Bronchoscopy Without Sedation in Healthy Volunteers

Diagnostic bronchoscopy is a cornerstone of pulmonary medicine, but can be induce anxiety for patients. Patient discomfort and coughing can lead to suboptimal bronchoscope wedging and can compromise diagnostic yield. The British Thoracic Society (grade B) 1Du Rand I. A. Blaikley J. Booton R. et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013; 68: i1-i44Crossref PubMed Scopus (609) Google Scholar and the American College of Chest Physicians2Wahidi M. M. Jain P. Jantz M. et al. American College of Chest Physicians consensus statement on the use of topical anesthesia, analgesia, and sedation during flexible bronchoscopy in adult patients. Chest. 2011; 140: 1342-1350Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar recommend titration of IV moderate sedation to comfort, but this carries a range of potential adverse events, including respiratory depression, hypotension, and vomiting. In contrast, topical anesthesia offers a shorter duration of action and a wider therapeutic index. 3Matot I. Kramer M. R. Sedation in outpatient bronchoscopy. Respir Med. 2000; 94: 1145-1153Abstract Full Text PDF PubMed Scopus (51) Google Scholar Although upper airway endoscopy is performed commonly without sedation, the tolerability of sampling the lower airways without sedation has not been studied systematically. Based on prior small studies of unsedated bronchoscopy in healthy volunteers, 4Morris L. G. Zeitler D. M. Amin M. R. Unsedated flexible fiberoptic bronchoscopy in the resident clinic: technique and patient satisfaction. Laryngoscope. 2007; 117: 1159-1162Crossref PubMed Scopus (21) Google Scholar we designed this prospective study to optimize airway topical anesthesia using lidocaine solution delivered via a high-efficiency nebulizer, atomizer, and bronchoscope as well as jelly via lollypop and bronchoscope. Our aim was to describe the protocol for unsedated research bronchoscopy using solely topical lidocaine and to report the safety and efficacy of BAL in collecting human alveolar macrophages (HAMs). Before conducting the study, unsedated bronchoscopy was performed on one investigator (J. I. P. ; age, 68 years) to assess safety. The investigator reported a discomfort level of "1 to 2 out of 5, " and serum lidocaine was 2. 2 μg/mL at the end of the procedure and undetectable 30 min later (toxic serum level, > 5 μg/mL). During protocol optimization before the study, we found that 4% nebulized lidocaine provided significantly better anesthesia to the lower airways than 2% solution. Eligible volunteers were between 18 and 50 years of age without medical comorbidities and in good health. All participants underwent a medical history interview, physical examination, serum chemistry analysis, spirometry, and exhaled CO2 testing. Bronchoscopy was conducted at the Barter Clinical Research Unit (South Texas Veterans Health Care System and University of Texas Health at San Antonio) under the supervision of the University of Texas Health at San Antonio Institutional Review Board (Identifier: HSC20170667H). Total lidocaine dose was 2. 65 mg/kg (minimum toxic dose, 6. 4 mg/kg). Topical anesthesia was achieved through sequential nebulized, oral, atomized, and bronchoscopic administration of lidocaine (Fig 1). Bronchoscopy was performed by an experienced pulmonologist using the Olympus BF-P60 bronchoscope (diameter, 4. 9 mm) with a nasal approach. BAL was performed in the right middle lobe. After bronchoscopy, the participants were observed for 2 h and did not eat until numbness had resolved. Telephone follow-up was conducted the following day to assess complications and discomfort level (1 = no discomfort, 5 = very uncomfortable). BAL samples were transported on ice, centrifuged, and washed twice at 4° C within 6 h, and the pellet was resuspended in RPMI 1640 with penicillin G (10, 000 U/mL). BAL cells were counted on a hemocytometer and 5 × 104 cells were transferred to cytoslides. The cytoslides were dried, stained using HEMA 3 (Fisher Health Care), washed with water, dried, and examined with an AE2000 microscope (Motic). The study volunteers (n = 25) were young (mean age, 27. 4 years; range, 18-36 years) with equal sex distribution (48% female) and normal spirometry values: FEV1, 98% (range, 76%-115%) ; FEV1 to FVC ratio, 0. 98 (range, 0. 89-1. 10). No active smokers were included as confirmed by exhaled carbon monoxide of 95% throughout. Two participants experienced transient desaturation to 88% to 89% oxygen saturation and recovered spontaneously without supplemental oxygen. One participant who reported 4 of 10 discomfort also experienced desaturation to 87% when coughing after the procedure. No changes from baseline were noted for BP or heart rate before or after the procedure. Table 1Bronchoscopy With Topical AnesthesiaDetailsDataDuration, min7 (4-10) Discomforta1 = no discomfort to 5 = very uncomfortable. 2. 3 (1-4) Oxygenation Desaturation < 89%2 (8) Lowest SpO2, %96 (87-100) Discharge SpO2, %97 (88-100) Procedure details Bronchoscopic lidocaine, mL8 (6-12) BAL return, mL84 (45-110) BAL return, % instilled56 (30-73) HAM yield, 106 cells/mL4. 5 (1. 2-8. 6) Cytospin confirmation, %bn = 20. 89 (75-98) Mucoid BAL return5 (20) Blood-tinged returncContaminated from nasal turbinate trauma. 1 (6) Data are presented as No. (%) or mean (range). SpO2 = oxygen saturation. a 1 = no discomfort to 5 = very uncomfortable. b n = 20. c Contaminated from nasal turbinate trauma. Open table in a new tab Data are presented as No. (%) or mean (range). SpO2 = oxygen saturation. Although 26% of BAL samples exhibited blood-mixed fluid or mucus, this did not have a detrimental impact on the yield of HAMs, which was satisfactory (mean, 4. 5 × 106 cells/mL). Cytospin analysis revealed that the mean percentage of macrophages in the BAL samples was 89% (range, 75%-98%). In this study involving healthy volunteers, bronchoscopy without sedation or supplemental oxygen using multimodal topical lidocaine was well tolerated and proved to be a viable method for isolating HAMs. No procedures were terminated prematurely, and no severe discomfort was reported. The yield of HAMs was comparable with that of other studies involving healthy volunteers5Heron M. Grutters J. C. ten Dam-Molenkamp K. M. et al. Bronchoalveolar lavage cell pattern from healthy human lung. Clin Exp Immunol. 2012; 167: 523-531Crossref PubMed Scopus (72) Google Scholar and was acceptable for ex vivo studies. 6Pahari S. Arnett E. Simper J. et al. A new tractable method for generating human alveolar macrophage-like cells in vitro to study lung inflammatory processes and diseases. mBio. 2023; 14e0083423PubMed Google Scholar The facility fee of the procedure (1, 598 from Medicare) was eliminated, making this a very cost-effective protocol. Our protocol was designed to anesthetize the airway comprehensively with sequential lidocaine via nebulizer, atomizer, lollipop, and bronchoscope while ensuring a less than toxic lidocaine limit of 5 to 7 mg/kg. 7Milman N. Laub M. Munch E. P. et al. Serum concentrations of lignocaine and its metabolite monoethylglycinexylidide during fibre-optic bronchoscopy in local anaesthesia. Respir Med. 1998; 92: 40-43Abstract Full Text PDF PubMed Scopus (34) Google Scholar Most participants in our study achieved adequate anesthesia and did not experience significant coughing. However, the two self-limiting desaturation events were associated with coughing, suggesting suboptimal anesthesia in those patients. Although supplemental oxygen is routine in most bronchoscopy protocols, the omission of supplemental oxygen did not result in serious adverse events. Previous studies with patients with asthma reported no adverse events with higher doses of lidocaine (up to 8. 2 mg/kg). Given that our study used lidocaine doses well below this threshold, future investigations could consider additional lidocaine to the turbinates and oropharyngeal 10% lidocaine spray, which may be more effective than nebulized lidocaine. 8Dhooria S. Chaudhary S. Ram B. et al. A randomized trial of nebulized lignocaine, lignocaine spray, or their combination for topical anesthesia during diagnostic flexible bronchoscopy. Chest. 2020; 157: 198-204Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 9Madan K. Biswal S. K. Tiwari P. et al. Nebulized lignocaine for topical anaesthesia in no-sedation bronchoscopy (NEBULA): a randomized, double blind, placebo-controlled trial. Lung India. 2019; 36: 288-294Crossref PubMed Scopus (14) Google Scholar The optimal topical anesthesia protocol remains unknown and requires further study with comparison of delivery mechanisms. Future studies also may consider using thinner bronchoscopes to maximize patient comfort. Our study has several limitations. First, we did not assess the adequacy of topical anesthesia before advancing the bronchoscope, which might have mitigated the single episode of moderate discomfort. Second, we did not evaluate operator comfort and satisfaction, which may be affected adversely compared with sedation-based approaches. Third, this study did not investigate patients with pulmonary disease, which will require further studies with more intensive intraprocedural monitoring. Finally, the nature of minor cell populations obtained was not investigated fully in this study and will be characterized further in subsequent studies. In conclusion, this pilot study supports the feasibility and further investigation of research bronchoscopy without sedation. By minimizing the need for sedation, this approach has the potential to improve patient safety, to enhance procedural tolerability, and to facilitate research bronchoscopy. Funding provided by the Bill & Melinda Gates Foundation and the National Institutes of Health Grants NIA P01 AG051428 and NIAID 1R01AI136831-01A1.