This randomized and controlled trial was performed in the operating theater of a Community Hospital. Ethical approval for this study (IRB #2919/1457/2017) was provided by the Ethical Committee of the Hospital Privado de Comunidad, Mar del Plata, Argentina (ClinicalTrials.gov NCT03141515). Written informed consent was obtained from parents of all subjects participating in the trial. The study started 20 April 2017 and ended 5 January 2018.
Patient’s eligibility criteria
We sequentially recruited patients aged 6 months to 5 years undergoing programmed surgeries. Conditions for enrollment were: need for general anesthesia and mechanical ventilator support, American Physical Status Classification (ASA) I–II and baseline pulse oximetry saturation (SpO2) while breathing room air ≥ 97%. We excluded patients undergoing emergency and thoracic surgeries and patients with pre-existing pulmonary, cardiac or chest wall diseases. After this first selection, we then excluded those patients without LUS evidence of atelectasis after anesthesia induction.
Anesthesia, ventilatory treatment and monitoring
Anesthesia was induced with sevoflurane using a circular system of the GE Aespire workstation (GE Healthcare, Madison, WI, US). Boluses of fentanyl 2 μg kg−1 and vecuronium 0.1 mg kg−1 were added before tracheal intubation with a cuffed endotracheal tube. Anesthesia was maintained with sevoflurane 0.7 minimum alveolar concentration and remifentanyl 0.3–0.5 μg kg−1 min. The lungs were ventilated with a volume control mode using a tidal volume (VT) of 6 mL kg−1, respiratory rate between 20 and 25 bpm, inspiratory-to-expiratory ratio of 1:1.5, 10% of inspiratory pause, PEEP of 5 cmH2O and a FIO2 of 0.5.
Standard EKG, non-invasive mean systemic arterial pressure (MAP), capnography, pulse oximetry and respiratory mechanics were monitored with the S5 device (GE Healthcare/Datex-Ohmeda, Helsinki, Finland). Respiratory flow and pressure signals were obtained by a pediatric mainstream gadget placed at the airways opening, from which peak airways pressure (Pip), dynamic respiratory compliance (Cdyn) and respiratory airways resistance (Rrs) were obtained.
Gas exchange evaluated by the Air-test
Arterial oxygenation was evaluated after anesthesia induction with the Air-test using a pediatric pulse oximeter placed at the thumb (MightySat Rx, Masimo Corporation, Irvine, CA, USA) and decreasing FIO2 from 0.5 to 0.21 during 5 min [10, 11]. Reference SpO2 values breathing air in healthy patients are ≥ 97% and correspond to the anatomical shunt (~ 5–8% of the cardiac output). Any value below 97% is a marker of an additional shunt, presumably due to atelectasis, in those patients who presented baseline SpO2 values ≥ 97% breathing air before anesthesia induction .
LUS was performed with the ultrasound MyLab Gamma device (Esaote, Genova, Italy) using a high-frequency linear probe of 6–12 MHz. Each hemithorax was segmented into six regions using the longitudinal parasternal, anterior and posterior axillary lines and two axial lines, one above the diaphragm and the other 1 cm above the nipples . The ultrasound probe was placed perpendicular to the ribs looking for the standard LUS view, where the pleura and the ventilated lung are visualized between two adjacent ribs (the bat sign) . The probe was placed in the oblique position (along the intercostal spaces between ribs) in the areas where the typical atelectatic consolidations were detected. In general, the posterior zones of the lungs are those with the highest incidence of anesthesia-induced atelectasis [3, 4].
A LUS imaging based aeration score was calculated as previously described for children . Briefly, this score is based on four LUS patterns [13,14,15] investigated in each of the 12 scanned thoracic areas:
Normal aeration (N): presence of the respiratory movement of the lung image relative to the chest wall (lung sliding) and the horizontal artifacts generated by repetition of the linear image of the pleura at regular intervals (A lines), with absence of sub-pleural ultrasound parenchymal signs (B-lines or consolidations).
Moderate loss of lung aeration (B1): presence of vertical dynamic lines, originating from the pleural line or from small sub-pleural consolidations, reaching the lowest edge of the screen (B-lines).
Severe loss of lung aeration (B2): multiple coalescent B-lines giving the aspect of a “white lung”, when the B-lines are so intense and numerous to occupy the whole image.
Complete loss of aeration (C): atelectasis, defined as localized sonographic consolidation, i.e., sub-pleural images with a tissue-like or hypoechoic pattern. Air bronchograms may be observed as bright echogenic branching structures within the consolidated area.
For a given thoracic area, points were allocated to the worst LUS pattern observed: N = 0, B1 = 1, B2 = 2 and C = 3. The LUS aeration score was calculated by the sum of points obtained in all the 12 lung areas, thus ranging from 0 to 36. Progressive increase of the score corresponds to loss of lung aeration.
After tracheal intubation atelectasis areas were diagnosed by LUS examination, consequences on arterial oxygenation were assessed by performing the Air-test (Fig. 1, T1). Patients without LUS evidence of atelectasis were excluded. Patients with atelectasis were randomized into two groups using a computerized randomization table (StatsDirect v 2.7.2; Altrincham, Cheshire, United Kingdom) by an independent and blinded operator:
Control group (C group, n = 20). Ventilation was turned to pressure control ventilation using a fixed driving pressure of 12 cmH2O. PEEP was increased from 5 to 10 cmH2O along 3 min maintaining the supine position during the whole protocol time.
Postural-recruitment maneuver group (P-RM group, n = 20). Ventilation was turned to pressure control ventilation using a driving pressure of 12 cmH2O and PEEP of 10 cmH2O, but they were immediately and sequentially placed: (1) in the left lateral position (90 s), (2) in the right lateral position (other 90 s), (3) back to the supine position (Fig. 1).
After 3′ maneuver, both groups returned to baseline ventilation adding 8 cmH2O of PEEP to maintain eventually the recruitment effect. Five minutes later patients were evaluated by LUS at T2 (Fig. 1). The same investigator non-blinded to treatment groups repeated LUS at each step. Respiratory data and hemodynamic parameters were collected at each protocol step.
The null hypothesis was that lung aeration score would be similar between groups. Considering a beta-power of 80% and an alpha-error of 5% the statistical power to reject this hypothesis was calculated assuming that atelectasis would be present in 90% of patients in the C group and in only 45% of patients in the RM group . A sample size of 20 patients per group was estimated. Univariate comparisons were performed between and within groups applying the Student’s t test. Multiple linear mixed models were adjusted to explain changes in LUS, respiratory and hemodynamic variables related to six predictive factors: age, gender, weight, surgery duration, Air-test and treatment group (fixed effects). The main factor to be analyzed was the proposed treatment.
Data are presented as n (%) for proportions and mean ± SD or median for continuous variables. A p-value < 0.05 was considered statistically significant. All calculations were performed using the R statistical package (R Core Team, 2015, Foundation for Statistical Computing, Vienna, Austria).