High tidal volume ventilation does not exacerbate acid-induced lung injury in infant rats

Sly, Peter D.; Nicholls, P.K.; Berry, Luke J.; Hantos, Zoltán; Cannizzaro, Vincenzo

doi:10.1016/j.resp.2013.07.013

Cited by 13 publications

(8 citation statements)

References 37 publications

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“…Moreover, alterations in surfactant PL profile are associated with alveolar instability and impaired lung function. In fact, ARDS patients and ALI animal models showed decreased PC with concomitantly increased SM and lyso-PC levels in BALF (12,18,19,24,39). In our study, both SM and lyso-PC content was significantly higher after V T 24PEEP1 ventilation when compared to all other groups.…”

Section: Discussionsupporting

confidence: 45%

Impact of high tidal volume ventilation on surfactant metabolism and lung injury in infant rats

Wiegert

Greco

Baumann

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

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The poorly understood tolerance towards high tidal volume (VT) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high VT with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion leading to improved lung function and whether extreme mechanical ventilation affects intracellular lamellar body formation and exocytosis. Fourteen days old rats were allocated to five groups: non-ventilated controls, PEEP 5 cmH2O with VT of 8, 16, and 24 mL/kg, respectively, and PEEP 1 cmH2O with VT 24 mL/kg. Following 6 hours of ventilation, lung function, surfactant proteins and phospholipids, and lamellar bodies were assessed by forced oscillation technique, quantitative real-time polymerase chain reaction, mass spectrometry, immunohistochemistry, and transmission electron microscopy, respectively. High VT (24 mL/kg) with PEEP of 5 cmH2O improved respiratory system mechanics and was not associated with lung injury, elevated surfactant protein expression, or surfactant phospholipid content. Extreme ventilation with VT 24 mL/kg and PEEP 1 cmH2O produced a mild inflammatory response and correlated with higher surfactant phospholipid concentrations in bronchoalveolar lavage fluid without affecting lamellar body count and morphology. Elevated phospholipid concentrations in the potentially most injurious strategy (VT 24 mL/kg, PEEP 1 cmH2O) need further evaluation and might reflect accumulation of biophysically inactive small aggregates. In conclusion, our data confirm the resilience of infant rats towards high VT-induced lung injury and challenge the relevance of surfactant synthesis, storage, and secretion as protective factors.

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Section: Discussionsupporting

confidence: 45%

Impact of high tidal volume ventilation on surfactant metabolism and lung injury in infant rats

Wiegert

Greco

Baumann

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

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“…However, many of the experimental studies have used supraphysiologic Vt to study the effects on lung injury, making it difficult to extrapolate the observed differences between pediatric subjects and adults into clinical practice. However, one group of investigators has shown that a Vt in the physiological range exacerbated pre-existing lung injury (80). We therefore propose that VILI is a definite entity in the pediatric population, but that it's propensity increases with increasing age following a yet-unknown function, and reaches susceptibility similar to adults at a yet-unknown age.…”

Section: Clinical Implications and Directions For Future Researchmentioning

confidence: 86%

Ventilator-induced Lung Injury. Similarity and Differences between Children and Adults

Kneyber

Zhang

Slutsky

2014

Am J Respir Crit Care Med

115

125

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It is well established that mechanical ventilation can injure the lung, producing an entity known as ventilator-induced lung injury (VILI). There are various forms of VILI, including volutrauma (i.e., injury caused by overdistending the lung), atelectrauma (injury due to repeated opening/closing of lung units), and biotrauma (release of mediators that can induce lung injury or aggravate pre-existing injury, potentially leading to multiple organ failure). Experimental data in the pediatric context are in accord with the importance of VILI, and appear to show age-related susceptibility to VILI, although a conclusive link between use of large Vts and mortality has not been demonstrated in this population. The relevance of VILI in the pediatric intensive care unit population is thus unclear. Given the physiological and biological differences in the respiratory systems of infants, children, and adults, it is difficult to directly extrapolate clinical practice from adults to children. This Critical Care Perspective analyzes the relevance of VILI to the pediatric population, and addresses why pediatric patients might be less susceptible than adults to VILI.

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“…Similar findings were made in mice in a double-hit model in juvenile (21 days) and adult (16 weeks old) C57BL/6 mice treated with aerosolised lipopolysaccharide and ventilated for 3 hours with Vt 15 mL/kg (11). Of note, all experimental studies used supraphysiologic Vt, which challenges translating the results into clinical perspective although one study showed an exacerbation of acid-induced lung injury also occurring when physiological Vt was delivered (12). Furthermore, the findings of these studies may have been influenced by the fact that the injurious stimulus might be lower in the infant rat when Vt was dictated by bodyweight rather than by body size.…”

Section: Vili In Children: Data From Animal Studiesmentioning

confidence: 57%

Ventilator-induced lung injury in children: a reality?

Koopman¹,

Jager²,

Blokpoel³

et al. 2019

Ann. Transl. Med.

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Mechanical ventilation (MV) is inextricably linked to the care of critically ill patients admitted to the paediatric intensive care unit (PICU). Even today, little evidence supports best MV practices for life-threatening acute respiratory failure in children. However, careful attention must be paid because this life-saving technique induces pulmonary inflammation that aggravates pre-existing lung injury, a concept that is known as ventilator-induced lung injury (VILI). The delivery of too large tidal volumes (Vt) (i.e., volutrauma) and repetitive opening and closure of alveoli (i.e., atelectrauma) are two key mechanisms underlying VILI. Despite the knowledge of these mechanisms, the clinical relevance of VILI in critically ill children is poorly understood as almost all of our knowledge has been obtained from studies in adults or experimental studies mimicking the adult critical care situation. This leaves the question if VILI is relevant in the paediatric context. In fact, limited paediatric experimental data showed that the use of large, supraphysiologic Vt resulted in less inflammation and injury in paediatric animal models compared to adult models. Furthermore, the association between large Vt and adverse outcome has not been confirmed and the issue of setting positive end-expiratory pressure (PEEP) to prevent atelectrauma has hardly been studied in paediatric clinical studies. Hence, even today, the question whether or not there VILI is relevant in pediatric critical remains to be answered. Consequently, how MV is used remains thus based on institutional preferences, personal beliefs and clinical data extrapolated from adults. This signifies the need for clinical and experimental studies in order to better understand the use and effects of MV in paediatric patients with or without lung injury.

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High tidal volume ventilation does not exacerbate acid-induced lung injury in infant rats

Cited by 13 publications

References 37 publications

Impact of high tidal volume ventilation on surfactant metabolism and lung injury in infant rats

Impact of high tidal volume ventilation on surfactant metabolism and lung injury in infant rats

Ventilator-induced Lung Injury. Similarity and Differences between Children and Adults

Ventilator-induced lung injury in children: a reality?

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