Introduction: Ventilator-induced Lung Injury: Not Only Air Leaks Ventilation-induced Pulmonary Edema and Related Findings: A Historical Perspective Ventilation-induced Pulmonary Edema: Hydrostatic or Permeability Edema? Experimental Evidence for Increased Vascular Transmural Pressure Evidence for Alterations in Alveolar–Capillary Permeability Contributions of the Static and Dynamic Lung Volume Components to Ventilator-induced Edema High-volume Lung Edema Low Lung Volume Injury Effects of High-volume Ventilation on Abnormal Lungs Effects of High-volume Ventilation on Injured Lungs Interaction between Severe Alveolar Flooding and Mechanical Ventilation Effects of Resting the Lung on Ventilator-induced Lung Injury Possible Mechanisms of Ventilation-induced Lung Injury Mechanisms of Increased Vascular Transmural Pressure Mechanisms of Altered Permeability Clinical Relevance

Ventilator-induced lung injury: lessons from experimental studies.

ContextStudies have shown that an inflammatory response may be elicited by
mechanical ventilation used for recruitment or derecruitment of collapsed
lung units or to overdistend alveolar regions, and that a lung-protective
strategy may reduce this response.ObjectiveTo test the hypothesis that mechanical ventilation induces a pulmonary
and systemic cytokine response that can be minimized by limiting recruitment
or derecruitment and overdistention.Design and SettingRandomized controlled trial in the intensive care units of 2 European
hospitals from November 1995 to February 1998, with a 28-day follow-up.PatientsForty-four patients (mean [SD] age, 50 [18] years) with acute respiratory
distress syndrome were enrolled, 7 of whom were withdrawn due to adverse events.InterventionsAfter admission, volume-pressure curves were measured and bronchoalveolar
lavage and blood samples were obtained. Patients were randomized to either
the control group (n=19): tidal volume to obtain normal values of arterial
carbon dioxide tension (35-40 mm Hg) and positive end-expiratory pressure
(PEEP) producing the greatest improvement in arterial oxygen saturation without
worsening hemodynamics; or the lung-protective strategy group (n=18): tidal
volume and PEEP based on the volume-pressure curve. Measurements were repeated
24 to 30 and 36 to 40 hours after randomization.Main Outcome MeasuresPulmonary and systemic concentrations of inflammatory mediators approximately
36 hours after randomization.ResultsPhysiological characteristics and cytokine concentrations were similar
in both groups at randomization. There were significant differences (mean
[SD]) between the control and lung-protective strategy groups in tidal volume
(11.1 [1.3] vs 7.6 [1.1] mL/kg), end-inspiratory plateau pressures (31.0 [4.5]
vs 24.6 [2.4] cm H2O), and PEEP (6.5 [1.7] vs 14.8 [2.7] cm H2O) (P<.001). Patients in the control group
had an increase in bronchoalveolar lavage concentrations of interleukin (IL)
1β, IL-6, and IL-1 receptor agonist and in both bronchoalveolar lavage
and plasma concentrations of tumor necrosis factor (TNF) α, IL-6, and
TNF-α receptors over 36 hours (P<.05 for
all). Patients in the lung-protective strategy group had a reduction in bronchoalveolar
lavage concentrations of polymorphonuclear cells, TNF-α, IL-1β,
soluble TNF-α receptor 55, and IL-8, and in plasma and bronchoalveolar
lavage concentrations of IL-6, soluble TNF-α receptor 75, and IL-1 receptor
antagonist (P<.05). The concentration of the inflammatory
mediators 36 hours after randomization was significantly lower in the lung-protective
strategy group than in the control group (P<.05).ConclusionsMechanical ventilation can induce a cytokine response that may be attenuated
by a strategy to minimize overdistention and recruitment/derecruitment of
the lung. Whether these physiological improvements are associated with improvements
in clinical end points should be determined in future studies.

https://jamanetwork.com/journals/jama/articlepdf/190583/jce80051.pdf

Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial.

Mechanical ventilation may cause injury to the ventilated lung. This article reviews the probable causes of such injury and ways to prevent it.

/pdf/ventilator-induced-lung-injury-18fdxcy8d6.pdf

Ventilator-Induced Lung Injury

Few problems facing the intensivist are as frustrating or as difficult to manage as multiple system organ failure (MSOF). While the precise etiology remains unknown, an integral feature is the development of a rampant systemic inflammatory response that persists unabated by host control mechanisms. Either a single massive insult, or a series of less intense insults (i.e., “two-hits”) appear to be necessary to overwhelm the individuals innate regulatory mechanisms. Often the lung is the first organ to fail, leading to initiation (or continuation) of ventilatory support. Although in some patients a precipitating nidus of infection or inflammation is identifiable, and lung injury is simply the first clinically evident manifestation of a systemic process, there remain a large number of patients in whom the explanation for progression from respiratory failure to multiple system organ failure is unclear. In this Perspective, we explore the hypothesis that mechanical ventilation may play a pivotal (and hereto unrecognized) role in the initiation and/or propagation of a systemic inflammatory response leading to MSOF in certain patients. We address this issue by examining the following questions: Can mechanical ventilation initiate or exacerbate lung injury/inflammation? Can lung injury/inflammation lead to systemic inflammation? Is there evidence of MSOF secondary to mechanical ventilation?

Multiple system organ failure. Is mechanical ventilation a contributing factor

Many animal studies have shown that high peak inspiratory pressures (PIP) during mechanical ventilation can induce acute lung injury with hyaline membranes. Since 1984 we have limited PIP in patients with ARDS by reducing tidal volume, allowing spontaneous breathing with SIMV and disregarding hypercapnia. Since 1987 50 patients with severe ARDS with a “lung injury score” ≥2.5 and a mean PaO2/FiO2 ratio of 94 were managed in this manner. The mean maximum PaCO2 was 62 mmHg, the highest being 129 mmHg. The hospital mortality was significantly lower than that predicted by Apache II (16% vs. 39.6%,x2=11.64,p 80, which has previously predicted 100% mortality from respiratory failure. Only 2 died, neither from respiratory failure. There was no significant difference in lung injury score, ventilator score, PaO2/FiO2 or maximum PaCO2 between survivors and non-survivors. We suggest that this ventilatory management may substantially reduce mortality in ARDS, particularly from respiratory failure.

/pdf/low-mortality-associated-with-low-volume-pressure-limited-3fs9duqfr1.pdf

Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome

Chez le lapin la ventilation a haute frequence ameliore les echanges gazeux. Les oscillations a haute frequence protegent le poumon des membranes hyalines contrairement a la ventilation traditionnelle

Comparison of conventional and high-frequency ventilation: oxygenation and lung pathology.

Comparison of Conventional and High-Frequency Ventilation: Oxygenation and Lung Pathology

The structure, distribution, and frequency of neuroendocrine (NE) cells in human fetal lung from early stages of development to term are described. Neuroendocrine cells were studied by electron microscopy and immunostaining for serotonin and bombesin, recently identified markers of these cells in human lung. The differentiation of NE cells within the airway epithelium proceeded centrifugally and followed the development of the bronchial tree. The first NE cells, identified at 8 weeks' gestation, appeared well-differentiated compared with adjacent epithelial cells, and were immunoreactive for serotonin. The first bombesin-immunoreactive cells were detected at 10 weeks' gestation. Fetal lungs from midgestation contained several ultrastructurally distinct NE cell types, distributed singly and in groups. Serotonin-immunoreactive cells were more frequent during early stages of development and were predominantly located in larger airways. Bombesin-immunoreactive cells became more numerous towards term and were concentrated in small peripheral airways. The well-differentiated appearance and large number of NE cells in fetal lung, and their increase in number towards term, suggest an important role for these cells during intrauterine life and neonatal adaptation. Whether this role involves neurohormonal regulation of fetal-neonatal pulmonary circulation or local (paracrine) or endocrine function requires further investigation.

J. E. Gillan

Papers

Comparison of conventional and high-frequency ventilation: oxygenation and lung pathology.

Comparison of Conventional and High-Frequency Ventilation: Oxygenation and Lung Pathology

Neuroendocrine cells in the developing human lung: morphologic and functional considerations.