical hyperdynamic cardiovascular response is not present in all the patients, which means that its presence or absence should not be used for the diagnosis of septic shock. The treatment requires the normalization of volemia and the administration of inotropic agents in order to normalize the cardiac output if it is low, and to increase the perfusion pressure of tissues. The treatment should be guided by an adequate monitoring. The use of techniques that make possible to assess right ventricle preload is preferable, more than isolated measurements of ventricular filling pressures (that are not related to preload nor to the response of the patient to fluids overload). Recently, it has been shown that the variation of pulse pressure is related to the response of the cardiac output to fluid overload and to the consequent hemodynamic improvement, more than measurements of right or left ventricle filling pressures. Other measurements sensitive to the organs perfusion should be also used to guide resuscitation with fluids, including monitoring of lactic acidosis and lactacidemia. Speed of treatment and speed with which the sings of tissue hypoperfusion are resolved are fundamental components of management because are closely related to prognosis