Sustained breath-holds in bronchoscopy: a pause worth taking?—a narrative review

Introduction

The diagnosis of lung cancer in patients with peripheral pulmonary lesions (PPLs) has undergone a remarkable transformation in the past decade (1). Innovations such as electromagnetic navigation (EMN) and robotic bronchoscopy have significantly enhanced our ability to access and biopsy lesions previously considered unreachable. Despite these technological advances, diagnostic yield (DY) remains highly variable (2,3).

In the United States (US), advanced diagnostic bronchoscopy using EMN or robotic platforms is typically performed under general anesthesia with neuromuscular blockade in procedural suites or operating rooms, in accordance with manufacturer recommendations (4-6). This controlled setting enables precise management of ventilation and supports the use of advanced imaging modalities, such as intraprocedural cone-beam computed tomography (CBCT) and digital tomosynthesis (DT). As bronchoscopists are increasingly asked to sample smaller and more mobile lesions, respiratory motion becomes a key contributor to the phenomenon of computed tomography (CT)-to-body divergence—a mismatch between static pre-procedural CT and the dynamic real-time anatomy encountered during bronchoscopy (7).

Multiple strategies have been explored to reduce CT-to-body divergence, including ventilatory techniques to minimize respiratory motion and atelectasis. Among these, the breath-hold (BH) maneuver has attracted growing interest in the US (8,9). During a BH maneuver, mechanical ventilation is suspended while maintaining a continuous flow of oxygen delivery and a set airway pressure. Brief BH maneuvers are necessary to obtain quality intraprocedural 3D images, typically requiring only 30–60 seconds. More recently, to suppress respiratory motion during the target biopsy, some operators have employed sustained BH maneuvers, reporting the feasibility of maintaining them safely for extended durations.

The theoretical benefits of sustained BH maneuvers in advanced bronchoscopy are compelling. By eliminating respiratory motion, these maneuvers may improve diagnostic and therapeutic precision, particularly when targeting small lesions prone to displacement. However, the physiological consequences of prolonged apnea, especially in patients with underlying cardiopulmonary conditions, are not fully understood. Furthermore, while anecdotal evidence supports the utility of this technique, robust clinical data are lacking. Moreover, there is a significant gap in the literature regarding systematic guidance on patient selection, contraindications, and the implementation of best practices to use this maneuver safely.

Considering the limited data specific to bronchoscopy, this narrative review and commentary adopts a conceptual approach that draws on foundational physiology and analogous procedural fields to explore the potential role of sustained BH maneuvers in modern robotic and EMN bronchoscopy as performed in the US under general anesthesia. By synthesizing insights from adjacent surgical disciplines, we identify critical knowledge gaps, examine emerging bronchoscopic applications, and outline a structured research agenda to support future investigations and the safe clinical integration of these maneuvers. We present this article in accordance with the Narrative Review reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1112/rc).

Methods

The first author (A.P.R.) conducted a comprehensive review of the literature using Ovid MEDLINE, PubMed, EMBASE, and Google Scholar, covering all available records from the date of database inception through 1st May 2025. The search included studies published in English and utilized the Medical Subject Headings (MeSH) terms and relevant text words: “apneic oxygenation”, “physiology of apneic oxygenation”, “permissive hypercapnia”, “breath-hold techniques”, “breath-holds in surgery”, “apneic oxygenation in surgery”, and “ventilation strategies in bronchoscopy”. Only complete manuscripts were included for consideration. Articles were selected based on relevance, including those of interest cited by the initially identified articles. The search strategy is detailed in Table 1.

Historical perspective

The concept of apneic oxygenation has historical roots that span several centuries. One of the earliest documented instances dates to 1666, when polymath Robert Hooke observed that canines could maintain cardiac function with a continuous air supply via bellows, even without diaphragmatic or thoracic movement (10). Nearly three centuries later, Meltzer built upon this observation (11), demonstrating that animals could sustain life for over four hours with continuous lung inflation despite the absence of what he called “normal or artificial rhythmic respiratory movements”.

Frumin and colleagues conducted the first rigorous clinical investigation involving humans in 1959 (12). Their study, which involved eight healthy subjects undergoing minor surgical procedures, aimed to investigate diffusion respiration in humans. The study showed that seven participants tolerated apnea durations exceeding 30 minutes, with times ranging from 18 to 55 minutes. The study documented significant hypercapnia (peak PaCO₂ reaching 250 mmHg) and acidemia (lowest recorded pH of 6.72), yet only minor intraoperative complications were observed. Two patients developed arrhythmias requiring apnea discontinuation: one with a premature ventricular contraction that developed after 55 minutes of apnea, and the other a brief episode of ventricular tachycardia, both of which resolved spontaneously following resumption of ventilation.

In a subsequent investigation, Fraioli and colleagues examined apneic oxygenation in two distinct surgical populations (13). The first group (n=18) underwent laryngoscopy with continuous oxygen flow by nasal cannula (6 L/min), while the second group (n=13) received continuous inflow of 100% fraction of inspired oxygen (FiO₂) through cuffed endotracheal tubes during minor surgical procedures. All patients in the first group tolerated apnea for approximately 15 minutes without desaturation or hemodynamic instability. In contrast, nine patients (50%) in the second group could not sustain apnea beyond 5 minutes. Further analysis revealed that patients in the second group had higher baseline body mass indices and reduced functional residual capacities, suggesting that limited physiological reserve may impair tolerance to sustained apnea.

These pioneering studies and others (14,15) significantly advanced our understanding of respiratory physiology by demonstrating that tissue oxygenation can be maintained for sustained periods without mechanical ventilation. However, these studies primarily involved healthy individuals or those undergoing minor procedures, whereas patients undergoing bronchoscopy often have significant cardiopulmonary comorbidities. These differences and advancements in monitoring underscore the need for a deeper understanding of the physiological mechanisms behind apneic oxygenation before their widespread adoption in advanced diagnostic bronchoscopy.

The physiology of apneic oxygenation

To understand the feasibility of sustained BH maneuvers in bronchoscopy, it is essential to first review the underlying physiology that enables oxygenation in the absence of ventilation.

The physiological mechanisms behind apneic oxygenation are complex but well-established. Early research demonstrated that oxygen continues to diffuse into pulmonary tissues during sustained periods of apnea, provided the conducting airways contain a sufficient and continuous oxygen reservoir (16,17). This phenomenon occurs due to the favorable partial pressure gradient that drives oxygen from the alveoli into the bloodstream. While carbon dioxide diffuses more rapidly because of its higher solubility in tissue, the strong oxygen gradient, rather than active breathing, sustains oxygen delivery during apnea.

Although the solubility of oxygen in blood is relatively low, the partial pressure in the alveoli at room air (approximately 104 mmHg) is significantly higher than that in deoxygenated capillary blood (around 40 mmHg) (18). This steep gradient enables effective diffusion across the alveolar membrane (Figure 1). Importantly, this gradient is maintained by several factors, including low alveolar levels of carbon dioxide and nitrogen, and the rapid binding of oxygen to hemoglobin, which keeps the partial pressure of oxygen in the blood low. These physiological dynamics work together to support continued oxygen uptake, even in the absence of ventilation.

Figure 1 Oxygen diffuses from the alveoli into the pulmonary capillaries due to the higher partial pressure of oxygen in the alveoli compared to the blood. This pressure gradient drives oxygen across the respiratory membrane into the blood, where it binds to hemoglobin in red blood cells for transport. At the same time, CO₂, primarily transported in the blood as bicarbonate (HCO₃⁻), is converted back into CO₂ within red blood cells by the enzyme carbonic anhydrase. This CO₂ then diffuses into the alveoli to be exhaled. Source: Adapted from OpenStax Anatomy & Physiology, 2020 (access for free at https://openstax.org/books/anatomy-and-physiology-2e/pages/1-introduction), used under the terms of Creative Commons Attribution 4.0 International License. (© Rice University, CC BY 4.0).

While the diffusion-driven mechanism is considered the primary factor in sustaining oxygenation, other potential contributors have been proposed. One such factor is cardiogenic oscillations, which result from pressure changes in the airways due to cardiac movement. Theoretically, these oscillations could assist in the compression and expansion of the conducting airways, aiding in the delivery of oxygen and the clearance of CO₂; however, their contribution is likely minimal compared to the primary diffusion-driven theory outlined above. Other proposed mechanisms include thoracic or diaphragmatic movements, which may generate small amounts of bulk flow that support gas exchange (19).

Although oxygenation can be sustained during prolonged apnea due to a favorable pressure gradient, the accumulation of CO₂ presents significant challenges. Contrary to earlier assumptions, the rise in CO₂ is non-linear, as described by Eger and Severinghaus in 1961 and reproduced in multiple subsequent studies (20,21). Initially, the rate of CO₂ accumulation is rapid, with an increase of approximately 13.4 mmHg within the first minute of apnea, followed by a more gradual rise of about 3.0 mmHg per minute. This pattern was further confirmed by Stock and colleagues (21), who observed a 12 mmHg increase in the first minute, followed by a more gradual rise of 3.4 mmHg per minute thereafter. These findings suggest that, although the exact mechanisms remain unclear, the rate of CO₂ accumulation may slow as the duration of apnea increases.

The severity of hypercapnia has been shown to produce distinct effects on hemodynamics. Mild hypercapnia can activate the sympathoadrenal axis, which may elevate mean arterial pressure (22,23). However, as hypercapnia becomes more pronounced, it can lead to significant hemodynamic instability, including life-threatening arrhythmias, hypotension, and even death (24,25). These risks highlight the need to continuously monitor CO₂ levels to ensure levels do not exceed safe thresholds. Blood gas analysis and non-invasive end-tidal carbon dioxide (ETCO₂) measurement are commonly used. However, it is essential to recognize that the gap between ETCO₂ and PaCO₂ can widen with sustained apnea, leading to inaccurate assessments of PaCO₂ when relying solely on ETCO₂ (26).

The pathophysiological consequences of acute hypercapnia are controversial, with studies showing both harmful and protective effects depending on the context. In acute respiratory distress syndrome, permissive hypercapnia has been associated with reduced ventilator-induced lung injury and improved clinical outcomes (22,27,28). These benefits may arise from immunomodulatory effects (29), reduced oxidative stress (30), and improved lung mechanics, which may involve the inhibition of nuclear factor-κB (NF-κB) signaling (31,32). However, these findings are derived from lung-protective ventilation strategies and may not directly translate to the setting of sustained apnea during bronchoscopy, particularly in patients with baseline hypercapnia.

Apneic oxygenation in modern surgery

Insights from adjacent surgical disciplines, particularly laryngotracheal surgery (33-35), offer a valuable clinical precedent for the use of apneic oxygenation techniques. These procedures are often performed using suspension laryngoscopy without the use of endotracheal tubes to maximize surgical exposure. As a result, apneic oxygenation is frequently employed to maintain oxygenation while preserving an unobstructed view of the airway.

A multicenter retrospective study by Rutt et al. evaluated apneic oxygenation in patients undergoing laryngotracheal procedures (33). High-flow nasal oxygen (55–70 L/min) was delivered via an Optiflow™ (Fisher & Paykel, Auckland, New Zealand) system, providing humidified 100% oxygen during spontaneous respiration and throughout the ensuing apneic period. The mean total apneic time was 23.9 minutes (range, 13–40 minutes). Among 38 adults undergoing glottic incision, 55.3% (21 patients) completed the procedure without requiring an alternative airway. However, 34.2% (13 patients) experienced oxygen desaturation (SpO₂ <88%), prompting intubation, and 10.5% (4 patients) required jet ventilation. Notably, in over half of the desaturation cases, laser or thermal ablation limited the FiO₂ used, likely contributing to hypoxemia.

A prospective randomized trial compared pre-hyperventilation plus pre-oxygenation to pre-oxygenation alone in patients undergoing microlaryngeal surgery (36). The hypothesis was that reducing baseline PaCO₂ through hyperventilation could prolong the “safe apnea” duration. The study found a mean apnea time of 22.5±4.5 minutes without significant desaturation. Arterial CO₂ rose non-linearly during apnea, initially increasing then plateauing, with an average rise of 1.8±0.4 mmHg/min. End-tidal CO₂ increased by 0.9±0.3 mmHg/min, while pH dropped from 7.44±0.04 to 7.14±0.01. However, hyperventilation did not significantly alter PaCO₂ levels at five minutes or extend the apneic window compared to normoventilation.

Low-flow oxygen delivery has also been investigated as a strategy for sustaining oxygenation during apnea (37). In a prospective observational study, 64 patients undergoing microlaryngoscopy under general anesthesia received low-flow oxygenation at 0.5–1.0 L/min. The mean apnea duration was 18.7±7.2 minutes, and 96.9% (62 out of 64) of patients completed the procedure without the need for mechanical ventilation. Despite a gradual increase in venous CO₂ (0.15±0.10 kPa/min), oxygen saturation remained stable throughout, and no adverse events were reported.

Beyond laryngoscopic procedures, apneic oxygenation has been utilized in other specialized surgical contexts. These include one-lung ventilation during thoracic procedures (38), complex tracheal surgery (39,40), rigid bronchoscopy (41), and internal mammary artery harvesting (42) in patients undergoing coronary artery bypass grafting. Despite these well-established applications, the use of apneic oxygenation in advanced diagnostic bronchoscopy remains a novel and emerging practice.

Apneic oxygenation in bronchoscopy

Although rooted in surgical precedent, the application of apneic oxygenation in bronchoscopy remains nascent. In this section, we examine its current use and evolving evidence base. Several recent studies have explored motion mitigation strategies, underscoring the growing recognition of respiratory control as a critical determinant of procedural success in diagnostic bronchoscopy. Notably, the ventilatory strategy to prevent atelectasis during bronchoscopy (VESPA) randomized controlled trial (8) demonstrated that a ventilatory approach incorporating lung recruitment, FiO₂ titration (<100%), and positive end-expiratory pressure (PEEP) of 8–10 cmH₂O significantly reduced atelectasis without increasing complications. Additionally, expert consensus statements from international societies (43) now explicitly recommend optimized anesthesia protocols to minimize atelectasis and respiratory motion during CBCT-guided robotic-assisted bronchoscopy.

The lung navigation ventilation protocol (LNVP) developed by Bhadra and colleagues (9) is the only published approach that explicitly describes tissue sampling under apneic conditions following advanced imaging. The authors’ workflow involved performing an eight-second CBCT sweep while patients were held at a stable PEEP using the adjustable pressure-limiting valve on the anesthesia machine. To maintain alignment between the CT overlay and actual anatomy, biopsies were performed at the same airway pressure. Ventilation was resumed for at least 30 seconds every 4 to 6 minutes, with continuous ETCO₂ monitoring throughout. High oxygen flow rates, up to 15 L/min, were used to support oxygenation for the duration of the hold.

Nevertheless, despite minimal evidence regarding safety, tolerability, or impact on DY, these techniques are gaining traction within the bronchoscopy community. This raises important questions about whether such maneuvers should be performed outside of research settings. Concerns exist regarding extended hypercapnia in vulnerable populations, including patients with chronic respiratory failure, chronic obstructive pulmonary disease, intracranial pathology, and pulmonary hypertension, among others. Significant knowledge gaps persist regarding appropriate patient selection, optimal ventilator settings, safe duration limits, and potential improvements in DY and accuracy.

Based on the reviewed literature, we can reasonably hypothesize that sustained apneic oxygenation may be well-tolerated during bronchoscopy, analogous to other surgical procedures. The physiological principles supporting its use are well-established. However, it is essential to note that current evidence primarily addresses acute complications during the procedure and the immediate postoperative period. The potential long-term consequences of prolonged apnea, such as cognitive impairment or other sequelae, remain largely unexplored, particularly in elderly patients or those with significant cardiopulmonary comorbidities. Additionally, using maximal FiO₂ to prolong safe apnea challenges conventional concerns regarding absorption atelectasis, underscoring the need for careful patient selection and monitoring.

While existing studies support the feasibility of sustained apneic oxygenation, they also expose key knowledge gaps that must be addressed before routine adoption in practice (Table 2). These include limited safety data in patients with cardiopulmonary comorbidities, unclear guidance on optimal apnea duration and patient selection, and a lack of standardized technical parameters such as oxygen flow rates and monitoring strategies. Additionally, clinical efficacy and long-term outcomes remain unproven, and no comparative studies evaluate this approach against alternative techniques. The absence of evidence-based protocols further hinders consistent adoption across diverse clinical settings. A summary of the proposed clinical benefits, physiologic risks, and current limitations is provided in Table 3. Robust, well-designed research studies are urgently needed to close these gaps and guide safe, effective implementation.

Future research directions

Addressing the knowledge gaps surrounding sustained apneic oxygenation in bronchoscopy will require a focused, multidisciplinary research effort that integrates physiologic understanding with clinical practicality. Initial studies should focus on understanding the physiologic tolerance to prolonged apnea across diverse patient populations, particularly those with cardiopulmonary comorbidities. By gradually increasing apnea duration under controlled conditions, we can begin to define safe upper limits, identify early warning signs of intolerance, and clarify the physiologic trade-offs involved in maintaining oxygenation while permitting transient hypercapnia.

Crucially, these studies should incorporate comprehensive monitoring parameters. Continuous pulse oximetry and capnography are essential, but serial blood gas analyses must supplement them to track PaO₂, PaCO₂, and pH changes throughout the procedure and recovery. Hemodynamic surveillance—including invasive or noninvasive blood pressure monitoring, heart rate variability, telemetry, and vasopressor requirements will help define cardiovascular tolerance to sustained hypercapnia and acidemia. Neurological assessments, both intra-procedural (e.g., level of consciousness in sedated patients) and post-procedural (e.g., cognitive recovery scores, delirium screening), will be critical for ruling out occult sequelae of transient hypercapnia.

With physiologic feasibility established, the next step is refining optimal patient selection for the maneuver. Patients are not likely to tolerate prolonged apnea equally, making it essential to identify those most likely to benefit and those at higher risk. Stratification tools incorporating pulmonary function tests, echocardiography, gas exchange profiles, and relevant comorbidities will be key. Procedural variables also need to be studied. Which oxygenation methods and flow rates best maintain oxygenation while minimizing absorption atelectasis? Which physiologic thresholds should prompt early BH termination? Can an optimal PEEP extend safe apnea time? Lastly, the effects of anesthetics, analgesics, and vasopressors must be understood to optimize ventilation-perfusion matching and CO₂ clearance.

Meaningful evaluation of sustained apneic oxygenation in bronchoscopy can only proceed once its physiologic and safety foundations are rigorously established. Given the complexity of procedural interventions, a structured approach to evidence generation is essential. The IDEAL (Idea, Development, Assessment, Long-Term Assessment) framework provides a potential roadmap to guide this process, beginning with early development studies and advancing toward robust comparative trials (43) (Table 4). These studies should consider patient outcomes, proceduralist satisfaction, and differences across patient subgroups. Ultimately, for this technique to move from concept to routine use, it must be proven effective, safe, and scalable across diverse practice settings through collaboration between pulmonologists, anesthesiologists, surgeons, and physiologists.

Conclusions

Sustained BH maneuvers may offer a promising solution to the ongoing challenge of CT-to-body divergence in advanced diagnostic bronchoscopy. Insights from other surgical fields suggest prolonged apneic oxygenation is feasible when paired with appropriate techniques and vigilant monitoring. However, current evidence specific to bronchoscopy is insufficient to inform routine use, with critical evidence gaps in safety data and clinical efficacy. In the interim, clinicians should adopt a cautious approach, prioritizing patient safety, implementing robust physiologic monitoring, and carefully selecting candidates. With thoughtful investigation and responsible clinical integration, sustained BH maneuvers may significantly enhance target lesion precision, but their promise must first be studied through high-quality evidence.

Acknowledgments

The authors appreciate support from the Vanderbilt Interventional Pulmonary Research (VIPR) Lab.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1112/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1112/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1112/coif). J.D.D. provides consulting and proctoring services for Intuitive. R.P. provided one time consulting for Noah in 2022. R.J.L. has received consulting fees, speaking honoraria, and travel support related to speaking engagements from Intuitive. K.B. serves as a consultant for Noah Medical. F.M. has received research grants from Medtronic and Erbe, and consulting fees from Medtronic, Johnson & Johnson (J&J) and Intuitive. The other 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.

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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