End-tidal capnographic monitoring during flexible bronchoscopy under fentanyl and midazolam sedation
Original Article

End-tidal capnographic monitoring during flexible bronchoscopy under fentanyl and midazolam sedation

Daisuke Minami1,2, Etsuko Murakami1, Yusuke Shibata1, Kayo Nakamura1, Taizo Kishino1, Nagio Takigawa3, Kiriko Onishi4, Yuki Takigawa4, Atsushi Shimonishi4, Kenichiro Kudo4, Akiko Sato4, Ken Sato4, Keiichi Fujiwara4, Takuo Shibayama4

1Department of Respiratory Medicine, Japanese Red Cross Society Himeji Hospital, Hyogo, Japan; 2Department of Respiratory Medicine, Hosoya Hospital, Okayama, Japan; 3General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan; 4Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan

Contributions: (I) Conception and design: All authors; (II) Administrative support: All authors; (III) Provision of study materials or patients: K Kudo, A Sato, K Sato, K Fujiwara, T Shibayama; (IV) Collection and assembly of data: D Minami, E Murakami; (V) Data analysis and interpretation: Y Shibata, K Nakamura, T Kishino, N Takigawa, K Onishi, Y Takigawa, A Shimonishi; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Etsuko Murakami, MD, PhD. Department of Respiratory Medicine, Japanese Red Cross Society Himeji Hospital, Hyogo, Japan; 1-12-1 Shimoteno, Himeji City, Hyogo 670-8540, Japan. Email: dm373minami@yahoo.co.jp.

Background: Bronchoscopic examination including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is well established for lung cancer diagnosis and staging. Sedation using fentanyl and midazolam is recommended during bronchoscopic examinations. Meanwhile, inadvertent oversedation is a clinical problem. The objective of this research was to estimate the frequency of apnea episodes by end-tidal capnography under fentanyl and midazolam sedation during bronchoscopy.

Methods: Eighty-five patients were enrolled retrospectively between August 2017 and March 2018 at Okayama Medical Center. Apnea was defined as the cessation of airflow for more than 10 seconds. We reviewed medical records, including capnographic data, by cap-ONE YG-227T (NIHON KOHDEN, Tokyo, Japan) during flexible bronchoscopy under fentanyl and midazolam sedation.

Results: Patients received 49.4±20.6 µg of fentanyl [mean ± standard deviation (SD)] and 4.35±2.0 mg of midazolam (mean ± SD). The patients included 52 males and 33 females; the median age was 71 (range, 31–88) years were enrolled. Apnea episodes were recorded (median duration 18 seconds) in 85 patients (100%). Prolonged apnea episodes with more than 30 seconds occurred in 56 patients (65.8%). Furthermore, the median time was 32 (range, 5–102) seconds whose delay between the onset of an apnea episode and decline in the SpO2 level of ≥4% from baseline.

Conclusions: End-tidal capnography, cap-ONE YG-227T was effective for detecting the occurrence of apnea in patients undergoing a bronchoscopic examination under fentanyl and midazolam sedation. Monitoring might be useful for preventing inadvertent oversedation.

Keywords: End-tidal capnography; bronchoscopic examination; fentanyl and midazolam sedation

Submitted Apr 24, 2021. Accepted for publication Jul 14, 2021.

doi: 10.21037/apm-21-1009

Introduction

Sedation is widely used in the USA and Europe by pulmonary physicians for bronchoscopic examinations (1-5). Bronchoscopic examination including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a useful tool for lung cancer diagnosis and staging (6-8). The American College of Chest Physicians recommends the use of benzodiazepine/opiate combination during bronchoscopy for sedation (9). British Thoracic Society guidelines in adults also recommend using these drugs for diagnostic flexible bronchoscopy (10). We showed previously, for the first time, that sedation with fentanyl and midazolam was safe and effective during bronchoscopic examinations in Japanese patients (11,12). Furthermore, we reported that sedation with fentanyl and midazolam facilitated the diagnosis of peripheral pulmonary lung cancers (13). Meanwhile, inadvertent oversedation can be a clinical problem. Forster et al. (14). reported that oversedation using midazolam and diazepam led to deep sedation and apnea episodes. Moderate sedation is necessary for safe bronchoscopy examination to prevent apnea and oxygen desaturation. End-tidal capnography monitored the occurrence of apnea episodes at a high frequency in patients during a bronchoscopic examination under midazolam sedation in a clinical setting (15,16). Here, we retrospectively revealed the occurrence of apnea episodes during bronchoscopic examinations under fentanyl and midazolam sedation by end-tidal capnography. We present the following article in accordance with the STROBE reporting checklist (available at https://dx.doi.org/10.21037/apm-21-1009).

Methods

Patient population and study design

Eighty-five patients were enrolled in this retrospective study between August 2017 and March 2018 at Okayama Medical Center. They were surely consecutive all cases who undergo bronchoscopy in the hospital. We reviewed medical records, including capnographic data, by cap-ONE YG-227T (NIHON KOHDEN, Tokyo, Japan) during flexible bronchoscopy under fentanyl and midazolam sedation. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Ethics Committee of the National Hospital Organization, Okayama Medical Center on October 25, 2017 (approval No. H29-RINKEN-ZINSOKU-65), and individual consent for this retrospective analysis was waived.

Bronchoscopy procedure

Bronchoscopic examination (one of the following: P260F, BF-260, 6C260, 1T260, P290, or UC260 Bronchovideoscope; Olympus Corp., Tokyo, Japan) was performed. All bronchoscopic procedures were performed on an inpatient basis. A total of 5 mL of 2% lidocaine was sprayed into the pharynx, and 15 mL of 2% lidocaine was administered through the channel during the procedure. Before each procedure, we sprayed 5 mL of 2% (w/v) lidocaine into the pharynx. The bronchoscope was inserted orally under conscious sedation. When fentanyl is administered with other sedatives, an initial dose of 25–50 µg is recommended with additional doses of 25 µg, as required, until the desired effect is achieved. The recommended dose of midazolam is 0.01–0.1 mg/kg (12,13). As Japanese are, on average, physically smaller than Westerners, we selected a lower dose of fentanyl.

Patient monitoring

Patients were monitored without the presence of an anesthesiologist by electrocardiography, pulse oximetry, and blood pressure monitoring every 5 min. The oxygen flow rate was increased when the SpO2 was less than 90% though a nasal cannula. It was defined as clinically significant that the SpO2 level of ≥4% from baseline decreased. The cap-ONE YG-227T monitoring device (NIHON KOHDEN) measures the concentrations of carbon dioxide in expired air continuously (Figure 1A). When the capnogram showed a flat line (Figure 1B), the clinician made sure that the sample port was not disconnected. This device was used for end-tidal capnographic monitoring (Figure 1C). The cap-ONE bite block (YG-227T; NIHON KOHDEN, Tokyo, Japan) can deliver oxygen while measuring mainstream EtCO2 during bronchoscopic procedures. In this study, apnea episodes were defined as the cessation of airflow for more than 10 seconds. We monitored the duration of the apnea episodes and the time delay between the onset of an apnea episode and a ≥4% SpO2 decline.

Figure 1 The monitoring device. (A) The monitoring device (cap-ONE YG-227T; NIHON KOHDEN, Tokyo, Japan) was used to measure the concentrations of carbon dioxide in expired air continuously. (B) The capnogram showed a flat line. (C) The monitoring device used was a cap-ONE YG-227T (NIHON KOHDEN). The red arrows indicate the concentrations of carbon dioxide.

Statistical analyses

We performed statistical analyses by Microsoft Office Excel 2010 (Microsoft Japan Corp., Tokyo, Japan). Between-group comparisons were made using unpaired Student’s t-tests. P values <0.05 were considered statistically significant.

Results

The enrolled patients included 52 males and 33 females. Their median age was 71 (range, 31–88) years. The comorbidities and diagnosis with bronchoscopy were as follows: lung cancer (n=39), infectious disease (n=19), interstitial lung disease (n=5), and other (n=22). The bronchoscopic examination used (transbronchial biopsy, bronchial brushing, bronchial washing, or EBUS-TBNA) is shown in Table 1. The baseline SpO2 level was 96.6%±1.49% (mean ± SD). The patients received 49.4±20.6 µg of fentanyl (mean ± SD) and 4.35±2.0 mg of midazolam (mean ± SD). The patients’ apnea profiles are listed in Table 2. Apnea episodes were recorded in 85 patients (100%). The number of apnea episodes per patient was 13 (range, 1–48). The duration of the apnea episodes was 18 (range, 11–161) seconds. Furthermore, the median time was 32 (range, 5–102) seconds, delayed between the onset of an apnea episode by the cap-ONE YG-227T monitoring device (NIHON KOHDEN) and decline in the SpO2 level of ≥4% from baseline. The apnea episodes for more than 30 seconds occurred in 56 patients (65.8%). As shown in Table S1, there were no significant differences in baseline SpO2 levels between the groups with and without prolonged apnea episodes lasting for more than 30 seconds. The total doses of fentanyl and midazolam were higher in the group with prolonged apnea episodes compared to the group without, although the difference was not statistically significant (fentanyl: 51.78 vs. 44.82 µg, P=0.12; midazolam: 4.34 vs. 3.96 mg, P=0.74, respectively). A representative case is shown in Figure 2; a 68-year-old man with chronic respiratory failure managed by noninvasive positive pressure ventilation had a nodule in the right lung (Figure 2A). We performed transbronchial biopsy for the nodule safely under fentanyl and midazolam sedation monitored by end-tidal capnography, while a histopathological examination revealed the presence of a squamous cell carcinoma (Figure 2B). More than 50% of the cells stained for programmed cell death ligand-1 (PD-L1).

Table 1
Table 1 Patient characteristics
Full table
Table 2
Table 2 Apnea profiles (n=85)
Full table
Figure 2 A representative case during bronchoscopy monitored by end-tidal capnography. (A) A 68-year-old man with pulmonary emphysema had a nodule in the right lung. (B) We performed a transbronchial biopsy of the nodule. The red arrow indicates endobronchial tumor.

Discussion

Inadvertent oversedation sometimes causes respiratory depression and oxygen desaturation (17), although sedation is necessary and recommended for bronchoscopic procedures (11-13). It has been published that the nadir on SpO2 decline could be delayed by 45–60 seconds after an apnea episode (18). The capnographic monitoring allows for the earlier detection of apnea episodes in patients undergoing bronchoscopic examinations under midazolam sedation, more real measurement values of carbon dioxide than pulse oximetry (15,16). In our study, cap-ONE YG-227T (NIHON KOHDEN) detected the occurrence of apnea in patients undergoing a bronchoscopic examination under fentanyl and midazolam sedation. Apnea episodes were recorded in 85 patients (100%), although clinical problems did not occur. A previous report showed that a time was 31 (range, 28–42) seconds (16), delayed between the apnea episode and SpO2 decline of ≥4%. End-tidal capnography using a cap-ONE YG-227T device (NIHON KOHDEN) revealed that the median time delay between the apnea episode and decline in the SpO2 level of ≥4% from baseline was 32 (range, 5–102) seconds. This device comprises the mainstream capnometer cap-ONE (TG-980P; NIHON KOHDEN), nasal adapter, oxygen cup, and mouthpiece. The nasal adapter collects exhaled nasal flow into a measurement cell, while the oxygen cup delivers oxygen through the patient’s nose and has a sponge to scatter oxygen for accurate CO2 monitoring (19); thus, the device was effective for detecting the occurrence of apnea. Although the difference was not statistically significant, the total doses of fentanyl and midazolam were more than in the group with prolonged apnea episodes compared to the group without. This device might be useful for preventing apnea episodes and oversedation.

During bronchoscopy, oxygen desaturation occurs at a higher frequency than during other examinations (e.g., esophagogastroduodenoscopy and colonoscopy) (20-22). Pulse oximetry has become the standard of care in endoscopy units around the world. However, pulse oximetry may not adequately reflect hypoventilation, apnea, impending hemodynamic instability, or vasoconstrictive shock. Capnography has emerged as a noninvasive way of measuring patient ventilation that may be especially useful in patients with comorbidities of lung disease during gastrointestinal endoscopy. It is necessary for safe procedural sedation to detect hypoventilation as early as possible (23,24). In the present study, we performed transbronchial biopsy safely on a patient with lung squamous cell carcinoma with chronic respiratory failure monitored by end-tidal capnography (Figure 2), and more than 50% of the cells stained for PD-L1. Lung cancer is the leading cause of cancer-related mortality worldwide (25). Approximately 85% of cases are non-small cell lung cancer (NSCLC), and tissue analysis is key in the treatment of NSCLC (26,27). Many molecule inhibitors induce rapid and deep responses and confer superior disease control compared with standard platinum doublet chemotherapy (28-31). Indications of capnography for advanced lung cancer patients during endoscopic procedures might be of interest. This study has one limitation. We did not see assessment of all subjects with Richmond Agitation-Sedation Scale. This relatively high midazolam and fentanyl doses might be considered as apnea risk factors.

In previous report, sedation depth was analyzed to reveal noninvasive mechanical ventilation—flexible bronchoscopy risk factor (32). It is necessary to be careful for overdose sedation which could cause severe respiratory depression and oxygen desaturation. The other limitation of our study is that it was a small retrospective analysis. A large-scale study based on clinical practice is needed to confirm these findings.

Acknowledgments

We thank Dr. Sho Mitsumune, Dr. Tadahiro Kuribayashi, and Mr. Fumihiko Takatori for performing the bronchoscopic examinations and for helpful discussions. And the English in this document has been checked by at least two professional editors, both native speakers of English. For a certificate, please see: http://www.textcheck.com/certificate/2zRVbm

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://dx.doi.org/10.21037/apm-21-1009

Data Sharing Statement: Available at https://dx.doi.org/10.21037/apm-21-1009

Peer Review File: Available at https://dx.doi.org/10.21037/apm-21-1009

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/apm-21-1009). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Ethics Committee of the National Hospital Organization, Okayama Medical Center on October 25, 2017 (approval No. H29-RINKEN-ZINSOKU-65), and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: Minami D, Murakami E, Shibata Y, Nakamura K, Kishino T, Takigawa N, Onishi K, Takigawa Y, Shimonishi A, Kudo K, Sato A, Sato K, Fujiwara K, Shibayama T. End-tidal capnographic monitoring during flexible bronchoscopy under fentanyl and midazolam sedation. Ann Palliat Med 2021;10(8):8665-8671. doi: 10.21037/apm-21-1009

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