CT 3-Dimentional Airway Reconstruction-guided Intraluminal Placement of Endobronchial Blocker in Pediatric Patients: A Randomized Controlled Study

Background: The one-lung ventilation (OLV) with endobronchial blocking is commonly used in anesthesia for pediatric thoracic surgery. Bronchoscopy is commonly used to guide the endobronchial blocker placement. However, when bronchoscopy is not applicable, the proper placement of endobronchial blocker is challenging. The computed tomography (CT) 3-dimentional reconstruction may be used to accurately measure the airway of pediatric patients. The present study was aimed to propose a new approach of CT 3-dimentional airway reconstruction-guided endobronchial blocker placement in pediatric patients and to determine its eciency in clinical application. Methods: A total of 127 pediatric patients of 0.5-3 years old who would undergo elective thoracic surgery under OLV were randomized into the bronchoscopy group and the CT group. The degree of lung collapse, postoperative airway mucosal injury, pulmonary infection within 72 h after surgery, trachyphonia after tracheal extubation, durations of postoperative mechanical ventilation, intensive care unit (ICU) stay, and hospitalization, the successful rate of the rst blocker positioning, and the required time and repositionings for successful blocker placement were compared between the two groups. Results: The degree of lung collapse, postoperative airway mucosal injury, pulmonary infection within 72 h after surgery, trachyphonia after tracheal extubation, durations of postoperative mechanical ventilation, ICU stay, and hospitalization were similar between the two groups (all P > 0.05). Conclusions: For pediatric patients who would undergo surgery with OLV, preoperative CT 3-dimentional airway reconstruction could be used to guide endobronchial blocker placement, with a blocking eciency similar to that of bronchoscopy-guided blocker placement. anatomy is different between children and adults. In addition, the existence of abnormal take off of the right upper lung lobe makes the endobronchial blocker placement in the right bronchus harder than that in the left bronchus. Whether chest CT images could be used to guide endobronchial blocker placement in pediatric patients remains to be determined. We proposed a novel method of applying CT 3-dimentional reconstruction to measure the airway and guide endobronchial blocker placement in pediatric patients. In the present randomized prospective study, we compared the eciency of endobronchial blocker placement guided by bronchoscopy and CT 3-dimentional reconstruction and determined the feasibility of applying preoperative helical CT 3-dimentional airway reconstruction to guide endobronchial blocker placement in pediatric patients.


Introduction
During anesthesia for thoracic surgery, one-lung ventilation (OLV) is very important because lung isolation is necessary for most thoracic surgeries to ensure clear surgical exposure 1,2 . For pediatric patients, several OLV techniques are available, including double-lumen tube and bronchus blocking 3 .
However, conventional double-lumen tube and UniventTM blocker are not suitable for infants and young children due to their large external diameters 4 , whereas the double-lumen tube (Marraro) designed for newborns and infants are not widely adopted yet 5 . Bronchial blocking is the most commonly used OLV technique for pediatric patients. Quick and proper blocker placement is the key of OLV, and bronchoscopy (BRO) is commonly used to guide endobronchial blocker placement in pediatric patients 6 . The blocking techniques include intraluminal and extraluminal blocking. For extraluminal blocking, the bronchial blocker and Tracheal tube need to be inserted together through the glottis and may cause airway mucosal injury with a high rate of postoperative traumatic laryngitis, and the bronchial blocker is hard to be xed and is prone to move during surgery 7,8 . Intraluminal blocking causes less injury with certain blocking e ciency, but the application of bronchoscopy-guided positioning is limited by the diameter of the Tracheal tube for pediatric patients 9 . Only the Tracheal tube with an internal diameter greater than 4.5 mm could allow the simultaneous insertion of the bronchoscope and the nest bronchial blocker.
Bronchoscopy-guided intraluminal blocking cannot be applied in pediatric patients who are too young or have a narrow airway that cannot allow the insertion of a Tracheal tube with an internal diameter greater than 4.5 mm. In addition, for institutions without beroptic bronchoscopy, such as some institutions in developing countries, how to properly place the endobronchial blocker in pediatric patients remains challenging.
Chest CT images could be used to accurately predict the optimal insertion depth of double-lumen Tracheal tube 10 and guide extraluminal Uniblocker placement in the left bronchus in adult patients 11 .
However, the airway anatomy is different between children and adults. In addition, the existence of abnormal take off of the right upper lung lobe makes the endobronchial blocker placement in the right bronchus harder than that in the left bronchus. Whether chest CT images could be used to guide endobronchial blocker placement in pediatric patients remains to be determined. We proposed a novel method of applying CT 3-dimentional reconstruction to measure the airway and guide endobronchial blocker placement in pediatric patients. In the present randomized prospective study, we compared the e ciency of endobronchial blocker placement guided by bronchoscopy and CT 3-dimentional reconstruction and determined the feasibility of applying preoperative helical CT 3-dimentional airway reconstruction to guide endobronchial blocker placement in pediatric patients.

Methods
Patient enrollment and randomization: This study was approved by the institutional ethical committee of Guangzhou Women and Children's Medical Center (No. 2014051229, approval date: June 3, 2014). The trial was registered prior to patient enrollment at China Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=4344, Principal investigator: Yingyi Xu, Registration number: ChiCTR-TRC-14005232, Date of registration: 12 August 2014). Written informed consent was obtained from all patients enrolled in the study. Informed consent was signed by the guardians of each patient. Pediatric patients who would undergo elective thoracic surgery between September 2014 and June 2016 at Guangzhou Women and Children's Medical Center were selected. The enrollment criteria were as follows: (1) ASA stage I-III and (2) age of 0.5-3 years old. The exclusive criteria were as follows: (1) airway compression; (2) laryngeal edema or acute airway in ammation; (3) abnormal takeoff of the right upper lung lobe; (4) foreseeable di culties in endotracheal intubation. The enrolled patients were randomized into the bronchoscopy (BRO) group and the CT group using the closed envelope technique. The endobronchial blocker placement was guided by bronchoscopy in the BRO group and by CT 3dimentional airway reconstruction in the CT group. All cases of anesthesia were performed by a pediatric anesthetist with 6-year experience of thoracic anesthesia. Random numbers were generated using software (SAS 9.2, SAS Institute Inc, Cary, NC, USA) with a ratio of 1:1. These numbers were then sealed in envelopes and kept by an independent study coordinator who did not participate in anaesthesia, perioperative care and postoperative follow-up of the patients. During the study period, patients were consecutively recruited and randomly divided into the control or intervention group accordingly.
Anaesthesiologists who gave anaesthesia did not participate patients' follow up and data collection. Patients, healthcare providers and investigators who were in charge of follow-up and data collection, were blinded to the study protocol.
CT measurement: All pediatric patients received cervical and chest CT scanning (5 mm thickness, 5 mm interval, Aquilion 64, Toshiba) under sedation at the supine position for 3-dimentional airway reconstruction before surgery. The FH plane was determined with the bilateral auriculares and the orbitale; the median vertical plane was determined with the middle of sella turcica, the nasospinale, and the posterior edge of foramen magnum. The distance from the incisor teeth to the carina was measured at the vertical plane when the airway between the incisor teeth and the carina was clearly exposed ; if the patient was not at a proper position or the airway was compressed, the distance would be measured after surface reconstruction ( Figure 1).
Anesthesia: All pediatric patients received intravenous injection of 0.01 mg/kg penehyclidine hydrochloride before surgery and oxygen inhalation after entering the operation room. They received micro-pump infusion (8-10 ml/kg/h) of sodium acetate Ringer's injection, and their BP, HR, ECG, and SpO 2 were monitored. Midazolam (0.05 mg/kg), sufentanil (0.3 μg/kg), and rocuronium (0.6 mg/kg) were injected intravenously to induce general anesthesia. Then, an tracheal tube without side holes (Weili Medical Inc, Guangzhou, China) was intubated under direct vision of laryngoscopy. The catheter model was selected according to the calculation using the classic formula (based on predicted age formula).
After intubation, the partial pressure of carbon dioxide in endexpiratory gas (PETCO 2 ) as well as invasive arterial blood pressure and central venous pressure were monitored, and tracheal aspiration was performed. Inhalation of 1%-3% sevo urane was used for anesthesia maintenance with a tidal volume of 6-8 ml/kg. The concentration of sevo urane was adjusted according to hemodynamic changes and data of anesthesia monitoring. Rocuronium and sufentanil were supplemented while necessary. All patients were subjected to ICU care after surgery.
Endobronchial blocker placement: In the BRO group, the insertion depth of tracheal tube was calculated using the classic formula 12 . After the 5 French (5F) Weili endobronchial blocker (Weili medical Inc, Guangzhou, Guangdong, China) was placed into the tracheal tube, an electrobronchoscope (A20-2.8, Maidehao Co, Zhuhai, Guangdong, China) with a diameter of 2.8 mm was inserted to help locate the endobronchial blocker until the point A of endobronchial blocker reached the take off of the main bronchus at the blocking side ( Figure 2). The proper blocker placement was con rmed under bronchoscopy after the patients shifted from the horizontal position to the lateral position.
In the CT group, CT 3-dimentional reconstruction images were used to measure the length of the main bronchus (the length from the incisor teeth to the carina) before endobronchial blocker placement. Before endotracheal intubation, the insertion depth was preset as the CT-measured length of the main bronchus minus 2 cm and was marked (marker 1) on the tracheal tube ( Figure 3a). The endobronchial blocker was inserted through the tracheal tube until the point A of the sacculus reached the catheter tip. The positions on the blocker which paralleled the screw cap (marker 2) and the screw cap plus 2 cm (marker 3) were marked, then the endobronchial blocker was extubated after the cap was screwed up (Figure 3b). The tracheal tube was inserted to marker 1 under direct-vision laryngoscopy. The endobronchial blocker was inserted through the tracheal tube again. The connectors of the endobronchial blocker and the tracheal tube were xed when the screw cap paralleled marker 2. The endobronchial blocker was further inserted until the screw cap paralleled marker 3 with resistance disappeared, and the sacculus was in ated with 1.5-2.5 ml of air (Figure 3c). Both lungs were auscultated to make sure that respiratory sounds disappeared in the lung of the blocking side. If proper blocking was not achieved after 5 consecutive repositionings, bronchoscopy-guided placement would be applied, and the patient would be excluded. The proper blocker placement was con rmed by auscultation after the patients shifted from the horizontal position to the lateral position.
Observational parameters: (1) the required time for successful blocker placement (measured since the endobronchial blocker was inserted through the vocal cord until it was placed at the proper position); (2) the number of repositionings for successful blocker placement (each extubation of the endobronchial blocker from the Tracheal tube was counted as one repositioning); (3) the successful rate of the rst blocker positioning; (4) the degree of lung collapse ranked by the surgeon as excellent (complete lung collapse at the blocking side), fair (lung collapse at the blocking side with a little amount of residual air that would not affect surgical exposure), moderate (partial lung collapse which requires suction or manual collapse), and poor (no collapse of the lung) 13 ; (5) airway mucosal injury graded using bronchoscopy after surgery by an anesthetist as none (no mucosal edema), mild (mild mucosal edema), moderate (obvious mucosal edema and hyperemia), severe (mucosal erosion and hemorrhage) 11 ; (6) pulmonary infection occurred within 72 h after surgery, which was de ned as plaque-like shadow on both lungs with or without pleural effusion observed by chest X-ray; (7) trachyphonia after tracheal extubation; Estimation of sample size: The sample size was estimated with α = 0.05 and 1-β = 0.8 using the PASS 15.0 software (NCSS, Utah, USA). According to our previous clinical experience, the adequacy of lung collapse was similar in the two groups. According to the estimation, at least 61 patients in each group needed to be enrolled to nd a moderate variation (i.e., W = 0.3) between the two groups.
Statistical analyses: The SPSS 15.0 software (NCSS, Utah, USA) was used for statistical analyses. Continuous data with normal distribution are expressed as mean ± standard deviation and were analyzed using the independent-sample t test; continuous data with abnormal distribution are expressed as median (interquartile range) and were analyzed using the Wilcoxon rank-sum test; categorical data are expressed as cases (%) and were analyzed using the Pearson χ 2 test or the χ 2 test with correction for continuity. P < 0.05 was considered signi cant.

Results
A total of 127 pediatric patients were assessed for eligibility. Five patients were excluded due to the abnormal takeoff of the right upper lung lobe; 3 patients withdrew from the study after grouping because one-lung ventilation technique was deemed not necessary by the surgeon. Therefore, 119 patients were enrolled into this study (Figure 4). The two groups had no signi cant differences in demographic characteristics, including age, sex, weight, height, ASA stage, and thoracic surgery type (P > 0.05; Table 1).
The required time for successful blocker placement was signi cantly longer in the CT group than in the BRO group (124.9 ± 34.2 s vs. 92.9 ± 17.6 s, P < 0.001), successful blocker placement required more repositionings in the CT group than in the BRO group (1.22 ± 0.56 vs. 1.05 ± 0.28, P < 0.05), and the successful rate of the rst blocker positioning was signi cantly lower in the CT group than in the BRO group (82.8% vs. 96.7%, P < 0.05) ( Table 2). After blocking, the degree of lung collapse was excellent in 56 patients and fair in 2 patients from the CT group and was excellent in all the 61 patients from the BRO group, without signi cant difference (P > 0.05). After surgery, mild airway mucosal injury was observed in 2 patients from the CT group and 1 from the BRO group (P > 0.05). For both groups, 2 patients had pulmonary infection within 72 h after surgery, and 3 had trachyphonia after tracheal extubation (both P > 0.05). No signi cant differences in the durations of postoperative mechanical ventilation, ICU stay, and hospitalization were observed between the two groups (all P > 0.05).

Discussion
The insertion of the nest 5F endobronchial blocker requires a Tracheal tube with an internal diameter greater than 4.5 mm 14 . While applying OLV in pediatric patients, bronchoscopy cannot be used to guide intraluminal blocker placement if the insertion of a Tracheal tube with an internal diameter greater than 4.5 mm is not applicable. In the present study, we used chest CT 3-dimentional reconstruction to measure the airway and guide endobronchial blocker placement.
While comparing the techniques used for lung isolation, safety and e ciency should be considered. The adequacy of lung collapse affects surgical exposure and is a criterion for the assessment of successful OLV 15 . In the present study, CT-guided endobronchial blocker placement achieved similar adequacy of lung collapse as compared with bronchoscopy-guided blocker placement in pediatric patients. The sacculuses of most endobronchial blockers are featured by small volume and high pressure, and excessive in ation may induce pressure mucosal injury; during sacculus in ation procedures, the advantage of direct vision under bronchoscopy was considered to be important for the prevention of sacculus in ation-caused mucosal injury in small bronchi 16 . However, in the present study, no signi cant difference in airway mucosal injury was observed between the BRO and CT groups, suggesting that CTguided endobronchial blocker placement would not increase the risk of airway mucosal injury. In addition, the rates of postoperative pulmonary infection and trachyphonia were similar in the two groups (P > 0.05). Regarding postoperative pulmonary recovery, no signi cant differences in the durations of mechanical ventilation, ICU stay, and hospitalization were observed between the two groups. Therefore, we consider that using CT 3-dimentional airway reconstruction to guide endobronchial blocker placement is feasible and safe.
We postulated that CT 3-dimentional reconstruction may be used to accurately estimate the insertion depth of Tracheal tube before blocking. The distance from point A to point B on the tip of endobronchial blocker is approximately 2 cm. Inserting the uncuffed Tracheal tube without side holes to 2 cm above the carina would leave enough space to allow the insertion of endobronchial blocker for laterobronchus blocking 17 . In addition, by checking the markers on the endobronchial blocker during insertion, we could determine the optimal insertion depth in the bronchus of the blocking side. Therefore, CT 3-dimentional reconstruction-guided endobronchial blocker placement can be used for quick intraluminal blocking. Narayanaswamy et al. 18 reported that the median time to complete the placement procedures under the guidance of beroptic bronchoscopy was 203 seconds, whereas Campos et al. 13 reported a duration of 158 seconds. Peng et al. 19 reported that the placement time was 185 seconds. In the present study, it was 92.9 s in the BRO group and 124.9 s in the CT group, both were much shorter than those reported in literature. It may be explained by that endobronchial blocking was performed by anesthetists with 6-year experience of thoracic anesthesia in our center, who were skilled in performing both endobronchial blocking and bronchoscopy 20 . In the present study, the required time was longer in the CT group than in the BRO group because CT-guided blocker placement required the assistance of auscultation, costing longer time than placing the blocker under direct vision through bronchoscopy.
The present study contained some limitations. First, the major limitation was that the adequacy of lung collapse relied on surgeons' subjective assessment. Second, this was a single-center study, and the feasibility of using CT 3-dimentional airway reconstruction to guide endobronchial blocker placement needs to be validated in future multi-center studies. Third, pediatric patients with abnormal takeoff of the right upper lung lobe were excluded. The application of CT-guided endobronchial blocker placement in these patients needs further investigation.
In conclusion, comparing with bronchoscopy-guided endobronchial blocker placement, CT-guided blocker placement achieved similar adequacy of lung collapse. Although CT guidance may increase the required time and repositionings for successful blocker placement, it will not increase bronchus mucosal injury and affect postoperative pulmonary recovery. Therefore, for pediatric patients who need to undergo surgery with OLV, CT 3-dimentional airway reconstruction is a simple and e cient technique for endobronchial blocker placement.  Figure 1 The measure for the distance from the incisor teeth to the carina.

Figure 2
The process to locate the bronchial blocker(The BRO group).

Figure 3
The process to locate the bronchial blocker(The CT group).