Dependency of respiratory system mechanics on positive end‐expiratory pressure and recruitment maneuvers in lung healthy pediatric patients—A randomized crossover study

The lungs of pediatric patients are subjected to tidal derecruitment during mechanical ventilation and in contrast to adult patients this unfavorable condition cannot be resolved with small c increases. This raises the question if higher end‐expiratory pressure increases or recruitment maneuvers may resolve tidal derecruitment in pediatric patients.


| INTRODUC TI ON
Positive end-expiratory pressure (PEEP) is supposed to counteract tidal lung derecruitment during mechanical ventilation. 1 However, in pediatric patients PEEP is usually set lower compared with adults and high closing capacity promotes intraoperative atelectasis and tidal derecruitment in pediatric patients. In an earlier study, lungs of mechanically ventilated pediatric patients showed signs of tidal derecruitment at PEEP 2 cmH 2 O which was not dissolved when PEEP was increased to 5 cmH 2 O. 2 Therefore, we aimed to investigate if a higher PEEP of 7 cmH 2 O and recruitment maneuvers would be adequate measures for preventing tidal derecruitment during mechanical ventilation of pediatric patients. For this purpose, we ventilated pediatric patients subsequently at PEEP 3 or 7 cmH 2 O or vice versa and without and with recruitment maneuvers between the PEEP changes, respectively, and evaluated global respiratory system mechanics from recordings of respiratory data and regional ventilation from electrical impedance tomography (EIT).

| MATERIAL S AND ME THODS
The study protocol was approved by the ethics committee of the University of Freiburg (EK03/15) and registered at the German Offline data analyses were performed using Matlab. The dynamic compliance of the respiratory system (C RS ) at the different PEEP levels was calculated for every patient via multilinear regression analysis. Using the gliding-SLICE method, the volume-dependent compliance curves were calculated from which the respective compliance profile was determined as described earlier. 3 In brief, the intratidal pressure-volume curve was subdivided into 21 equidistant volume segments. The segment-specific compliance was then calculated from the data surrounding each segment (SLICE) within the Functional EIT images were generated by averaging the pixel-wise differences between raw images corresponding to start and end of expiration for each recorded sequence in each patient.
From these functional images, regional tidal variation was determined as a measure for ventilation distribution in the ventral (TV v ) region. 5 In brief, the functional impedance images were first split into ventral and dorsal parts. 6 Subsequently, impedance values were summed up separately in these regions of interest (x i,v and x i,d ) and related to the sum of impedances (x i ) of the whole functional EIT image: Additionally, regional ventilation gain and loss 7 were calculated for each group by subtracting the functional EIT images from the second PEEP phase from those of the first PEEP phase and splitting them into ventral and dorsal regions. In order to achieve meaningful results, the lung area of each patient was determined using the lung area estimation method 6 for this purpose. Subsequently, this area was applied to all functional impedance images. Furthermore, a threshold of 10% for relevant gain and loss pixels was used and applied similar to the lung area estimation. In brief, the highest gain or loss value was determined and only pixels with more than 10% of this value were included into the gain and loss calculation. This mitigates the drawback of gain and loss calculation to some extent, since in its original form very small fluctuations with no relevant information in ventilation would result in a gain or loss. Scalable data were compared using multifactorial repeated measurement ANOVA, followed by Fisher's PLSD post hoc comparisons, if appropriate. Frequencies of compliance profiles were compared via Fisher's exact test. Tidal variations between groups were compared using one-way ANOVA followed by a Student's t test as a post hoc test when indicated. For pixel-wise comparisons of EIT images, Student's t test was performed with Bonferroni correction for multiple comparisons. A P < .05 was considered statistically significant.

| RE SULTS
In the offline analysis, we detected large ventilation leakage in the data of one patient which prevented meaningful analysis of (1) F I G U R E 1 Flow chart. First number of randomization group indicates PEEP before PEEP change, second number of group indicates PEEP after PEEP change. X indicates that PEEP change was performed without recruitment maneuver, R indicates that PEEP change was performed with intermediate recruitment maneuver. PEEP, positive end-expiratory pressure respiratory data. For two patients, we detected violations of the protocol after the measurements. Data from these patients were also excluded from the analyses (Figure 1). Characteristics of the 57 patients included in the study are given in Table 1. All patients were sufficiently ventilated with average oxygen saturation of 99.7 (0.6) % and endtidal CO 2 partial pressure of 38.4 (2.8) mmHg, which were comparable in all ventilation conditions (Table 2).
In four patients hypotension and bradycardia occurred during the first recruitment maneuver and volume substitution was administered, two patients received additionally akrinor (1) or aterenol (1).
No further hemodynamic instabilities were observed.

TA B L E 2 Respiratory variables
The ventral share of ventilation was >55% throughout the measurements in all groups. Tidal variations were comparable between all groups (Table 3).
Impedance gains and losses were significantly different between PEEP increases and PEEP decreases but not between PEEP changes in the same direction with or without intermediate recruitment maneuver (Table 4).

| D ISCUSS I ON
The main results of our study demonstrate that in mechanically ventilated pediatric patients respiratory system compliance is moder- ance nor the derecruitment status nor the regional ventilation was affected by this measure. In a certain point of view, this is in line with earlier studies where we 2 and others 9 also found that signs of tidal derecruitment were more distinct in younger than in older children.
Recruitment maneuvers are supposed to reopen lung tissue that has incrementally derecruited. 10 The reason for the overall missing effect of recruitment maneuvers may be that in the lung healthy pediatric patient such permanently derecruited lung tissue persists only to an irrelevant amount. The respiratory system of pediatric patients is still in development. Particularly, functional residual capacity and closing capacity are in an unfavorable balance promoting tidal derecruitment. 11 This may promote tidal derecruitment but not necessarily permanent atelectasis, persisting at the end of inspiration. Consequently, tidal derecruitment would not be resolvable by moderate PEEP levels-with or without recruitment maneuvers-but might require PEEP levels clearly above 7 cmH 2 O whose applicability in clinical routine are questionable, due to the associated higher peak pressure and the potential side effects of higher PEEP levels on the hemodynamic conditions. However, one might speculate that a certain tidal derecruitment in the pediatric lung is a rather physiological condition without necessity of a countermeasure. In this context, studying the intratidal respiratory system mechanics in spontaneously breathing awake pediatric patients might be interesting but difficult as it would require placement of an esophageal catheter and cooperation of the patient.  Note: First number of group indicates first PEEP level (before PEEP change = T1), second number of group indicates second PEEP level (immediately after PEEP change = T2, and after 20 min ventilation at this PEEP = T3). X indicates that PEEP change was performed without recruitment maneuver, R indicates that PEEP change was performed with intermediate recruitment maneuver. Values represent mean (SD). No significant differences were found between groups at any timepoint.

TA B L E 4
Ventilation gain and loss in ventral and dorsal areas. Significant differences could only be found for different PEEP levels. The intermediate recruitment maneuver had no effect and thus resistive pressure during inspiration was similar, too.
Therefore, we assume that changes in peak pressure paralleled those of plateau pressure. As further the changes of respiratory system compliance were in accordance with the changes of peak pressure, we feel that peak pressure measurements were reliable in our study.

| CON CLUS ION
Lung recruitment maneuvers have limited effects on respiratory system mechanics in healthy children while a moderate increase in PEEP may improve lung compliance.

CO N FLI C T O F I NTE R E S T
The authors report no conflict of interest.