3.1 Barotrauma and volotrauma

Since publication of the extended research of Dreyfuss et al. [22], the main mechanism of VILI was considered to be pressure-related and resulted in pneumothorax, pneumomediastinum or gas embolism [22, 23]. Subsequently, experimental data indicated that excessive lung strain caused by inappropriate tidal volumes (volotrauma) is the hallmark of pathophysiological mechanism of VILI [22, 23, 24]. Nowadays it is clear that both mechanisms are in close interaction, considering the fact that stress and strain are related through a proportionality constant represented by the tissue elastance of the lung [21, 23, 25]. In other words, the fundamental pathological mechanism of VILI is considered to be explained through the damage caused by pressure applied directly to the lung tissue (stress) connected to volume change beside the resting volume (strain) [26].

Since the early 2000 experimental evidence was confirmed by large clinical trials, such as the Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome—ARMA trial which proved that the use of low tidal volumes and avoidance of excessive lung stress are associated with an increased survival rate [27]. Another more recent trial (A Trial of intraoperative low-tidal-volume ventilation in abdominal surgery—IMPROVE trial) which included 400 patients also demonstrated a higher incidence of pulmonary and extrapulmonary complications in patients ventilated with higher tidal volumes [28].

Guivarch et al. [8] demonstrated in his experimental study on obese mechanical ventilated mice with tidal volumes calculated on actual body weight, that inflammation and interstitial oedema may occur after only two hours.

In the face of already proven deleterious effects of volotrauma and despite general recommendations regarding the use of proper tidal volumes according to ideal body weight (IBW), recent data suggest that obese patients are still at high risk for volotrauma occurrence [8]. A secondary analysis of the data resulted from the Intraoperative ventilation settings and their associations with postoperative pulmonary complications in obese patients—LAS VEGAS trial. The latter revealed that obese patients received ventilation with higher tidal volumes than predicted body weight [29]. Jaber et al. [30] also reported in his research which included almost 3000 patients that obese patients were ventilated with higher tidal volumes than patients with normal BMI.

3.2 Atelectrauma

Repeated alveolar recruitment and derecruitment is one of the most prominent factor contributing to atelectrauma [31]. The lack of lung homogeneity and the presence of regions with different elasticity amplify stress and strain [21, 32, 33]. As a result, increased shearing forces between aerated and atelectatic areas of the lung may occur, thereby causing atelectrauma [21, 34].

As previously mentioned, respiratory pathophysiological changes like airway narrowing and premature closure, typically identified in obese patients, expand the atelectatic areas promoting the lack of uniformity in the lung [14, 35]. Increased intraabdominal pressure, also present in obese patients, is further associated with lung collapse, atelectasis and increased transpulmonary pressure [36]. It was observed that collapsed lung areas affect neighbouring aerated areas causing deformation and increased stretch [37]. These structural changes eventually promote shear forces exacerbation [37]. So, beside the already existing atelectatic areas, mechanically ventilated patients with obesity are particularly prone to developing atelectrauma, especially in the absence of adequate ventilation parameters.

In order to prevent lung atelectasis and to minimize the risk of atelectrauma, researchers of the Effect of intraoperative high positive end-expiratory pressure (PEEP) with recruitment maneuvers vs. low PEEP on postoperative pulmonary complications in obese patients—PROBESE trial evaluated the effects of protective intraoperative ventilation using different levels of PEEP [38]. Despite expectations, no benefit was obtained in the group ventilated with increased PEEP [38]. Nestler et al. [39] demonstrated that an increased PEEP together with recruitment manoeuvres may be beneficial for intraoperative mechanical ventilation of obese patients, but these positive effects were not sustained during the postoperative period. Given these findings, Ball and Pelosi recommend using an increased fraction of inspired oxygen (FiO₂) over PEEP in order to prevent driving pressure increase and hyperinflation [40]. Moreover, these authors suggest that recruitment manoeuvres should only be used as a rescue method in severe hypoxemic dysfunctions [40].

3.3 Mechanical power or ”ergotrauma”

Beyond the already incriminated mechanical factors implicated in producing VILI, a recent concept has been advanced through which the mechanical power delivered during mechanical ventilation may be an independent factor for VILI development [41]. If until recently all the physical parameters implicated in mechanical ventilation (pressure, flow, resistance and frequency) were studied as individual data, it is assumed that the combined effects of these parameters should be considered [42]. Gattinoni et al. [42] proposed that mechanical power and its determinant factors may be appreciated through a complex equation derived from the equation of motion. Through this mathematical expression the authors could easily determine mechanical power as the result of the product between respiratory frequency and energy, the latter being the sum of the forces which open the lung, push the air into the lung and keep the lung open [25, 42, 43]. The importance of evaluating mechanical power may be useful in the pathogenic process of VILI because repeated tidal energy cycles above the lung tissue tolerance is associated with local structural disruption [43, 44]. Although this concept has recently aroused much interest, there is a lack of practical measurement tools for mechanical power in daily practice [41]. Nevertheless, Marini et al. [44] suggest a special consideration when it comes to setting a plateau pressure, or driving pressure and PEEP, underlining therefore that neither is reliable enough to measure the exact amount of energy delivered to the tissue with every cycle.

Considering the novelty of the concept and the lack of studies, both experimental and clinical, specifically targeting the evaluation of the impact of ergotrauma on mechanically ventilated obese patients, its effects are estimated based on the well-known patient-dependent factors.

According to Marini et al. [43] one conditional factor that may potentiate the deleterious effects of ergotrauma is represented by chest wall elasticity. Notwithstanding, this means that the energy transferred to the lung may be lower than anticipated due to the spent energy used to overcome the decreased chest wall compliance specific to obese patients [41]. In clinical practice this translates into an elevated threshold for the plateau pressure [41].

As stated above, lung homogeneity in obese patients is usually impaired due to the constitution of numerous atelectatic areas. As stated by the authors of the concept of ergotrauma, mechanical heterogeneity of the lung may predispose to raised regional transpulmonary pressures associated with alteration of dynamic micromechanics and increased shearing forces and stress [43].

Last but not least, it is underlined that a susceptibility of the patient to VILI, which is also the case of the obese patient, may also induce an elevated sensitivity to the harmful effects of mechanical power [43, 45]. Considering that there are no studies regarding the effects of mechanical power on the lungs of obese patients, Ball and Pelosi recommended using the same threshold as in non-obese patients, namely a mechanical power <20 J/min [40].

3.4 Biotrauma and the pre-conditioning mechanism

The effects of every injurious ventilator-related stimuli are considered to be biologically translated into an increased inflammatory mediator release and leucocyte recruitment [23, 34]. Beyond the local lung injuries, the systemic release of these inflammatory mediators may by associated with multiple organ failure and even death [37, 46].

The “biotrauma hypothesis” as part of VILI was initially outlined through the results obtained in experimental studies on subjects with ARDS ventilated in a protective manner. A lower level of proinflammatory mediators was also detected in the bronchoalveolar lavage after changing the ventilation strategy and increasing the tidal volume [23, 47]. However, the experimental data of Ricard et al. [47] concluded that solely large tidal volumes are not deleterious enough to induce ARDS and a previous lung damage may be mandatory.

The molecular mechanisms underlying biotrauma were mostly highlighted through experimental studies and are summarized in Table 1 [48, 49, 50].

The impact of biotrauma in obese patients lacks reliable studies. However, some assumptions may be made considering the data regarding obesity-related immune status.

On the one hand, obesity is associated with a chronic inflammatory state induced by augmented proinflammatory adipocytokines release, decreased anti-inflammatory cytokines and macrophage activation [52]. On the other hand, recent reports indicate that this continuous inflammatory state may offer some protection against further lung injuries, calling this effect as “pre-conditioning cloud” [53]. The concept of preconditioning evolved from the pharmacological process called hormesis and was recently applied in many medical fields including ischemic preconditioning [54]. The “pre-conditioning cloud” in obese patients proposed by Fernandez-Bustamante et al. [7] has evolved from the obesity-paradox according to which critically ill obese patients have a decreased rate of mortality [2, 3, 4, 53]. Considering that all these hypotheses are based on observations, further research studies are required.