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distress syndrome were enrolled, 7 of whom were withdrawn due to adverse events.InterventionsAfter admission, volume-pressure curves were measured and bronchoalveolar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.

The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system.

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

Immediate and early trauma deaths are determined by primary brain injuries, or significant blood loss (haemorrhagic shock), while late mortality is caused by secondary brain injuries and host defence failure. First hits (hypoxia, hypotension, organ and soft tissue injuries, fractures), as well as second hits (e.g. ischaemia/reperfusion injuries, compartment syndromes, operative interventions, infections), induce a host defence response. This is characterized by local and systemic release of pro-inflammatory cytokines, arachidonic acid metabolites, proteins of the contact phase and coagulation systems, complement factors and acute phase proteins, as well as hormonal mediators: it is defined as systemic inflammatory response syndrome (SIRS), according to clinical parameters. However, in parallel, anti-inflammatory mediators are produced (compensatory anti-inflammatory response syndrome (CARS). An imbalance of these dual immune responses seems to be responsible for organ dysfunction and increased susceptibility to infections. Endothelial cell damage, accumulation of leukocytes, disseminated intravascular coagulation (DIC) and microcirculatory disturbances lead finally to apoptosis and necrosis of parenchymal cells, with the development of multiple organ dysfunction syndrome (MODS), or multiple organ failure (MOF). Whereas most clinical trials with anti-inflammatory, anti-coagulant, or antioxidant strategies failed, the implementation of pre- and in-hospital trauma protocols and the principle of damage control procedures have reduced post-traumatic complications. However, the development of immunomonitoring will help in the selection of patients at risk of post-traumatic complications and, thereby, the choice of the most appropriate treatment protocols for severely injured patients.

A. J. Pollok

Papers

Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups