Positive end-expiratory pressure improves elastic working pressure in anesthetized children

There are many detrimental effects of positive pressure mechanical ventilation (MV) to the lung parenchyma, giving shape to the entity we know as ventilator induced lung injury (VILI) [1, 2]. Despite that it was initially described for injured lungs [3], VILI has been recognized to affect patients with uninjured lungs, triggering many pathways of local and systemic inflammation [1‐4]. Positive pressure MV can cause VILI even when applied for short periods of time, and the role of protective MV during anesthesia has become important for preventing postoperative complications [5‐10]. Although the exact incidence of VILI during general anesthesia is unknown, the lungs of patients under general anesthesia are especially vulnerable to VILI, since anesthetic induction reduces the end expiratory lung volume (EELV) by 9–25% in adults and up to 46% in children [11‐15]. Cyclic opening and collapsing of alveoli have been indicated as one of the primary mechanisms of VILI during anesthesia. Imaging studies have shown that general anesthesia induces atelectasis of dependent regions and that the use of PEEP prevents its formation [3, 5, 9, 10, 14]. Protective ventilation during general anesthesia [16, 17] to limit tidal volume (6–8 ml/kg) has been widely accepted and incorporated into the operating room (OR), but PEEP use is still not a common practice for patients undergoing general anesthesia [6‐10, 17, 18].

In the absence of respiratory muscle activity, working pressure of the respiratory system is the pressure needed to overcome frictional forces, elastic forces and impedance. In this way, an improvement in CRS reflects lower elastic work pressures and, therefore, a pending situation of its more favorable dynamic pressure/volume curve (P/V curve) [19]. These observations also have been described in pediatric animal models [20, 21].

There is little evidence to guide MV during general anesthesia in children [18, 22, 23]. MV parameters are primarily dependent on anesthesiologist preferences and on the characteristics of anesthesia machines [24]. Facing this scenario, many scientific societies have pointed as priority areas of research to the pathophysiology, respiratory mechanics and practice of MV in children for improving outcomes and reducing secondary long-term lung injury [23].

With these facts in mind, we sought to compare respiratory mechanics of setting PEEP at 5 cmH₂O compared to ZEEP (PEEP set at 0 cmH₂O) in anesthetized children without acute pulmonary pathology undergoing elective surgery. We hypothesized that usual respiratory mechanics parameters, measured with a commercial mechanical ventilator, would identify a more protective ventilation with addition of PEEP 5 cmH₂O. Special emphasis was placed on evaluation on respiratory work pressure, flow patterns, resistance and inspiratory and expiratory time constants.

Thirty patients were included in the study. Sixty percent were male, the median age was 39 months (15–61.3), and weight was 15 kg (10.6–21).

Sixty percent of patients received inhaled anesthesia and 40% mixed inhalation and intravenous anesthesia. Abdominal surgery was the most frequent (20 cases), mostly hernioplasty. Malformation of the digestive tract was the most frequent comorbidity, present in 7 patients. Table 1 shows clinical characteristics of included patients.

There were no complications related to the protocol. Table 2 shows ventilatory parameters and respiratory system mechanics for the study population with ZEEP and PEEP of 5 cmH₂O. After setting PEEP at 5 cmH₂O we observed an increase in PIP, P_PL and Paw, with a concomitant decrease in iPEEP and ∆P. Figure 1 shows individual changes on ∆P throughout the study. No modifications were done on V_T, and thus, changes on ∆P were coupled to variation on C_RS.

There was a moderate correlation between age and ideal body weight and changes in Q_E and changes in K_TE. Additional file 3 shows the correlation between changes in respiratory parameters and age and ideal body weight. No other correlations with age and weight were found.

In this study, we measured pulmonary mechanics in anesthetized healthy children on MV for elective surgery at ZEEP and PEEP 5 cmH₂O using a commercially available mechanical ventilator. Setting PEEP at 5 cmH₂O resulted in a significant decrease in ∆P and iPEEP, thereby improving C_RS. Changes observed in respiratory mechanics after setting PEEP at 5 cmH₂O are summarized in Fig. 2.

We also found a decrease in Q_E when PEEP was applied. All these findings are indirect signs of lungs in a better position in dynamic P/V curve, suggesting that the addition of a low level of PEEP improves respiratory mechanics.

The effect of PEEP on patients with ARDS was described more than a decade ago, promoting recruitment of non-aerated lung volume and increasing EELV. More recently, many investigators have shown that PEEP should be incorporated to lung protective strategy during the perioperative period in patients at risk for ARDS as well as previously healthy patients [6, 8‐10]. In this setting, hypoxemia was not associated with the reduction in EELV, and thus, hypoxemia is thought to be a poor predictor of potential injurious MV. Similar findings have been described in children. Serafini et al. described densities in dependent regions of both lungs on CT scan of 10 infants after induction of anesthesia. They observed reopening of the collapsed lung with addition of 5 cmH₂O of PEEP for 5 min [14]. Kadini et al., in a small study of 8 anesthetized children (range between 2.5 and 6.5 years old), described that 5 cmH₂O resulted in a significant increase of VT; thus, C_RS improved [24].

Our results show that the addition of PEEP sets the respiratory system in a better position of the P/V curve, probably related to the reduction of the atelectasis in lung dependent zones after induction of anesthesia and MV with ZEEP. An increase in EELV, maintaining the same V_T, denotes a reduction in global strain and, potentially, VILI [26].

∆P has taken high priority after the recent pooled data analysis of adult patients with ARDS that showed a significant relationship with mortality [27]. ∆P represents the pressure required for the movement of inspiratory flow and depends on the lung and chest wall viscoelastic resistance [28]. Recently, Neto et al. in a meta-analysis of 2250 patients under general anesthesia found that high ∆P was the only MV parameter associated with postoperative complications [29]. Even more, they found that changes in PEEP that resulted in an increase in ∆P were associated with more postoperative pulmonary complications. It is not surprising that in these studies, ∆P was the best predictor of unfavorable outcomes. We believe that the best performance of this parameter is because it integrates the set tidal volume and the patient’s compliance, thus giving a more precise idea of the individual conditions of each patient.

In our patients, we observed a 14.8% (CI95% 9.3,20.3%) reduction of ∆P when PEEP of 5 cmH₂O was applied. The range of improvement was very wide and only one patient had a significant increase in ∆P (greater than 10%). These results are in accordance with a study by Wirth et al. They elegantly showed, with electric impedance tomography in 30 anesthetized children, that changing PEEP from 2 cmH₂O to 5 cmH₂O homogenizes regional lung ventilation [30]. One of our patients had a significant increase of ∆P. This a very good example that ventilatory settings need to be tailored individually, because adding 5 cmH₂0 of PEEP probably led to overdistension in this patient. We maintained the set V_T after applying PEEP of 5 cmH₂O; thus, the reduction of ∆P was dependent on the improvement in C_RS. The improvement in C_RS and EELV may be seen as minor, but we believe that even these small changes may have significant consequences during and after surgery, reducing lung inflammation, alteration of gas exchange, among others. Experimental and clinical data have shown that injurious ventilatory parameters can generate detrimental effects, even when applied for short periods of time [1, 2, 31, 32].

The prolongation of K_TI and K_TE with PEEP of 5 cmH₂O probably reflects mathematical coupling of changes on C_RS without modifications on airway resistance. In the same way, the observed lower expiratory flow is related to the lower ∆P. These parameters are indirect markers of improvement on respiratory system mechanics and more protective ventilation.

Our study has some limitations. Respiratory mechanics measurements were done before the surgery, after a short period of applied PEEP; thus, we cannot extrapolate these findings to other surgical timings, e.g., during pneumoperitoneum, when the effect of PEEP preventing lung collapse could be even higher. Due to small size of patients, we did not measure pleural pressure, so we could not determine the contribution of the chest wall to C_RS. Included patients were heterogeneous and age range is wide, so in the absence of normal reference data, we cannot generalize these results to all pediatric patients (i.e., younger patients have higher chest compliance, being at higher risk for derecruitment of the lung on ZEEP). Finally, we have to acknowledge that setting of MV parameters can directly modify the component of the equation of motion (i.e., Q_I, RR, I:E ratio), but we tried to standardize the ventilatory setting during measurements. Despite these limitations, we consider our observation of the effect of PEEP in anesthetized children under mechanical ventilation important in terms of a pathophysiological approach to reduce VILI.

Setting PEEP at 5 cmH₂O in children during general anesthesia improved elastic working pressure of the respiratory system, decreasing driving pressure and intrinsic PEEP. These findings are indirect signs of lungs in a better position in pressure/volume curve, suggesting that the addition of a low level of PEEP improves respiratory mechanics. These findings may be measured with usual mechanical ventilators and anesthesia machines, analyzing respiratory system mechanics after an inspiratory and expiratory hold. Future studies in infants are needed to address respiratory mechanics during anesthesia, ideally in a specific age group and pathologies with high-risk postoperative complications. A better understanding of respiratory system mechanics in children during general anesthesia may lead to a better titration of mechanical ventilation, preventing VILI.