BACKGROUND: Effective lung collapse of the nonventilated lung can facilitate thoracic surgery. Previous studies showed that using a bronchial blocker could delay the time of lung collapse compared with using a double-lumen endotracheal tube. We hypothesized that the use of nitrous oxide (N2O) in the inspired gas mixture during 2-lung ventilation would lead to clinically relevant improvement of lung collapse during subsequent 1-lung ventilation with a bronchial blocker.
METHODS: Fifty patients were randomized into 2 groups: N2O (n =26) or O2 (n = 24). The N2O group received a gas mixture of oxygen and N2O (FIO2 = 0.5), and the O2 group received 100% oxygen until the start of 1-lung ventilation. Lung isolation was achieved with an Arndt® wire-guided bronchial blocker (Cook® Critical Care, Bloomington, IN. After turning patients to the lateral decubitus position, the cuff of the bronchial blocker was inflated under fiberoptic bronchoscopy surveillance, and thereafter, the dependent lung was ventilated with 100% oxygen during 1-lung ventilation in both groups. Surgeons blinded to the randomization evaluated the degree of lung collapse by using a verbal rating scale (lung collapse scale, 0 = no collapse to 10 = complete collapse) at 5 minutes after opening the pleura. Also, as secondary outcomes, lung collapse at 1 and 10 minutes were evaluated.
RESULTS: The score on the lung collapse scale in the N2O group was significantly higher compared with the O2 group at 5 minutes after opening the pleura (7 vs 5, P < 0.001, WMWodds = 7.3, 95% confidence interval (CI), 6.0 to 9.0). It was also higher in the N2O group at 10 minutes (10 vs 7, P < 0.001, WMWodds = 10.1, 95% CI, 1.9–13.3). The lung collapse scale between groups was not significant at 1 minute after opening the pleura (2 vs 2, P = 0.76, WMWodds = 1.1, 95% CI, 0.96–1.2). None of the patients developed hypoxia (SpO2 <92%) during 1-lung ventilation.
CONCLUSIONS: Filling the lung with 50% N2O before 1-lung ventilation facilitated lung collapse 5 minutes after opening the chest compared with 100% oxygen when a bronchial blocker was used. The N2O/O2 mixture (FIO2 = 0.5) did not have a harmful effect on subsequent arterial oxygenation during 1-lung ventilation.
From the *Department of Anesthesiology, Teikyo University Hospital, Tokyo, Japan; †Department of Anesthesia, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa; and ‡Graduate School of Public Health, Teikyo University, Tokyo, Japan.
Yoshimura, MD, is currently affiliated with Department of Anesthesiology, Shin-yurigaoka General Hospital, Tokyo, Japan.
Accepted for publication December 10, 2013.
Funding: The study was funded solely departmental sources.
The authors declare no conflicts of interest.
This report was previously presented, in part, at the IARS 2012.
Reprints will not be available from the authors.
Address correspondence to Kenichi Ueda, MD, 200 Hawkins Dr., 6JCPIowa City, IA. Address e-mail to firstname.lastname@example.org.
Prompt collapse of the nonventilated lung can facilitate thoracic surgery. A previous study demonstrated that as soon as ambient air can freely enter the thoracic cavity, lungs will undergo prompt partial collapse (“Phase I” lung collapse) due to their inherent elastic recoil, which occurs within 1 minute.1 When the initial prompt collapse ceases, presumably as a consequence of small airway closure, the slower second phase of lung collapse ensues, which is dependent on continuous gaseous diffusion and absorption atelectasis (“Phase II” lung collapse). Thus, efforts to promote the second phase of lung collapse would primarily occur via changing the rate of gaseous uptake in the alveoli.
Previous studies have found that the use of nitrous oxide (N2O) in the inspired gas mixture during 2-lung ventilation improves lung collapse during subsequent 1-lung ventilation with a double-lumen endotracheal tube.2,3 However, there is no study reporting the effects of N2O on lung isolation with a bronchial blocker. Therefore, we designed a prospective, randomized trial to evaluate the effectiveness of N2O for the second phase of lung collapse by using a bronchial blocker. The primary outcome of the current study was to compare the lung collapse scale at 5 minutes after opening the thorax (“Phase II” lung collapse) between the 2 groups. As a secondary outcome, the lung collapse scale was compared at 1 minute (Phase I lung collapse) and 10 minutes (late stage of Phase II lung collapse). We hypothesized that the use of N2O in the inspired gas mixture during 2-lung ventilation would lead to improvement of Phase II lung collapse during subsequent 1-lung ventilation with the bronchial blocker.
After approval of the Research Ethics Board of Teikyo University and after obtaining written informed consent, adult patients scheduled for elective thoracotomy or thoracoscopic surgery were allocated by random number assignment to one of the 2 study groups: N2O or O2. All patients had pulmonary function tests preoperatively. Patients were excluded if pleural adhesion was anticipated during preoperative assessment or if they had evidence of bullae on their chest computed tomography scans.
After placement of American Society of Anesthesiologists standard monitors, the N2O group received a gas mixture of O2 and N2O (FIO2 = 0.5), and the O2 group received 100% O2 for 3 minutes for thorough denitrogenation.3 Anesthesia was induced with propofol (1–2 mg/kg), remifentanil (0.3–0.5 μg/kg/min), and rocuronium (1 mg/kg) and was maintained with propofol infusion (120–200 μg/kg/min) and intermittent boluses of rocuronium. In the N2O group, 50% N2O was administered from induction of anesthesia to the initiation of 1-lung ventilation. The tidal volumes were 10 mL/kg ideal body weight during both 2-lung ventilation and 1-lung ventilation at the respiratory rate of 10/min without positive end-expiratory pressure. The total fresh gas flow was 2 L/min during 2-lung ventilation and 1-lung ventilation in both groups. Lung isolation was achieved with an Arndt® wire-guided bronchial blocker (Cook® Critical Care, Bloomington, IN). The patient’s trachea was first intubated with an 8.0-mm internal diameter endotracheal tube, and the bronchial blocker was then introduced into it. The fiberoptic bronchoscope (Olympus BF 3C40: Olympus Medical Systems Corp.: Tokyo, Japan; outer diameter, 3.3 mm) was inserted into the endotracheal tube along with the bronchial blocker for initial tracheobronchial surveillance. Under fiberoptic visualization, the bronchial blocker was positioned in the mainstem bronchus of the lung to be collapsed. The balloon of the bronchial blocker was inflated with 5 to 8 mL air to obtain total bronchial blockade. Once adequate initial placement was achieved, the balloon was deflated and advanced 1 cm deeper to avoid proximal dislodgement while changing the patient’s position. After the patient was turned to the lateral position, the bronchial blocker was adjusted as needed, and the balloon was inflated under direct fiberoptic visualization. The wire loop was withdrawn to convert the channel into a suction port, and 1-lung ventilation of the dependent lung was started with a FIO2 = 1.0 at the skin incision. Suction was applied with a negative pressure of 10 cm·H2O to the bronchial blocker port for 1 minute during the opening of the nondependent lung pleura.
Lung collapse was graded via video view because the operation was started with a video-assisted technique in all cases. Surgeons were blinded to the gas mixture and were instructed to assess the lung collapse scale at 1, 5, and 10 minutes after pleural opening by using a verbal rating scale from 0 (no lung deflation) up to 10 (complete collapse). If lung isolation was not satisfactory, the fiberoptic bronchoscope was inserted to diagnose and correct the problem. Baseline arterial blood gases were obtained preoperatively while patients breathed room air. After anesthetic induction, the radial artery was cannulated, and arterial blood gas samples were analyzed every 10 minutes for the first 30 minutes of 1-lung ventilation. The lowest SpO2 during 1-lung ventilation was recorded. The time required to open the nondependent lung pleura (time was measured from start of 1-lung ventilation until pleural opening) was recorded. End-tidal N2O was measured every minute from the start of 1-lung ventilation by using the anesthetic analyzer (IntelliVue G5, Phillips, Andover, MA).
Sample Size Calculation
A pilot study with 24 patients (12 patients in each group) was conducted to obtain the lung collapse scale estimate at 5 minutes for each group. The results of our preliminary study showed that the rank sum R1, for the N2O group, was 122 (P = 0.25). According to Wilcoxon rank sum test sample size calculation, a total of 42 patients (21 per group) would provide 80% power to compare the lung collapse scale at 5 minutes between groups with a 2-sided type I error rate of 0.05. Thus, 50 patients (25 per group) were planned for enrollment in the study.
All analyses were performed according to intention-to-treat. The lung collapse scale between groups was analyzed by the Mann-Whitney U test, and its odds ratio and the 95% confidence interval (CI) was expressed as WMWodds.4 Demographic data were evaluated by using Student t test for continuous variables and Fisher exact test and χ2 test for categorical variables. Statistical differences were considered to be significant if P < 0.05. SAS 9 (SAS Institute Inc. NC) was used for statistical analysis.
Fifty patients were enrolled in the study (N2O = 26, O2 = 24). All patients had satisfactory lung isolation and did not require correction of bronchial blocker malpositioning or discontinuation of 1-lung ventilation. Demographic data and other information are listed in Table 1. Data are expressed as mean ± standard deviation (SD) or median (interquartile range [IQR]) as appropriate. There were no differences between the 2 study groups with respect to preoperative pulmonary function test, type of surgery, side of surgery, or time from start of 1-lung ventilation to pleural opening. There were no differences between groups in the time interval between anesthetic induction and the initiation of 1-lung ventilation (N2O; 29 ± 3 minutes vs O2; 30 ± 3, P = 0.41). The bar graphs of the lung collapse scale, and the median lung collapse scale for each group at the different study time periods are shown in Figure 1 and Table 2. The lung collapse scale in the N2O group (median = 7, IQR = 5 to 8) was significantly higher compared with the O2 group (median = 5, IQR = 3 to 6) at 5 minutes (P < 0.001, WMWodds = 7.4, 95% CI, = 6.0–9.0) after opening the pleura, and it was still higher at 10 minutes (N2O: median = 10, IQR = 9 to 10 vs O2: median = 7, IQR = 6 to 8, P < 0.001, WMWodds = 10.1, 95% CI, 1.9–13.3). There was no difference between groups at 1 minute (N2O: median = 2, IQR = 1 to 4 vs O2: median = 2, IQR = 1 to 4, P = 0.76, WMWodds = 1.1, 95% CI, 0.96–1.2). End-tidal N2O values of the N2O group are shown in Figure 2. At the initiation of 1-lung ventilation, end-tidal N2O was close to 50%, declining progressively to approximately 10% in the first 5 minutes and hitting a plateau after 10 minutes of 1-lung ventilation. Arterial oxygenation at the different study time periods is shown in Figure 3. The O2 group had a higher PaO2 during 2-lung ventilation compared with the N2O groups. After 10 minutes of 1-lung ventilation, the O2 group may have had slightly higher PaO2 compared with the N2O group (P = 0.07). (Table 3.) There were no subsequent differences in mean PaO2 values between groups to the end of the study period. Clinically significant desaturation (SpO2 <92%) requiring alveolar recruitment maneuvers or other interventions did not occur in any subject. No patient required discontinuation of 1-lung ventilation.
The current study showed that adding N2O during 2-lung ventilation facilitated lung collapse at 5 and 10 minutes after the chest was opened (Phase II lung collapse) when a bronchial blocker was used for lung isolation. The study also demonstrated that use of N2O did not lead to greater lung collapse at 1 minute after pleural opening, consistent with the dependency of Phase I collapse on passive exhalation via the inherent elastic recoil of the lung.
Two tools are commonly used for lung isolation: the double-lumen endotracheal tube and the bronchial blocker. Although there has been a recent increase in its use, a bronchial blocker is associated with several limitations, including the need for frequent repositioning during surgery5 and slower lung collapse than with the double-lumen endotracheal tube, particularly in right-sided thoracic surgery.6–8 Based on the mechanism of lung collapse, different strategies may hasten passive venting (Phase I lung collapse) and gaseous uptake (Phase II lung collapse), the subject of the current study.
Effective lung collapse facilitates thoracic surgical procedures. However, it could be challenging in patients with chronic obstructive pulmonary disease who have decreased lung elastic recoil. To facilitate thoracoscopic surgery in patients with chronic obstructive pulmonary disease who tend to have a large amount of gas trapping, Phase II collapse plays a main role in surgical exposure because Phase I collapse does not significantly contribute to lung deflation in these patients.
Previous studies suggest that a 50% N2O/O2 inspired gas mixture during 2-lung ventilation leads to faster lung collapse during 1-lung ventilation than 100% oxygen.2,9 In theory, when ventilation to a lung unit ceases, the rate of gas uptake from that lung unit by the blood determines the rate at which absorption atelectasis develops. After initiation of 1-lung ventilation with 100% oxygen, the ongoing exhalation of N2O from the ventilated lung will increase the pressure gradient of N2O in the nonventilated lung and will result in a faster uptake of N2O in the nonventilated lung.However, if ventilation is with 100% oxygen and the nonventilated lung does not contain N2O, gaseous uptake is limited by the magnitude of the shunt and the oxygen-carrying capacity of hemoglobin.
End-tidal N2O concentrations decreased rapidly in the first 5 minutes and almost reached a plateau level by 10 minutes of 1-lung ventilation (Fig. 2). When end-tidal N2O concentrations were used to predict the concentration in a central compartment, the end-tidal N2O tracing indicated that the N2O absorbed from the dependent and nondependent lung was vented out predominantly over the 10 minutes, especially in the first 5 minutes. This is consistent with PaO2 values of the 2 groups merging beyond 10 minutes of 1-lung ventilation, suggesting that after 10 minutes of 1-lung ventilation, the arterial O2 level is determined more by the FIO2 than the prelung isolation gas mixture (Fig. 3).
Considering specific contraindication of N2O such as patients with bullae, the technique of mixing N2O needs to be used with caution. Also, there has been concern about using high concentrated N2O in general anesthesia, which potentially increases the risk of surgical wound infection or cardiac insult.10 However, those adverse effects are not consistent with some other studies and are likely from low FIO2 and long duration exposure.11,12 Therefore, the current technique, which only used 50% N2O in a short period of time, should have minimal adverse effects.
The main limitation of the current study is the method of assessing lung collapse by using the surgeons’ rating scale, which was not completely objective. However, to use a more objective assessment such as the distance of lung collapse away from the chest wall would be clinically less relevant due to the differences in sizes of the patients’ chests. Therefore, the most clinically relevant assessment of the surgical access in the hemithorax is the surgeon’s impression.13 Another limitation is the patients’ characteristics. Since all patients had normal pulmonary function tests and body mass indices, the effect might not be the same when the technique is applied to patients with poor pulmonary function tests or obesity. Further investigation is warranted for evaluating efficacy of the technique in such patients.
In summary, by using 50% N2O before 1-lung ventilation expedited Phase II lung collapse (5 to 10 minutes after the thorax is open) when a bronchial blocker was used for lung isolation. It did not affect Phase I lung collapse. This simple technique could facilitate thoracic surgery without causing hypoxia.
Name: Tatsuya Yoshimura, MD.
Contribution: This author helped design and conduct the study, analyze the data, and write the manuscript.
Attestation: Tatsuya Yoshimura has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.
Name: Kenichi Ueda, MD.
Contribution: This author helped design the study, analyze the data, and write the manuscript.
Attestation: Kenichi Ueda has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Akihito Kakinuma, MD.
Contribution: This author helped conduct the study.
Attestation: Akihito Kakinuma has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Jun Sawai, MD.
Contribution: This author helped conduct the study.
Attestation: Jun Sawai has seen the original study data and approved the final manuscript.
Name: Yoshinori Nakata, MD, MBA.
Contribution: This author helped design the study, analyze the data, and write the manuscript.
Attestation: Yoshinori Nakata has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
This manuscript was handled by: Steven L. Shafer, MD.
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