NMBAs can ameliorate the management of ventilation [20], limiting decruitment, inspiratory effort, and expiratory alveolar collapse [9]. Some studies demonstrated improved oxygenation using NMBAs, possibly related to the effects on reducing the work of breathing [12,21]. In a randomized controlled trial on patients with ARDS receiving conventional therapy plus placebo or NMBAs, treatment with cysatracurium exerted anti-inflammatory effects by reducing the concentration of interleukins and tumor necrosis factor-alpha in serum and bronchoalveolar lavage [5].

Intra-abdominal hypertension (IAH), defined as an intra-abdominal pressure (IAP) above 12 mmHg, is one of the possible conditions in which the use of NMBAs can improve lung function. It is estimated that around 20% of patients present with IAH on admission to the ICU and almost 50% will develop IAH within the first week in the ICU [21,22]. IAH often progresses with an upper shift of the diaphragm and decreased lung volume and chest wall compliance, resulting in increased airway pressures [23] and decreased oxygenation [24]. Although abdominal contractions can falsely increase IAP values, to date, no recommendation on increasing sedation or using NMBAs to accurately measure IAP has been defined [24]. A recent guideline for the management of IAH and abdominal compartment syndrome in critically ill patients highlighted the possibility of considering the use of NMBAs for persistent IAH [25].

When paralyzing the patient, it is always important to consider the possibility of the development of complications associated with the administration of NMBAs, such as corneal abrasions [4] and venous thrombosis [26], and complications associated with prolonged immobilization such as ICUAW and myopathy. The relationship between ICUAW and NMBAs is controversial [4]. Although a recent meta-analysis did not show an association between NMBAs and neuromuscular dysfunction acquired in critical illness (odds ratio (OR), 1.21; 95% confidence interval (CI), 0.67–2.19), merged data from all the included studies suggested a modest association (OR, 1.25; 95% CI, 1.06–1.48; I = 16%) between NMBA use and ICUAW [27]. Many other studies have confirmed the association [28,29] or the potential risk [30] of the development of ICUAW with the use of NMBAs, but with a weak study design and high risk of bias because of the multi-factorial causes of ICUAW and heterogeneous outcomes [31]. In this uncertainty, the association between the use of NMBAs and critical weakness does not seem to be reasonable. Thus, recent SCCM guidelines did not relate the use of NMBAs with the risk of ICUAW, rather associating it with prolonged immobility and muscle disuse [32]. In addition, NMBAs impaired airway protective reflexes [33] and increased the risk of upper airway obstruction and pneumonia. Moreover, these patients needed deep sedation due to prolonged treatment with NMBAs [34].

Critically ill patients often have multi-organ-system disorders and receive treatments for longer periods; thus, the elimination of NMBAs and metabolites can be delayed, resulting in greater accumulation [4,35] and adverse events, difficulty in weaning from the ventilator [36], and the risk of venous thrombosis [26].

Patient–ventilator asynchrony is frequently observed during MV and is associated with worse outcomes and higher mortality [37].

Ventilatory under-assistance or over-assistance translates to different types of asynchronies [38]. Under-assistance could lead to an increased load on respiratory muscles, air hunger, and lung injury caused by excessive tidal volumes (V_T). Over-assistance could yield decreased inspiratory drive, which may result in reverse triggering, thus worsening lung injury. In addition, asynchronies may increase intrathoracic pressure, thus modifying cardiac output and hemodynamic status [39].

Yoshida et al. [40] demonstrated that an increase in distending pressure, caused by spontaneous effort in mechanically ventilated patients, could worsen a pre-existing lung injury through a pendelluft effect from non-dependent lung areas toward dependent areas because the diaphragm contraction is poorly transmitted across the pleural surface in an injured lung. Therefore, management of patient–ventilator asynchrony with neuromuscular blockade may be considered to minimize the lung and diaphragm injury associated with spontaneous breathing [41], especially in patients with ARDS [42].

The use of NMBAs in the critical care setting is frequently guided by personal experience and local practice, more than validated guidelines and recommendations [32]. NMBAs minimize the risk of ventilator-induced lung injury (VILI). However, the use of NMBAs requires adequate sedation to prevent VILI and may lead to extended time on MV, longer ICU stays, and increased risk of ventilator-associated pneumonia (VAP) [43,44]. NMBAs should be administrated with adequate sedation. Nevertheless, the sedation level is a factor that could affect the incidence of asynchrony. Observational studies showed an association between deep sedation and a higher incidence of patient–ventilator asynchronies [37,45].

A multi-center study showed a lower incidence of asynchronies with lighter sedation with dexmedetomidine compared with deeper sedation with propofol [46]. So, increasing sedation does not always represent an effective strategy to reduce asynchrony. When asynchrony is related to double triggering, deeper sedation associated with neuromuscular blockade could be taken into consideration. In contrast, in the case of reverse triggering, muscle effort could result in inflation so that a reduced sedation and NMBA strategy could be considered [47].