Mechanical Ventilation for Paediatric ARDS

Mechanical ventilation (MV) is clearly of benefit for children with ARDS although there are many questions that require study (Fig. 19.2) [81]. Both controlled and assisted modes of ventilation are used by paediatric critical care practitioners, irrespective of the size of the breath (pressure versus volume). However, superiority of one mode over the other has not been demonstrated [122]. This also applies to the

Fig. 19.2 Graphic summary of issues in the ventilatory management of paediatric acute respiratory distress syndrome (PARDS) (Reprinted with permission from Kneyber et al. [81]) use of ventilator modes that allow the patient to trigger the machine breath. Adult data has suggested that patient-ventilator asynchrony (i.e. no synchronisation between patient’s demand and the delivered breaths) is associated with increased morbidity, but paediatric data is lacking [40]. Neurally adjusted ventilatory assist (NAVA) uses the electrical activity signal of the diaphragm to trigger inspiration. So far, paediatric experience with this alternative mode of triggering is limited. Piastra and colleagues showed that infants recovering from severe ARDS had a shorter duration of respiratory support when they were weaned with NAVA compared with pressure support ventilation [118].

MV may also exacerbate or even initiate lung injury and has therefore been identified as a predictor for poor outcome [131]. The development of this so-called ventilator- induced lung injury (VILI) has led to the concept of lung-protective ventilation (LPV). In brief, LPV encompasses the delivery of small tidal volume (Vt) to avoid end-inspiratory overdistension (i.e. volutrauma) and the application of a certain level of positive end-expiratory pressure (PEEP) to prevent repetitive opening and closure of alveoli (atelectrauma). The issue of LPV in PARDS is the subject of scientific debate. A large randomised controlled trial (RCT) in adult patients with ARDS according to the NAECC criteria showed improved patient outcome with 6 mL/kg ideal body weight (IBW) compared with 12 mL/kg/IBW [108]. However, other adult studies could not demonstrate a positive effect on mortality when 7 mL/kg IBW was compared with 10 mL/kg IBW [117]. Subsequent meta-analyses concluded that a Vt < 10 mL/kg per predicted body weight was associated with higher survival [21, 22]. To date, a paediatric counterpart of the ARDS Network trial has not been performed. Remarkably however is the data coming from observational studies, showing an inverse or no relationship between Vt and mortality in children [46, 76](20) (Table 19.3). A systematic review of the available paediatric data could also not identify a specific threshold when Vt could be considered safe, irrespective of the presence of ARDS [39]. Experimental work has shown that very young animals were less susceptible to VILI compared with adult animals when subjected to injurious ventilation with supra-physiologic Vt (i.e. 30-40 mL/kg body weight) [84]. All of this challenges the role of volutrauma in PARDS. Various explanations may be proposed, including the incorrect measurement of Vt. The ventilator overestimates the Vt delivered to the patient in young children, signifying the need for correct measurement near the Y-piece of the patient circuit in children below 10-15 kg [25]. In addition, in adults, the Vt is calculated by predicted body weight for age, height and gender. In paediatric practice Vt is usually calculated by actual body weight. A paediatric counterpart of the ARDS Network trial is eagerly awaited, although such a trial seems very unlikely for various reasons including the need for a large sample size (i.e. > 500 patients) [82]. Interestingly, paediatric critical care practitioners may have already found the solution in targeting the optimal Vt in PARDS. Unlike in adult critical care, there is a large tendency to use pressure- controlled (PC) ventilation instead of volume-controlled (VC) ventilation. In contrast with the paediatric data showing an inverse relationship between tidal volume and mortality, these same studies did confirm an association between inspiratory pressures and mortality (Table 19.3). This is in line with the assumption that the patient with a more severe lung injury characterised by small residual inflatable lung volume

Table 19.3 Summary of studies reporting on ventilation practices and outcomes in paediatric acute respiratory distress syndrome (PARDS)

(continued)

Table 19.3 (continued)

¹ Mean ± standard deviation. ²median (25-75 interquartile range). ALI acute lung injury, AHRF acute hypoxaemic respiratory failure, у year, OR odds ratio, Vt tidal volume available for alveolar ventilation and therefore gas exchange (which is also known as the baby lung concept) should receive tidal volumes below physiologic values [56]. Patient subgroup analysis from the ARDS Network trial showed that only patients with poor respiratory system compliance at study entry had a benefit in terms of survival when randomised to the 6 mL/kg study arm [41]. This observation suggests strongly that physicians tend to use lower Vt resulting in higher inspiratory airway pressures in the sicker patients (i.e. patients with lower respiratory system compliance) at the onset of ARDS and mechanical ventilation. This latter observation is in alignment with the data from the other paediatric observational study showing that patients with higher initial lung injury scores were ventilated by smaller tidal volumes and showed worse outcome [76]. This goes along with the concept of keeping lung tissue strain (the ratio between inflated volume and functional residual capacity) low in order to protect the lung [94]. Reanalysis of adult data also showed the importance of limiting the driving pressure (i.e. the ratio of Vt of compliance at a zero-flow state) in ARDS [30]. However, given the absence of paediatric data, no recommendation can be made on the upper limit of the plateau pressure that is allowable. The same applies to the level of PEEP. Levels of PEEP should be set to prevent lung unit collapse at expiration and to avoid tidal recruitment at each breath cycle (collapse-opening-recollapse injury). Although adult data indicated that higher levels of PEEP may be associated with lower mortality, such issues remain to be resolved in paediatrics. Remarkably, paediatric physicians tend to tolerate a higher level of FiO₂ instead of turning up the PEEP because they worry about haemodynamic consequences.

From a theoretical perspective, high-frequency oscillatory ventilation (HFOV) is an ideal LPV mode [83]. With HFOV, a continuous distending pressure (CDP) is generated maintaining lung volume, with superimposed small oscillations in a frequency range of 5-15 Hz allowing for gas exchange. Paediatric critical care practitioners cherish HFOV despite the lack of scientific evidence. To date, there has been only one randomised controlled trial comparing high-frequency oscillatory ventilation to conventional mechanical ventilation in 70 children with diffuse alveolar disease and/or air leak syndrome [8]. This study showed that HFOV utilising an aggressive volume recruitment strategy resulted in a significant improvement in oxygenation and a decreased requirement for supplemental oxygen at 30 days. However, 30-day mortality was not changed in this particular trial. A meta-analysis of all six paediatric and adult clinical trials demonstrated improved mortality in patients randomised to HFOV [133]. However, two large randomised studies in adults with moderate-to-severe (early) ARDS troubled the discussion on HFOV in PARDS [49, 155]. Whereas in the OSCillation for ARDS (OSCAR) trial no difference in 30-day mortality was observed, and the OSCILLation for ARDS Treated Early (OSCILLATE) trial was prematurely stopped (after the 500 patient analyses) by the steering committee because of a significantly higher in-hospital (47% vs 35%) and 60-day mortality (47% vs 38%) in the HFOV group. In the absence of paediatric trials, a post hoc analysis of data of paediatric patients enrolled in a pro- tocolised sedation trial showed similar mortality rates but prolonged duration of MV among patients managed with HFOV, calling for a paediatric RCT to examine the role of HFOV in PARDS [12].

Weaning from the ventilator should start as early as possible, although no paediatric data is available identifying a specific threshold when to start and how to do the weaning itself. Also, at present no paediatric criteria have been validated to discriminate extuba- tion success and failure as well as commonly used adult parameters to monitor weaning including the rapid shallow breathing index (RSBI) [109]. The same applies to the application of spontaneous breathing trials (SBT) and extubation readiness test (ERT). It is unclear what the optimal SBT in PARDS is (i.e. using either continuous positive airway pressure (CPAP), a low level of pressure support ventilation or T-piece ventilation).

Non-invasive positive pressure ventilation (NPPV) is increasingly being used to treat respiratory failure from a variety of aetiologies in children, including paediatric ARDS [124]. Despite this growing, there is much uncertainty about the indications, strategies and effects on patient outcome for the use of NPPV, especially in paediatric ARDS [47, 128]. There are several paediatric prospective and retrospective cohort studies describing the use of NPPV for acute respiratory failure, but most include a heterogeneous population that includes mild-to-severe ARDS. Thus, it remains the subject of debate if NPPV actually prevents the need for endotracheal intubation. Observational studies indicated that the median intubation rate for children with severe PARDS is 57% [47]. In only one randomised controlled trial of 50 children with acute hypoxaemia respiratory failure, the intubation rate was significantly lower (28% vs 60%, p = 0.045) when NPPV was compared with standard care. However, this particular study included also patients with mild PARDS.

Extracorporeal Life Support

Extracorporeal life support (ECLS) is a modified form of cardiopulmonary bypass. During ECLS, blood is pumped through an extracorporeal circuit containing a membrane oxygenator in which O2 is added and CO2 removed from blood, which is then returned to the patient. An increasing number of paediatric patients with respiratory failure are managed with veno-venous or veno-arterial ECLS despite the absence of a great deal of data showing improved patient outcome [36]. No randomised trials have been performed in PARDS, making it difficult to determine the efficacy of ECLS. In one retrospective study, it was found that the use of ECLS was associated with a reduced mortality in paediatric acute respiratory failure [63]. Thus, ECLS should be considered in severe PARDS where the cause of the respiratory failure is believed to be reversible [36].