Abstract
Background:
Aspirin use has been shown to be safe for patients undergoing certain diagnostic bronchoscopy procedures such as transbronchial biopsies and endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration. However, there are no studies documenting the safety of aspirin in patients undergoing therapeutic bronchoscopy. The aim of this study is to evaluate whether aspirin increases the risk of bleeding following therapeutic bronchoscopy.
Methods:
This was a retrospective study to determine if there was a higher risk of bleeding in patients on aspirin undergoing therapeutic bronchoscopy compared with those not on aspirin. Patient characteristics were reported by cohort using the mean, median, and standard deviation for continuous variables, and using frequencies and relative frequencies for categorical variables.
Results:
Of the 108 patients who had multimodality therapeutic bronchoscopy, 17 (15.7%) were taking aspirin and 91 (84.3%) were not on aspirin. Patients in the aspirin group were older than those in the no aspirin group (median age: 66
Conclusion:
Aspirin use was not associated with increased risk of bleeding or procedure-related complications after therapeutic bronchoscopy.
Introduction
Aspirin is a widely used medication for a variety of conditions. It is used for primary and secondary prevention of cardiovascular diseases [Lewis et al. 1983; Bredie et al. 2003; Ye et al. 2010] and as an anti-inflammatory and analgesic for conditions like headaches, musculoskeletal pains and other rheumatologic diseases [Wluka et al. 2015]. As most lung cancers and other thoracic malignancies occur later in life, a significant number of patients presenting with airway involvement requiring bronchoscopic intervention are consuming aspirin for some of the indications mentioned above. Interventional pulmonologists therefore frequently encounter patients taking antiplatelet or anticoagulation drugs.
The safety of aspirin use in certain diagnostic bronchoscopic procedures like transbronchial biopsies has been well established [Herth et al. 2002]. A small case series revealed that patients using aspirin and clopidogrel safely, underwent endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration [Stather et al. 2012]. Therapeutic bronchoscopy is frequently performed to treat benign and malignant airway obstruction and potentially, there is a higher risk of bleeding as compared to a basic diagnostic bronchoscopy procedure. The traditional approach is to withhold anticoagulation agents, given the concern of bleeding and the lack of evidence in the literature supporting the safety of their continued use, during therapeutic bronchoscopic procedures. Sometimes, the decision to discontinue aspirin becomes challenging due to the risk of exacerbating underlying cardiovascular risks for which aspirin is being used. There is thus an important need to study and advance our understanding of the procedures that can be safely performed on aspirin. The aim of this study is to evaluate whether aspirin increases the risk of bleeding after therapeutic bronchoscopy.
Methods
Study population
The study protocol (BDR_051814) was approved by the Institutional Review Board of Roswell Park Cancer Institute, USA. Informed consent was waived due to the retrospective nature of the study. All successive patients who underwent advanced therapeutic bronchoscopy between August 2013 and April 2015 by the interventional pulmonary service at our institution were included, and their medical records were reviewed.
Use of aspirin
The pulmonary team did not advise any patient to discontinue taking aspirin prior to therapeutic bronchoscopy based on our earlier experience, where we did not see higher bleeding in this group. Patients who were taking other antiplatelet or anticoagulation agents were instructed to discontinue them before the procedure. Some patients stopped aspirin based on instructions of the preoperative anesthesia clinic while others opted to withhold aspirin on their own, due to perceived concern of bleeding. Subjects were considered to be on aspirin during therapeutic bronchoscopy if they had consumed aspirin within the preceding 48 hours.
The therapeutic bronchoscopy
All patients underwent bronchoscopy under general anesthesia with endotracheal intubation, laryngeal mask airway or rigid bronchoscopy using conventional ventilation. Manual jet ventilation was available if needed. The flexible therapeutic, regular and ultrathin bronchoscopes (Olympus America Inc., Center Valley, PA, USA) were used in most cases. The rigid bronchoscope and tracheoscope (Bryan Corporation, Woburn, MA, USA), argon plasma coagulation (APC, ERBE USA, Marietta, GA, USA), electrocautery (ERBE USA, Marietta, GA, USA), cryotherapy (ERBE USA, Marietta, GA, USA), or laser (Biolitec, Jena, Germany, Inc.) were also used in the majority of cases. Airway stenting was performed when indicated, primarily for central airway obstruction and aerodigestive fistulae. Silicone or self-expanding covered metallic stents were most commonly used. Other therapeutic bronchoscopic procedures like endobronchial valves, coils and bronchial thermoplasty are not commonly performed in our cancer center and were not assessed in this study. Estimated blood loss (EBL) was a part of the structured electronic bronchoscopy procedure note and also the nursing assessment sheet and was assessed at the end of each procedure by the performing bronchoscopist. There was no described specific methodology used to quantify the blood loss. It was rather an estimation based on visual observation by the proceduralist.
Statistical analysis
Patient characteristics were reported by cohort (aspirin/no aspirin) using the mean, median, and standard deviation for continuous variables, and using frequencies and relative frequencies for categorical variables. Comparisons were made using the Satterthwaite’s two-sided
Results
A total of 110 patients underwent therapeutic bronchoscopy between August 2013 and April 2015. A total of two procedures were performed while on clopidogrel and were excluded from the final analysis. Of the 108 patients included, 17 (15.7%) were taking aspirin during therapeutic bronchoscopy and 91 (84.3%) were not on aspirin. Of the 17 patients who were on aspirin, 16 were on 81 mg and one was on 325 mg of aspirin. Table 1 shows the patient characteristics of the aspirin and no aspirin groups who underwent therapeutic bronchoscopy. In the aspirin group, nine patients (53%) were using aspirin for secondary prevention with a personal history of coronary artery disease. The other eight patients were using aspirin for primary prevention of coronary artery disease. The indication for bronchoscopy was malignant or benign airway obstructive disease in the majority of patients (58.3%). Other indications included stent revision and management of carcinoma-
Patient characteristics by aspirin and no aspirin for bronchoscopy.
Patients in the aspirin group were older than in the no aspirin group (median age: 66
The distribution of expected blood loss (EBL) within each cohort is examined graphically using overlapping histograms. The association between aspirin and EBL, while adjusting for patient characteristics (age, gender, lung pathology, indication for bronchoscopy, total number of procedure modalities, clopidogrel and multivitamin use), was evaluated using ANCOVA; with the mean EBL compared using a test on the least square means. The means are presented with standard errors (SE) and the mean difference is estimated using a 95% confidence interval (CI). All model assumptions were verified graphically.
In the no aspirin group, 12 patients who were using aspirin had discontinued it more than five days before the procedure. A subgroup analysis showed no significant difference in EBL or complications between the 12 patients who had stopped aspirin and the 17 patients in the aspirin group.
Discussion
Our study showed that almost every fourth patient (29/108; 26.9%) undergoing therapeutic bronchoscopy for a variety of indications was an aspirin consumer. We also observed that a significant proportion of patients (12/29; 41.4%), discontinued aspirin in preparation for the procedure. This was perhaps because of lack of clear consensus or guidelines about the use of aspirin in therapeutic bronchoscopy. Since all patients undergoing therapeutic bronchoscopy also had a preoperative anesthesia evaluation, it is difficult to determine how many patients were instructed to stop aspirin and how many stopped on their own. The proceduralist did not instruct any patient to stop aspirin although it is possible that some high-risk cardiovascular patients may have been firmly instructed not to stop aspirin. The average number of multimodality bronchoscopic therapeutic modalities was fairly similar in patients whether on aspirin and not which suggests that the proceduralist were not more conservative in the aspirin group. APC was more commonly used in the no aspirin group which argues against the higher need of control of bleeding or oozing in the aspirin group. In spite of the use of multiple modalities, we did not observe any difference in amount of bleeding in the aspirin group. Similarly, it was reassuring to see that the rate of overall complications was not significantly different between groups.
A recent national survey revealed that approximately half of Americans above the middle-age group use aspirin regularly [Williams et al. 2015]. This corresponds to the age group of most patients presenting with lung cancers and other conditions requiring interventions. In a recent review about the use of aspirin in the perioperative period, Kiberd and Hall concluded that the management of aspirin in the preoperative period is complicated by a lack of evidence-based literature and therefore, the decision of withholding or continuing aspirin before a procedure ought to be made on a case-by-case risk–benefit evaluation [Kiberd and Hall, 2015].
Therapeutic bronchoscopy provides a minimally invasive way to treat a variety of airway diseases. Malignant and benign airway conditions can present with respiratory symptoms ranging from mild, such as cough or dyspnea on exertion, to severe, such as stridor and respiratory failure. Therapeutic bronchoscopy is commonly performed for palliation or to alleviate patient’s distress, pending definitive treatment [Ernst et al. 2004; Harris et al. 2015]. More than a single modality may be used during therapeutic bronchoscopy. The most commonly used modalities are: mechanical debulking using flexible or rigid bronchoscopy, laser photoresection, APC, cryotherapy, electrocautery, brachytherapy and photodynamic therapy (PDT) [Ernst et al. 2004]. In some benign conditions, therapeutic bronchoscopy can be offered as an alternative to other therapies, such as in bronchoscopic lung volume reduction using endobronchial valves or coils, bronchial thermoplasty for refractory asthma [Davey et al. 2015; Denner et al. 2015; Gompelmann et al. 2015] and endobronchial valves for persistent air leaks [Reed et al. 2015]. However the theoretical risk of bleeding in such cases is low compared with procedures involving debulking of tumors, or manipulating stents in vascular areas of airways involved with tumors.
The risk of bleeding in diagnostic bronchoscopy procedures while taking aspirin has been studied and reported in the literature. In a large prospective study by Herth and colleagues, the continuation of aspirin before transbronchial biopsy did not increase the risk of bleeding [Herth et al. 2002]. A total of 1217 patients were prospectively enrolled, 285 (23%) of whom used aspirin within 24 hours prior to the procedure. Less than 1% of patients suffered from severe bleeding. Moreover, all episodes of bleeding were controlled bronchoscopically without any mortality [Herth et al. 2002]. Based on the results of this study, aspirin use is generally considered to be well tolerated for transbronchial biopsies. The same may not be true for all antiplatelet agents. A clinical trial where transbronchial biopsies were performed on patients taking clopidogrel had to be terminated early due to excessive bleeding in patients on clopidogrel [Ernst et al. 2006]. Although small case series have confirmed the safety of EBUS-guided transbronchial needle aspiration while on dual antiplatelet therapy of aspirin and clopidogrel [Stather et al. 2012; Parks et al. 2014], others have reported significant bleeding [Karnyski et al. 2015]. Similarly, a recent case report demonstrated the safety of endobronchial biopsy while using aspirin and prasugrel [Harris and Kebbe, 2015] but overall there is a lack of clinical data to support decision making in such complex clinical scenarios.
Although the safety of aspirin use in diagnostic bronchoscopy is documented, there is a lack of studies addressing aspirin use and the associated risk of bleeding following therapeutic bronchoscopy. To the best of our knowledge, there are no studies or reports related to bleeding risks associated with therapeutic bronchoscopic interventions with the continued use of aspirin. Likewise, there is no evidence in the medical literature supporting the practice of discontinuing aspirin before therapeutic bronchoscopy. Our study is the first one to demonstrate that there is no difference in the risk of bleeding or in other complications, whether the procedure is performed while aspirin is used or not.
This study has several limitations, many of which are inherent due to the retrospective design of the study. This is a single-center experience and the sample size is small which makes it difficult to generalize the results. Most patients were on 81 mg of aspirin and the results may not be generalizable to patients taking higher doses. We only included patients in the aspirin group if they had taken aspirin within 48 hours of the procedure although the effects of aspirin can persist or more than 48 hours, although we did not see any higher risk of bleeding, even in the group of aspirin users who had stopped aspirin more than 48 hours before. It is also not clear why some patients stopped aspirin and others continued it but it could be due to some variability in anesthesia or patient preference as the proceduralist did not instruct any aspirin users to discontinue it. The aspirin users were slightly older which is likely due to higher use of aspirin in older patients but in spite of this more bleeding was not observed in this group. One important critique of the study could be that, it is not possible to accurately quantify the exact amount of blood loss during procedures. However estimating the blood loss is a common practice in surgical procedures. Although, some studies have utilized the need for selective interventions to manage bleeding (e.g. suctioning, wedging of scope in segment, bronchial blocker, intensive care admission) to categorize it into mild, moderate and severe bleeding but even that is not a very accurate method and could have considerable interobserver variability [Ernst et al. 2006]. The interventions to control bleeding may be different depending on whether flexible or rigid bronchoscopy is being used. Even though, the EBL may not be completely accurate, it gives a generalized idea of the amount of bleeding. One of the interventional pulmonologists (Kassem Harris) was personally present for most of these cases and therefore interpersonal variability should have been minimized. In spite of many limitations, this is still the first study suggesting that patients undergoing therapeutic bronchoscopy may be able to continue taking aspirin without any higher bleeding risks. Prospective randomized multicenter studies are warranted to corroborate these findings and to further develop the standards of clinical practice in this area.
Conclusion
This small retrospective single-center analysis suggests that aspirin use does not increase the risk of bleeding after therapeutic bronchoscopy. Larger prospective clinical trials are needed to provide additional corroborative evidence.
Footnotes
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Conflict of interest statement
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JK, KM, AK, KA and SSD have no personal or financial disclosures and no conflict of interest. KH and AHA are consultants for Cook Medical.