Highlights
- The multicentre PROTECT study demonstrates that routine prophylactic use of adrenaline or ice-cold saline does not significantly reduce iatrogenic bleeding in unselected patients undergoing endobronchial biopsy.
- Subgroup analysis suggests a potential benefit of ice-cold saline in patients younger than 65 years (RR 0.90, p=0.04), warranting further targeted investigation.
- Evidence-based practice is shifting away from routine pre-procedural pathology (coagulation and platelets) for low-risk patients, favoring a targeted approach based on clinical risk factors.
- Technological advancements, including robotic-assisted bronchoscopy and cryoprobe biopsies, offer superior diagnostic yields compared to conventional methods while maintaining favorable safety profiles.
Background
Endobronchial biopsy (EBB) is a fundamental diagnostic procedure in interventional pulmonology, utilized for the evaluation of endobronchial lesions, sarcoidosis, and other central airway pathologies. Despite its high diagnostic utility, iatrogenic bleeding remains a dreaded complication. While most bleeding events are mild and self-limiting, catastrophic haemorrhage can occur, potentially leading to airway obstruction, asphyxiation, and death. Historically, various haemostatic agents—most commonly adrenaline and ice-cold saline—have been used prophylactically based on physiological principles of vasoconstriction and thermal-induced vascular contraction. However, clinical evidence supporting this routine practice has been surprisingly sparse. The PROTECT study (Prophylactic haemostatic treatment to control iatrogenic bleeding during endobronchial biopsy) was designed to address this evidence gap in a robust, multicentre, randomized controlled environment.
Key Content
The PROTECT Study: Randomized Evidence for Prophylactic Haemostasis
The PROTECT trial represents a significant milestone in interventional pulmonology research. In this multicentre, single-blind, placebo-controlled study, 462 participants were randomized to receive either adrenaline, ice-cold saline, or a normal saline placebo prior to EBB. The study’s primary outcomes were the Bleeding Severity Scale (BSS) and the Visual Analogue Scale (VAS) scores at the termination of the biopsy.
The results revealed that prophylactic haemostasis did not statistically improve bleeding outcomes across the entire study population. This finding challenges the conventional wisdom and routine clinical practice in many centers that apply these agents universally. Notably, both adrenaline and ice-cold saline were found to be safe, with no significant increase in adverse events. However, a glimmer of efficacy was observed in patients under 65 years old, where ice-cold saline showed a trend toward reduced bleeding (RR 0.90 [95% CI 0.82-0.99], p=0.04). This suggests that while universal prophylaxis may be unnecessary, age-related vascular changes might influence the efficacy of thermal haemostasis.
Risk Assessment and Pre-procedural Optimization
A critical component of avoiding bleeding complications is the identification of high-risk patients. Recent data from a retrospective review of 436 bronchoscopic procedures (PMID: 41549992) indicates that routine pathology testing (hemoglobin, platelets, and coagulation) prior to bronchoscopy has limited clinical impact in patients without established risk factors. Only 4% of tests led to clinical interventions, all of which were in patients with known risk factors. This supports a shift toward a more sustainable, targeted screening model, which reduces unnecessary healthcare costs (estimated at ~20,000 USD per 436 procedures) and environmental impact without compromising patient safety.
Comparative Safety of Bronchoscopic Access Approaches
When selecting the biopsy method, clinicians must weigh diagnostic yield against complication risks. A meta-analysis comparing endobronchial, transthoracic, and endovascular access for lung fiducial marker insertion (PMID: 41738525) highlighted that endobronchial access is associated with significantly lower rates of hemoptysis and pneumothorax compared to transthoracic approaches. Similarly, real-world analyses of middle lung zone lesions (PMID: 41718096) confirm that transbronchial approaches lead to fewer complications and shorter workup durations, even when advanced technologies like navigation or robotics are unavailable.
Technique-Driven Yield and Safety
The evolution of biopsy tools also plays a role in safety. Robotic-assisted bronchoscopy, particularly when paired with cryoprobe biopsies, has shown superior histopathologic yield compared to conventional forceps (PMID: 41718084). Cryobiopsy allows for larger, more intact tissue samples, which can often be obtained with fewer passes. In the context of the PROTECT study, optimizing the number of passes—ideally plateauing at three as suggested by recent data—may be as important for bleeding control as the use of prophylactic agents.
Expert Commentary
The PROTECT trial provides a necessary reality check for interventionalists. The lack of overall benefit for prophylactic adrenaline and ice-cold saline suggests that the lung’s intrinsic haemostatic mechanisms are often sufficient for standard EBB. The trend observed in the younger subgroup (<65 years) for ice-cold saline is intriguing; it may be hypothesized that younger vessels retain better contractile capacity in response to cold, whereas older, possibly more atherosclerotic or stiffened vessels, are less responsive.
Clinicians should consider these findings alongside the high cost and environmental footprint of routine pre-procedural testing. A more nuanced approach to bronchoscopy would involve: (1) selective pre-procedural screening for patients with known anticoagulation use or liver disease, (2) prioritizing endobronchial access where feasible, and (3) reserving haemostatic agents for therapeutic rather than prophylactic use, except perhaps in younger patients where ice-cold saline might offer a marginal benefit.
One limitation of the PROTECT study is its single-blind nature, which may introduce some bias in subjective bleeding scales, although the use of VAS helps standardize observations. Future research should focus on whether these findings hold true for higher-risk procedures, such as transbronchial cryobiopsy for interstitial lung disease, where bleeding risks are inherently higher than in central EBB.
Conclusion
The PROTECT study clarifies that routine prophylactic haemostatic treatment does not provide a universal advantage in controlling iatrogenic bleeding during endobronchial biopsy. While the safety of these agents is confirmed, their efficacy remains elusive for the general population, with only a slight trend in favor of ice-cold saline in younger cohorts. Modern interventional pulmonology must move toward a more personalized strategy—optimizing tool selection, adopting targeted pre-procedural screening, and utilizing advanced techniques like robotic assistance to maximize diagnostic yield while minimizing procedural risks. As we advance, the focus should shift from universal prophylaxis to precision-based procedural planning.
References
- Li B, et al. Prophylactic haemostatic treatment to control iatrogenic bleeding during endobronchial biopsy (PROTECT study): a multicentre, randomised, single-blind, placebo-controlled study. Chest. 2026. PMID: 41802594.
- Sader C, et al. Approaches for Lung Fiducial Markers Insertion in Stereotactic Body Radiotherapy: A Systematic Review and Meta-Analysis. J Bronchology Interv Pulmonol. 2026. PMID: 41738525.
- Nguyen P, et al. Accuracy of Rapid On-Site Evaluation in Robotic-Assisted Bronchoscopy Fine Needle Aspirations of Lung Nodules. J Bronchology Interv Pulmonol. 2026. PMID: 41718084.
- Smith M, et al. Routine Pathology Testing Prior to Bronchoscopy has Limited Clinical Impact With Significant Economic and Environmental Costs. J Bronchology Interv Pulmonol. 2026. PMID: 41549992.
- Chen Y, et al. Efficacy of High-Flow Nasal Cannula Oxygen Therapy During Bronchoscopy: A Systematic Review and Meta-Analysis. J Bronchology Interv Pulmonol. 2026. PMID: 41550007.