Variable ventilation enhances ventilation without exacerbating injury in preterm lambs with respiratory distress syndrome

Abstract

Background: as compared with constant respiratory rate (RR) and tidal volume (V T ) during controlled conventional mechanical ventilation (cV), variable ventilation (VV) using the same breath-to-breath minute volume but variable V T and RRs enhances ventilation efficiency in preterm lambs. We hypothesized that if V T was adjusted to target permissive hypercarbia, VV would result in more efficient gas exchange without increasing inflammatory and injurious responses in the lung. Methods: Preterm lambs at 129 d gestation were anesthetized, tracheotomized, and randomized to either cV (n = 8) or VV (n = 8) using the same initial average V T and RR. Lung mechanics and gas exchange were measured intermittently, and average V T was adjusted to target partial pressure of arterial carbon dioxide (PacO 2 ) of 40-50 mm hg for 3 h. Lung injury and inflammation were assessed from bronchoalveolar lavage fluid, lung tissue, and peripheral blood. results: VV achieved permissive hypercarbia using a lower average V T , peak inspiratory pressure, and elastance (increased compliance) as compared with cV. Oxygenation and markers of lung tissue inflammation or injury were not different apart from a lower wet:dry tissue ratio in the VV lungs. conclusions: VV improves ventilation efficiency and in vivo lung compliance in the ovine preterm lung without increasing lung inflammation or lung injury. Variability is an inherent property of many biological systems. Variable breathing is especially evident in newborn infants (1), particularly those born premature for whom sigh breaths with tidal volume (V T ) more than twice the average breath volume are critical to the maintenance of resting lung volume (2). Current ventilatory strategies advocated for the preterm infant focus on tightly regulating the size of each breath using volume guarantee or volume targeting of ventilator assisted/controlled breaths. An alternative approach, variable ventilation (VV), maintains a constant breath-to-breath minute volume throughout the study but distributes delivered V T and respiratory rate (RR) such that the lung may receive V T less than or greater than the average V T . In adult animal models, VV improves oxygenation and enhances gas exchange as compared with controlled conventional mechanical ventilation (CV) (3)(4)(5). Recently, we showed that VV enhanced both respiratory mechanics and gas exchange in preterm lambs as compared with CV that tightly regulated both breath size and rate (6), similar to findings of studies in adult animal models. However, unlike the adult animal studies, VV did not improve oxygenation in the preterm lambs, most likely due to shunting across fetal channels.Given previous evidence that serial repeated large V T at the initiation of ventilation in the preterm lung increases markers of inflammation and injury suggestive of volutrauma (7,8), successful clinical translation of VV in the preterm infant requires evidence that intermittent distributed sigh breaths are not injurious to the immature lung. Although there was no evide...

Variable ventilation improves pulmonary function and reduces lung damage without increasing bacterial translocation in a rat model of experimental pneumonia

“…In addition, different aspects of the pneumonia model, including functional, structural, and ultrastructural features, the inflammatory response, and the potential for translocation of bacteria during mechanical ventilation, were characterized in detail (Additional file 1: Figure S1, Tables S1, S2, and S3). We chose a CV of 30% in V T because this level of variability has been shown to improve lung function [8, 23] and reduce lung damage in direct ARDS in rats [8], as well as other species [9, 24–27]. Additionally, controls with i.t.…”

“…The use of variable tidal volumes, i.e., variable ventilation, has been shown to improve pulmonary function and reduce lung damage in different experimental models of direct [7–9] and indirect [8, 10] ARDS. Nevertheless, variable ventilation has not been tested during pneumonia.…”

Variable mechanical ventilation

“…Of these, 1,778 were excluded after reading the title and abstract because they did not address the central theme of the study. There were discrepancies in the number of articles (28, 30 (9,10) and 31 (9-11) ) selected by the three examiners. Five other articles were extracted from the references of the articles identified in the electronic search.…”

“…(21) In three studies, including an experimental ARDS model induced by oleic acid (26) and a preterm lamb model, (10,27) the variable controlled MV did not improve arterial oxygenation compared with conventional controlled MV. The improvement in gas exchange was also evidenced during variable PSV compared with conventional PSV in ARDS models.…”

Trends in mechanical ventilation: are we ventilating our patients in the best possible way?

“…Moreover, variability in the respiratory system has been found to be important for cell activity, as it positively modulates surfactant secretion [44, 45]; it is also related to the maturation of breathing control in infants [46, 47] and correlates with weaning success [48–50]. Animal studies have shown that variability improves ventilation efficiency and lung compliance in the preterm lung without increasing lung inflammation or lung injury [51, 52]. …”