Utility of Perioperative Lung Ultrasound in Pediatric Cardiac Surgery: A Randomized Controlled Trial

PEDIATRIC patients are at risk for developing respiratory insufficiency after cardiac surgery because of diminished respiratory reserve.¹  Furthermore, ventilatory failure may arise from several causes such as the effects of general anesthesia, median sternotomy incision, use of cardiopulmonary bypass (CPB), cooling for myocardial protection, anomalies in gas exchange, alterations in lung mechanics, neuromuscular incompetency, and impaired respiratory muscle energetics.^2,3  Pulmonary complications are associated with high morbidity and mortality, increased healthcare costs, and lengthened hospital stay.⁴  Given that anesthetic management can cause, aggravate, or ameliorate pulmonary complications, optimizing perioperative respiratory care is crucial for improving outcomes after pediatric cardiac surgery.

Lung ultrasound has been gaining consensus as a noninvasive, radiation-free tool for diagnosing various pulmonary diseases in adult and pediatric patients.^5–8  Evidence supporting lung ultrasound use is expanding beyond emergency and critical care settings to perioperative care.^9–11  The performance of lung ultrasound approaches that of computed tomography and surpasses that of chest x-ray for diagnosing lung pathologies including consolidation, pleural effusion, pulmonary edema, and pneumothorax,⁷  which occur frequently after cardiac surgery. Considering that pediatric patients are more sensitive to radiation hazards, position changes, and patient transfers, lung ultrasound would be a favorable perioperative option in pediatric cardiac surgery. Nevertheless, there are no guidelines or recommendations for lung ultrasound use in pediatric cardiac surgery.

We hypothesized that perioperative lung ultrasound examinations followed by interventions according to the lung ultrasound findings would benefit pediatric patients undergoing cardiac surgery with CPB and improve clinical outcomes. The objective of this study was to assess the utility of perioperative lung ultrasound and effect of ultrasound-guided recruitment maneuver in pediatric cardiac surgery.

This study was designed as a randomized, controlled, single-blinded, superiority trial. The study was performed at the Seoul National University Hospital, Korea, between August 2015 and August 2016. The study protocol was approved by the Seoul National University Hospital Institutional Review Board (August 20, 2015/No.1507-062-687). The study team evaluated eligibility of patients, obtained written informed consent from parents, and enrolled the participants by individually approaching them before surgery. The inclusion criteria were pediatric patients age 5 yr old or younger who were scheduled for cardiac surgery of acyanotic congenital heart disease. The exclusion criteria were previous thoracic surgery; upper or lower airway infection; airway anomaly; pulmonary disease; genetic disease; abnormal preoperative chest x-ray findings including atelectasis, pneumothorax, pleural effusion, or pneumonia; and preoperative oxygen saturation measured by pulse oximetry (Spo₂) of 97% or less with room air.

Patients were allocated by a simple randomization to either a control or intervention group at an allocation ratio of 1:1 using computer-generated randomization software (http://www.randomization.com; accessed August 24, 2015). Group allocations were concealed in sequentially numbered, opaque, sealed envelopes, which were opened by a member of the study team after inducing general anesthesia. Each envelope contained the group allocation with instructions for the attending anesthesiologist.

An intravenous route was established before bringing the patient to the operating room. Standard monitoring for cardiac surgery included electrocardiography, Spo₂, noninvasive blood pressure, invasive arterial blood pressure, central venous pressure, rectal and nasal temperatures, cerebral near-infrared spectroscopy, and transesophageal echocardiography. All patients underwent an institutionalized general anesthetic protocol that included preoxygenation with 100% oxygen; induction with 0.02 mg/kg atropine, 0.1 mg/kg midazolam, 4 to 5 mg/kg thiopental sodium, and 5 to 10 µg/kg fentanyl; neuromuscular blockade with 1 mg/kg rocuronium; tracheal intubation with a cuffed endotracheal tube (ETT) of proper size; and maintenance with an air–oxygen mixture.

After tracheal intubation, mechanical ventilation of the lungs was initiated in a volume-controlled mode set to deliver a tidal volume of 8 ml/kg, a positive end-expiratory pressure of 5 cm H₂O, and a fractional inspired oxygen tension (Fio₂) of 0.4. The ventilator was set to deliver 20 to 40 breaths/min depending on the patient’s age¹²  and was adjusted to end-tidal carbon dioxide of 35 to 45 mmHg, with an inspiratory:expiratory ratio of 1:2.

Anesthesia was maintained using 0.1 to 0.2 mg · kg^–1 · h^–1 midazolam, 2.5 to 5 µg · kg^–1 · h^–1 sufentanil, and 0.05 to 0.1 mg · kg^–1 · h^–1 vecuronium. Surgery was performed through a standard median sternotomy and proceeded as per institutional protocol. During sternotomy, the lungs were temporarily deflated to prevent lung injury. When patients were on the CPB, the lungs were completely deflated and not ventilated. While preparing for separation from the CPB, mechanical ventilation was reinitiated as the same setting after tracheal suction and lung inflation in both groups. A subxiphoid mediastinal tube was inserted in the pericardial cavity after successful weaning from the CPB. Intraoperative arterial blood gas (ABG) analyses were performed three times: after induction of anesthesia, after weaning from CPB, and after sternal closure.

After the surgery, all patients were transferred to the pediatric intensive care unit without reversing the neuromuscular blockade. During the transfer, patients were ventilated with 100% oxygen by anesthesiologists blinded to the randomization result. In the pediatric intensive care unit, patients were mechanically ventilated in a pressure-regulated volume-controlled mode to deliver a tidal volume of 10 ml/kg, a positive end-expiratory pressure of 5 cm H₂O, a Fio₂ of 0.6, and a respiratory rate of 20 to 40 breaths/min with an inspiratory:expiratory ratio of 1:2. The setting was adjusted by surgeons who were blinded to the randomization result. Postoperative laboratory and chest x-ray examinations were performed immediately, 3 h, and 6 to 12 h after admission to the pediatric intensive care unit. The decision regarding when to extubate or transfer to the general ward was made by the surgeons in the pediatric intensive care unit. The criteria for extubation were Pao₂/Fio₂ ≥ 200 from ABG (Pao₂ 80 mmHg on Fio₂ 0.4) with an adequate level of consciousness, spontaneous respiration, and hemodynamic stability. The criteria for pediatric intensive care unit discharge were stable hemodynamics and rhythm without inotropic support, appropriate ventilation and oxygenation without mechanical ventilatory support, and adequate diuresis and mentation.

During the intraoperative and postoperative period, the same Spo₂ sensor (Nellcor with OxiMax Technology Neonatal/Adult or Infant Adhesive Spo₂ sensor, Covidien, USA) and monitoring device (Solar 8000M/i patient monitor, GE Medical Systems, USA) were used in the operating room and pediatric intensive care unit. According to the manufacturer, the accuracy of the Spo₂ monitor was 1.5% for the Spo₂ range of 90 to 100%, 2.1% for 80 to 89.9%, and 2.4% for 60 to 79.9%. Desaturation cutoff was set as Spo₂ < 95%.¹² 

Lung ultrasound examination was performed twice in the control group and three times in the intervention group. Only the intervention group underwent lung ultrasound examination 1 min after initiating mechanical ventilation of the lungs after tracheal intubation (designated as preoperative lung ultrasound examination). Both groups underwent lung ultrasound examination at the end of surgery (designated as postoperative lung ultrasound examination) and 6 to 12 h after surgery in the pediatric intensive care unit (designated as pediatric intensive care unit lung ultrasound examination).

All ultrasound scans were performed by the same anesthesiologist, who had an experience of 100 or more lung ultrasound scans in pediatric patients, using Logiq e US (GE Healthcare, USA) with a 4- to 10-MHz linear transducer. Patients were scanned in the supine position according to the lung ultrasound examination method described by Acosta et al.¹³  Each hemithorax was divided into six regions using three longitudinal lines (parasternal, anterior, and posterior axillary) and two axial lines (one above the diaphragm and the other 1 cm above the nipples). The 12 lung regions were sequentially scanned from right to left, cranial to caudal, and anterior to posterior. Each region was assessed using a two-dimensional view with the probe placed parallel to the ribs and was evaluated for the following signs: the lung “sliding” sign, A-lines, B-lines, consolidation, air-bronchograms, pleural effusion, and pneumothorax.

The degree of consolidations and B-lines was scored from 0 to 3 following the grading method described by Song et al.¹⁴  The degree of pleural effusion was divided into four grades and scored from 0 to 3: 0, no pleural effusion; 1, minimal pleural effusion; 2, a small amount of pleural effusion; and 3, a moderate amount of pleural effusion.¹⁵  Representative lung ultrasound findings are shown in figure 1. The worst ultrasound abnormality detected was considered as the characterization for the region examined, and video clips of each region were stored. The degree of consolidations, B-lines, and pleural effusions were separately scored for each region and were summed for analysis.

In the intervention group, a recruitment maneuver was performed after each lung ultrasound examination if there was significant atelectasis, defined as a consolidation score of 2 or greater in any region.¹⁴  Under real-time ultrasound guidance, a 5-cm H₂O stepwise increase in airway pressure from 10 cm H₂O with an Fio₂ of 0.4 was manually applied until no collapsed lung areas were visible on the ultrasound. Each level of continuous positive airway pressure was applied for 5 s. The maximum airway pressure was limited to 40 cm H₂O. After applying the lung ultrasound-guided recruitment maneuver once, the same ventilator setting was maintained. The timeline of the lung ultrasound examination and lung ultrasound-guided recruitment maneuver performed in each group is illustrated in figure 2.

The following data were collected for every patient: age, height, weight, sex, diagnosis, pre- and postoperative chest x-ray findings, duration of anesthesia, number of intra- and postoperative (within 24 h) desaturation (Spo₂ < 95%) events, intra- and postoperative (within 24 h) ABG results, duration of mechanical ventilation, and length of pediatric intensive care unit stay. The primary outcomes were the incidences of intraoperative desaturation, postoperative (within 24 h) desaturation, and postoperative (within 24 h) pulmonary complications. Postoperative pulmonary complications were defined as respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis following the description by Gallart and Canet.¹⁶  The secondary outcomes included the incidence of desaturation during transfer to pediatric intensive care unit, number of intra- and postoperative desaturation events, initial Spo₂ upon arrival to the pediatric intensive care unit, duration of mechanical ventilation, length of pediatric intensive care unit stay, incidence of postoperative fever (body temperature ≥ 37.5°C within 24 h), intra- and postoperative (within 24 h) ratio of arterial oxygen partial pressure to Fio₂ (Pao₂/Fio₂) from ABG, and lung ultrasound scores of consolidations, B-lines, and pleural effusion on the postoperative and pediatric intensive care unit lung ultrasound examinations. Hemodynamic deterioration (greater than or equal to 20% baseline) during the recruitment maneuver was recorded.

Because there were no previous studies investigating the effect of perioperative lung ultrasound in patients undergoing cardiac surgery, the sample size was calculated from previous data obtained in pediatric patients.¹⁷  Considering that the incidence of intraoperative hypoxemia was 20% in pediatric patients undergoing general anesthesia, we assumed that performing the perioperative lung ultrasound and lung ultrasound-guided recruitment maneuver would decrease it to 5%. The required sample size was 61 for each group, with a set α error of 0.05, a power of 80%, and a dropout rate of 10%.

All data are expressed as the mean ± SD or median (interquartile range [range]) unless otherwise specified. The Kolmogorov-Smirnov test was used to determine the normality of the distribution. The primary outcomes were evaluated using the chi-square test. The secondary outcomes were evaluated using the Student’s t test and chi-square test for the continuous and categorical variables, respectively. The Mann–Whitney U test was used for comparison of the initial Spo₂ upon arrival to pediatric intensive care unit and lung ultrasound scores between the groups. The Wilcoxon signed-rank test was used for comparison of the intragroup lung ultrasound scores.

Although the adjustment for multiple primary outcomes was not included in the original analysis plan, it was requested during the peer review process. In order to adjust the multiplicity of primary outcomes, the Bonferroni correction was applied. Regarding three primary outcomes, P ≤ 0.017 was considered to be statistically significant. These adjustments were post hoc and were offered in attempt to conservatively interpret the primary inference. Statistical analysis was performed using IBM SPSS Statistics 23 (SPSS Inc., IBM Corp., USA).

From August 25, 2015, to August 22, 2016, 122 children were enrolled and randomized into the control (n = 61) and intervention (n = 61) groups, respectively (fig. 3). Two patients in the intervention group were excluded from the final analysis because pediatric intensive care unit lung ultrasound examination could not be performed. Baseline characteristics of the study population and perioperative variables are summarized in table 1.

Among three primary outcomes, the incidence of postoperative desaturation was higher in the control group than in the intervention group (64% vs. 27%; P < 0.001; OR, 0.210; 95% CI, 0.097 to 0.456). However, the incidences of intraoperative desaturation (36% vs. 19%; P = 0.033; OR, 0.406; 95% CI, 0.176 to 0.939) and postoperative pulmonary complications (12% vs. 3%; P = 0.093; OR, 0.271; 95% CI, 0.054 to 1.361) were similar between the control and intervention groups.

Other perioperative outcome variables are summarized in table 2. In the intervention group, 55 (93%) patients on the preoperative lung ultrasound examination, 25 (42%) patients on the postoperative lung ultrasound examination, and 50 (85%) patients on the pediatric intensive care unit lung ultrasound examination received a lung ultrasound-guided recruitment maneuver. The incidence of desaturation during transfer to the pediatric intensive care unit was similar between the control and intervention groups (5% vs. 0%; P = 0.244; OR, 0.951; 95% CI, 0.898 to 1.007). Although the length of pediatric intensive care unit stay did not show a difference between the groups (67 ± 62 vs. 53 ± 37; 95% CI of mean difference, –5 to 32; P = 0.145), the duration of mechanical ventilation was significantly shorter in the intervention group than in the control group (38 ± 43 vs. 26 ± 25; 95% CI of mean difference, 0 to 25; P = 0.048). The incidence of postoperative fever did not differ between the groups (62% vs. 71%; P = 0.337; OR, 1.495; 95% CI, 0.696 to 3.214).

The intra- and postoperative Pao₂/Fio₂ values are summarized in table 3. All Pao₂/Fio₂ values were significantly higher in the intervention group than in the control group.

The lung ultrasound scores of consolidations, B-lines, and pleural effusion are summarized in table 4. The lung ultrasound scores of consolidations and B-lines on the postoperative and pediatric intensive care unit lung ultrasound examination were significantly lower in the intervention group than in the control group. In the intervention group, the lung ultrasound scores of consolidations and B-lines significantly decreased between the pre- and postoperative lung ultrasound examinations. Nonetheless, in both groups, the lung ultrasound scores of consolidations and B-lines significantly increased between the postoperative and pediatric intensive care unit lung ultrasound examinations.

Preoperative lung ultrasound examination detected an abnormal ETT placement in the intervention group. Moreover, in the control group, postoperative and pediatric intensive care unit lung ultrasound examinations discovered significant pleural effusion that needed a chest tube insertion and minimal pneumothorax, respectively. No complications such as hypotension, arrhythmia, or lung injury were associated with the recruitment maneuver.

In this study, we investigated the utility of perioperative lung ultrasound examinations in pediatric patients undergoing cardiac surgery. Perioperative lung ultrasound examinations accompanied by lung ultrasound-guided recruitment maneuvers proved useful for decreasing postoperative desaturation events, improving lung ultrasound findings, and shortening the duration of mechanical ventilation.

Despite several reports regarding the use of lung ultrasound for diagnosing and managing various diseases in pediatric patients, including respiratory distress syndrome, pneumonia, bronchiolitis, and atelectasis,^18–21  data concerning the use of lung ultrasound in cardiac surgery are limited in adult and pediatric populations. Especially in children, there have been only case reports regarding the use of lung ultrasound in cardiac surgery.^10,22  To the best of our knowledge, this is the first randomized controlled trial investigating the use of lung ultrasound and the effect of lung ultrasound-guided recruitment maneuvers according to the lung ultrasound findings in pediatric cardiac surgery.

Alsaddique et al.¹¹  recently demonstrated that routine repeated monitoring with cardiac and lung ultrasound after cardiac surgery in adults is feasible and that it alters clinically important diagnoses. In our study, lung ultrasound examination with recruitment maneuver played a key role in improving perioperative respiratory care not only by eliminating atelectasis but also by discovering abnormal conditions such as misplaced ETT, pleural effusion, and pneumothorax.

Compared with the findings of de Graaff et al.,¹⁷  that the incidence of intraoperative hypoxemia (Spo₂ ≤ 90%) was 20% in pediatric noncardiac surgery, the overall incidence of intraoperative desaturation was 28% (36% in the control group vs. 19% in the intervention group) in this study despite a stricter definition (Spo₂ < 95%). Moreover, the overall incidence of postoperative desaturation was 46% (64% in the control group vs. 27% in the intervention group), which was higher than that of adults,²³  reconfirming that pediatric patients undergoing cardiac surgery are vulnerable to pulmonary complications. Therefore, perioperative respiratory care is essential in pediatric cardiac surgery.

We found no difference in the incidence of intraoperative desaturation (P = 0.033) between the groups. However, when interpreting our results, one should consider that we applied conservative statistics to adjust multiple primary outcomes (P ≤ 0.017), as we mentioned in Materials and Methods. The incidences of intra- and postoperative desaturation were reduced by more than half between the groups by performing perioperative lung ultrasound examinations and lung ultrasound-guided recruitment maneuvers according to the lung ultrasound findings.

Patients in the control group experienced 2.5 times greater numbers of intraoperative desaturation events compared with those in the intervention group. Most of the desaturation events occurred during the sternotomy when the lungs were deflated (73%), and the rest occurred during the weaning from CPB in the control group. Conversely, in the intervention group, the desaturation percentage during sternotomy (55%) was much smaller, implying that a preoperative lung ultrasound examination with recruitment maneuver may have contributed to atelectasis resolution, occurring after the induction of anesthesia, and to better alveolar aeration. Furthermore, the number of postoperative desaturation events in the control group was five times greater than that in the intervention group, and three of these patients had 10 or more events, indicating that not only the incidence but also the intensity of desaturation differed between the groups.

Because the lungs were deflated while on CPB, that could have brought equilibration in the state of the lungs between the groups regardless of any benefit gained by the preoperative lung ultrasound examination with recruitment maneuver. Nevertheless, the intervention group showed better lung ultrasound scores in the postoperative lung ultrasound examination. Pulmonary dysfunction attributed to CPB is thought to arise from the effects of acute systemic and pulmonary inflammatory response.²⁴  In addition, the cessation of ventilation during CPB results in collapsed lungs leading to insufficient alveolar distention to activate the production of surfactant, which potentiates alveolar collapse and atelectasis.²⁴  In this context, pre-CPB collapsed lungs in the control group could have contributed to the inflammatory response and subsequent reactions, causing unfavorable results after CPB.

The focus of pediatric cardiac surgery has changed from saving lives to reducing morbidity and optimizing quality of life.²⁵  Hence, concepts such as early extubation and reduction in the intensive care unit or hospital stay are being investigated. Evidence regarding early extubation after pediatric cardiac surgery has established that the technique is safe and without additional morbidity or mortality, if applied in the right setting to the right population.^26–31  The lung ultrasound examination with recruitment maneuver in our study shortened the duration of mechanical ventilation, supporting the current trend and influencing the length of pediatric intensive care unit stay. The approximately 13-h difference for the duration of mechanical ventilation between the groups could be linked to the difference in the length of pediatric intensive care unit stay, although this was not significant. Our institution is currently practicing extubation in the operating room for eligible cases, and we believe the role of lung ultrasound would be more important in these “fast-track” cases.

Advantages of the recruitment maneuver for preventing postoperative pulmonary complications in patients undergoing general anesthesia have been demonstrated in numerous reports.^32–34  Among several ways of performing recruitment maneuver, we used a sustained inflation method because of its easy applicability in the operating room setting. Given that the recruitment maneuver may cause complications such as hypotension,^35–37  it is important to apply the recruitment maneuver carefully. In this study, real-time ultrasound guidance was applied to individualize the recruitment maneuver depending on the lung ultrasound findings. However, whether the lung ultrasound-guided recruitment maneuver is better than the recruitment maneuver without lung ultrasound needs to be verified in further studies.

Pleural effusions are significant complications after pediatric cardiac surgery, with a reported incidence ranging between 25 and 39%.^38–40  In this study, the overall incidence of more than a small degree of pleural effusion was 14%, which was lower than those previously reported, probably because the study subjects underwent relatively simple cardiac surgeries.

Several reports in adults have highlighted the importance of recognizing and preventing postoperative pulmonary complications after cardiac surgery,^3,24,41  which cannot be overemphasized in pediatric cardiac surgery, either. Given that repeated examinations are inevitable, the lung ultrasound examination with recruitment maneuver would be a suitable tool for pediatric patients after cardiac surgery, enabling point of care at the bedside. Considering that we enrolled only pediatric patients with acyanotic congenital heart disease, generalization of our results to other populations such as children with cyanotic congenital heart disease or preterm neonates should be made cautiously.

There are several limitations in this study. First, the anesthesiologist who performed the lung ultrasound examination was not blinded, which might have influenced the outcome measurements. Nonetheless, the designated anesthesiologist only performed the lung ultrasound examination and lung ultrasound-guided recruitment maneuver. Second, because the surgeons managed the patients postoperatively, inconsistency in management plans between the surgeons could have affected the results. Third, as this study aimed to assess the utility of perioperative lung ultrasound in pediatric cardiac surgery, we focused on the intraoperative period until the first postoperative day. However, some outcome variables could have been influenced by events 24 h after surgery.

Perioperative lung ultrasound examinations accompanied by lung ultrasound-guided recruitment maneuvers proved practical and beneficial to pediatric patients undergoing cardiac surgery. They decreased the incidence of postoperative desaturation events and shortened the duration of mechanical ventilation, encouraging more active application in pediatric cardiac surgery.

Support was provided solely from institutional and/or departmental sources.

The authors declare no competing interests.

Full protocol available at: jintae73@snu.ac.kr. Raw data available at: jintae73@snu.ac.kr.