Phrenic Nerve Injury Post Catheter Ablation for Atrial Fibrillation

Payal Sen, MD¹ 

Uddalak Majumdar, MD² 

Ali Imran Saeed, MD¹

¹University of New Mexico

Albuquerque, NM USA

²Cleveland Clinic Foundation

Cleveland, Ohio USA

Abstract

Objective: Phrenic nerve injury (PNI) is a complication of catheter ablation treatment of atrial fibrillation (AF). This condition can mimic that of comorbid conditions like congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD).

Case details: A 77-year-old woman with past medical history of heart failure with preserved ejection fraction and mild COPD, presented with dyspnea for 8 days. One week ago, she had undergone radiofrequency catheter ablation for persistent symptomatic AF. After the ablation, she reported dyspnea during PCP and pulmonary office visits and was given increasing doses of diuretics and inhalers since her symptoms were attributed to acute exacerbation of heart failure in the setting of COPD. However, a chest x-ray showed elevation of the right hemidiaphragm, and she had a positive sniff test. She was thus diagnosed with right sided phrenic nerve palsy and was treated with oxygen therapy.

Discussion: Phrenic nerve injury can be diagnosed via clinical exam, chest x-ray and sniff test. A sniff Test which shows paradoxical elevation of the paralyzed hemidiaphragm with inspiration, compared with the rapid descent of the normal hemidiaphragm.

Conclusion: Phrenic nerve palsy is a complication which occurs in 6.6 percent of cases, post catheter ablation procedure for atrial fibrillation. This condition can mimic pulmonary conditions like acute exacerbation of COPD. Not keeping this complication in mind can lead to biased diagnostic reasoning and missed or delayed diagnosis.

Introduction

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia (1). In the past decade, catheter ablation of AF has evolved from an investigational procedure to a frequent therapeutic one (2). Phrenic nerve injury (PNI) is a complication of ablation that pulmonologists should be familiar with, due to its increasing incidence (3). This condition can mimic that of comorbid conditions like congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD). Hence it is important to develop clinical suspicion of phrenic nerve injury, and correlate onset of symptoms to the ablation, to prevent missed or delayed diagnosis, and to avoid falling prey to availability bias.

Case Report

History of Present Illness: A 77-year-old Caucasian woman with past medical history of heart failure with preserved ejection fraction and mild COPD (GOLD Stage 1), presented with dyspnea and right sided chest discomfort for 7 days. One week ago, she had undergone radiofrequency catheter ablation at the University of New Mexico, for persistent symptomatic AF. After the ablation, she reported dyspnea during PCP and pulmonary office visits, which was attributed to acute exacerbation of heart failure in the setting of COPD. She had been given increasing doses of diuretics which did not relieve her symptoms. A short course of azithromycin and prednisone had also been prescribed for possible acute exacerbation of COPD, but her symptoms had remained unchanged. Review of systems were negative for fever, chills, cough, leg swelling and hemoptysis. She led an active lifestyle, did not require oxygen, and had quit smoking 10 years ago. There was no history of cardio- respiratory diseases in the family.

Physical Examination:

Vitals: Temperature: 97.1°F, Pulse – 88/minute, RR 22/minute, BP –

140/70 mm Hg., Spo2 – 90% in Room air (baseline >95 percent).

She appeared to be in mild distress. Baseline dry weight had not increased. She had no clinical signs of heart failure- no peripheral edema, no JVD, no S3, no bibasilar crackles. There were decreased breath sounds in the base of the right lung but no rales or rhonchi. No significant wheezing was heard in any of the lobes of the lungs.

No clubbing or cyanosis was noted. The rest of the exam was unremarkable with a normal abdominal, and skin exam. There was no lymphadenopathy.

Laboratory: White blood cell count 10,000/mm³, hemoglobin 11 g/dL, with normal electrolytes, liver function tests and negative troponins. Arterial blood gases on room air showed a pH 7.38, paO2 of 62 mm Hg, pCO2 41 mm Hg and HCO3^- 25.

EKG: negative for signs of ischemia.

Radiography: Chest radiography showed an elevated right diaphragm (Figure 1).

Figure 1. A: PA chest radiograph and B: 3 weeks earlier for comparison.

Sniff test performed under fluoroscopy showed paradoxical elevation of the right hemidiaphragm with inspiration, compared with rapid descent of the left hemidiaphragm, confirming right hemidiaphragm paralysis (Figure 2).

Figure 2. Static images from sniff test under fluoroscopy: A: pre-sniff. B: post-sniff. When the patient sniffs in, the left hemidiaphragm moves downwards but right hemidiaphragm does not (actually moves upwards very slightly).

After obtaining proper imaging, the patient was finally diagnosed with right-sided diaphragmatic paralysis due to phrenic nerve injury from the catheter ablation procedure done to treat AF. She was discharged with home oxygen and her symptoms have resolved. Follow up clinic visits revealed complete resolution of symptoms.

Discussion

Ectopic discharges from pulmonary veins are an important cause of atrial fibrillation, the most common sustained cardiac arrhythmia (1). Calkins et al. (4) carried out a study in 2009, where they showed statistically significant improvement in symptoms and quality of life in patients receiving ablation therapy versus those patients who received anti arrhythmic drugs (4). Traditionally, isolating the pulmonary vein by point-by-point radiofrequency catheter ablation was the cornerstone of catheter ablation strategies for the treatment of atrial fibrillation (2). However, this procedure had various complications such as thromboembolism, cardiac perforation, injury to adjacent structures and pulmonary vein stenosis (5). Hence, with the hope of finding an effective alternative approach with less complications, cryothermal ablation was started. This particular procedure involves electrically isolating pulmonary veins, by creating circumferential lesions by means of a cryoballoon catheter (6). Nonetheless, in both techniques, the most common complication is hemi‐diaphragmatic paralysis, due to phrenic nerve injury. This especially occurs whilst trying to isolate the right superior pulmonary vein (3). The approximate incidence of this complication is close to 3–11% (7). It is thought that the phrenic nerve gets injured due to the close anatomic relationship of the phrenic nerve to the heart (Figure 3).

Figure 3. Thoracic CT scan showing anatomical relationships (yellow star is the right phrenic nerve).

Both the right and the left phrenic nerves can get damaged - the right phrenic nerve is specifically at risk when ablations are carried out in the superior caval vein and the right superior pulmonary vein, and the left phrenic nerve is liable to damage during lead implantation into the great cardiac and left obtuse marginal veins (8). In our patient, the right phrenic nerve, which runs along the lateral surfaces of the superior vena cava and right atrium, was injured by energy delivered to the adjacent area during ablation.

In 2005 Bunch et al. (9) investigated the specific mechanism of phrenic nerve injury. Their study revealed that the phrenic nerve tended to retain heat after ablation. This phenomenon resulted in higher local temperatures with subsequent energy deliveries, causing early transient injury. Andrade et al. (3) in 2014, were the first to define this phrenic nerve injury histopathologically. According to them, phrenic nerve injury consisted of Wallerian degeneration characterized by loss of large myelinated axons with variable degrees of endoneural edema, vacuolated macrophages, myelin ovoids, and myelin digestion chambers (6).

Phrenic nerve injury can be diagnosed on clinical exam, and via a chest X-ray. Thereafter one can confirm the diagnosis with the sniff test or phrenic nerve stimulation/diaphragm electromyography. An upright chest x-ray will reveal an elevated diaphragm on the affected side. This test is sensitive, but not specific for the diagnosis of unilateral diaphragmatic paralysis (10). Another frequently done test is the sniff test which shows paradoxical elevation of the paralyzed hemidiaphragm with inspiration, compared with the rapid descent of the normal hemidiaphragm (11). The sniff test has more than 90 percent sensitivity (11). In 2014, Linhart et al. (12) performed studies to show that fluoroscopic assessment of diaphragm movement during spontaneous breathing was more sensitive for the diagnosis of phrenic nerve injury as compared to SVC pacing (12). It has also been seen that EMG‐guided approach results in less damage to the phrenic nerve and a significant reduction in hemi‐diaphragmatic paralysis as compared to current methods of abdominal palpation and fluoroscopy (13).

In unilateral diaphragmatic paralysis, patients are usually asymptomatic, have good prognosis and do not always need treatment. This is specifically true in the absence of underlying lung disease (14). Another procedure often done is the surgical plication of the affected hemidiaphragm (15). In bilateral diaphragm paralysis, ventilatory failure often occurs and these patients may require continuous positive airway pressure or mechanical ventilation and tracheostomy (16). According to Kauffman (17) in 2014, functional restoration of the paralyzed diaphragm should also be part of the standard treatment algorithm in managing symptomatic patients.

Conclusion

Phrenic nerve palsy is a complication which occurs in about 6 percent of cases post catheter ablation procedure for atrial fibrillation. This condition can mimic pulmonary conditions like acute exacerbation of COPD. It is important to develop clinical suspicion and correlate onset of symptoms to the ablation. Not keeping this complication in mind can lead to biased diagnostic reasoning and missed or delayed diagnosis.

References

1. Yamazaki M, Filgueiras-Rama D, Berenfeld O, Kalifa J. Ectopic and reentrant activation patterns in the posterior left atrium during stretch-related atrial fibrillation. Prog Biophys Mol Biol. 2012 Oct-Nov;110(2-3):269-77. [CrossRef] [PubMed]
2. Pedrote A, Acosta J, Jauregui-Garrido B, Frutos-Lopez M, Arana-Rueda E. Paroxysmal atrial fibrillation ablation: Achieving permanent pulmonary vein isolation by point-by-point radiofrequency lesions. World J Cardiol. 2017 Mar 26;9(3):230-40. [CrossRef] [PubMed]
3. Andrade JG, Dubuc M, Ferreira J, Guerra PG, Landry E, Coulombe N, et al. Histopathology of cryoballoon ablation-induced phrenic nerve injury. J Cardiovasc Electrophysiol. 2014 Feb;25(2):187-94. [CrossRef] [PubMed]
4. Calkins H, Reynolds MR, Spector P, et al.  Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and metaanalyses. Circ Arrhythm Electrophysiol. 2009 Aug;2(4):349-61. [CrossRef] [PubMed]
5. Sarabanda AV, Bunch TJ, Johnson SB, et al. Efficacy and safety of circumferential pulmonary vein isolation using a novel cryothermal balloon ablation system. J Am Coll Cardiol. 2005 Nov 15;46(10):1902-12. [CrossRef] [PubMed]
6. Andrade JG, Khairy P, Guerra PG, et al. Efficacy and safety of cryoballoon ablation for atrial fibrillation: a systematic review of published studies. Heart Rhythm. 2011 Sep;8(9):1444-51. [CrossRef] [PubMed]
7. Omran H, Gutleben KJ, Molatta S, et al. Second generation cryoballoon ablation for persistent atrial fibrillation: an updated meta-analysis. Clin Res Cardiol. 2018 Feb;107(2):182-92. [CrossRef] [PubMed]
8. Sanchez-Quintana D, Cabrera JA, Climent V, Farre J, Weiglein A, Ho SY. How close are the phrenic nerves to cardiac structures? Implications for cardiac interventionalists. J Cardiovasc Electrophysiol. 2005 Mar;16(3):309-13. [CrossRef] [PubMed]
9. Bunch TJ, Bruce GK, Mahapatra S, et al. Mechanisms of phrenic nerve injury during radiofrequency ablation at the pulmonary vein orifice. J Cardiovasc Electrophysiol. 2005 Dec;16(12):1318-25. [CrossRef] [PubMed]
10. Chetta A, Rehman AK, Moxham J, Carr DH, Polkey MI. Chest radiography cannot predict diaphragm function. Respir Med. 2005 Jan;99(1):39-44. [CrossRef] [PubMed]
11. Alexander C. Diaphragm movements and the diagnosis of diaphragmatic paralysis. Clin Radiol. 1966 Jan;17(1):79-83. [CrossRef] [PubMed]
12. Linhart M, Nielson A, Andrie RP, et al. Fluoroscopy of spontaneous breathing is more sensitive than phrenic nerve stimulation for detection of right phrenic nerve injury during cryoballoon ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2014 Aug;25(8):859-65. [CrossRef] [PubMed]
13. Miyazaki S, Ichihara N, Nakamura H, et al. Prospective evaluation of electromyography-guided phrenic nerve monitoring during superior vena cava isolation to anticipate phrenic nerve injury. J Cardiovasc Electrophysiol. 2016 Apr;27(4):390-5. [CrossRef] [PubMed]
14. Piehler JM, Pairolero PC, Gracey DR, Bernatz PE. Unexplained diaphragmatic paralysis: a harbinger of malignant disease? J Thorac Cardiovasc Surg. 1982 Dec;84(6):861-4. [PubMed]
15. Kuniyoshi Y, Yamashiro S, Miyagi K, Uezu T, Arakaki K, Koja K. Diaphragmatic plication in adult patients with diaphragm paralysis after cardiac surgery. Ann Thorac Cardiovasc Surg. 2004 Jun;10(3):160-6. [PubMed]
16. Davis J, Goldman M, Loh L, Casson M. Diaphragm function and alveolar hypoventilation. Q J Med. 1976 Jan;45(177):87-100. [PubMed]
17. Kaufman MR, Elkwood AI, Colicchio AR, et al. Functional restoration of diaphragmatic paralysis: an evaluation of phrenic nerve reconstruction. Ann Thorac Surg. 2014 Jan;97(1):260-6. [CrossRef]

Cite as: Sen P, Majumdar U, Saeed AI. Phrenic nerve injury post catheter ablation for atrial fibrillation. Southwest J Pulm Crit Care. 2018;16(6):362-7. doi: https://doi.org/10.13175/swjpcc070-18 PDF 

November 2016 Pulmonary Case of the Month

November 2016 Pulmonary Case of the Month

Anjuli M. Brighton, MB, BCh, BAO

Tania Jain, MBBS

Alan H. Bryce, MD

Ramachandra R. Sista, MD

Robert W. Viggiano, MD

Lewis J. Wesselius, MD

Pulmonary and Hematology/Oncology Departments

Mayo Clinic Arizona

Scottsdale, AZ USA

Pulmonary Case of the Month CME Information

Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive 0.25 AMA PRA Category 1 Credits™ for each case they complete. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity. 

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours

Lead Author(s): Anjuli M. Brighton, MB.  All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.

Learning Objectives:
As a result of this activity I will be better able to:

1. Correctly interpret and identify clinical practices supported by the highest quality available evidence.
2. Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
4. Will integrate new treatment options in discussing available treatment alternatives for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine at Banner University Medical Center Tucson

Current Approval Period: January 1, 2015-December 31, 2016

Financial Support Received: None

History of Present Illness

Our patient is a 76-year-old gentleman  who was referred based on an abnormal CT scan. He has a history of metastatic melanoma and had begun immunotherapy with pembrolizumab 10 months prior to admission. He had low grade fevers and chills and some dyspnea on exertion and dry cough. He also had a 6-8 pound weight loss over 4 weeks.

PMH, SH and FH

He has a history of hairy cell leukemia since 2009; squamous and basal cell cancers; and diabetes on insulin. He is a retired commercial banker and has a 15 pack-year smoking history.

Physical Examination

Physical examination showed and SpO2 of 90% on room air. His lungs were clear. He had numerous depigmented lesions on his skin.

Radiography

A thoracic CT scan was performed (Figure 1) and compared to a scan done 3 months prior which was considered unremarkable.

Figure 1. Video of representative images of contrast-enhanced thoracic CT scan in lung windows.

Which of the following best describe the CT scan? (Click on the correct answer to proceed to the second of four pages)

1. Normal
2. Mosaic pattern of lung attenuation
3. Numerous bronchial-associated ground glass opacities
4. Numerous pulmonary nodules
5. Numerous pulmonary nodules with a halo sign

Cite as: Brighton AM, Jain T, Bryce AH, Sista RR, Viggiano RW, Wesselius LJ. November 2016 pulmonary case of the month. Southwest J Pulm Crit Care. 2016:13(5):191-5. doi: http://dx.doi.org/10.13175/swjpcc098-16 PDF

January 2016 Pulmonary Case of the Month

Kathryn E. Williams, MB

Karen L. Swanson, DO 

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 64-year-old man was seen in June 2015 with a nonproductive cough.

Past Medical History, Social History and Family History

He has no significant past medical history. He is a former smoker. Family history is positive for coronary artery disease

Physical Examination

Decreased breath sounds over the right hemithorax with dullness to percussion. Otherwise, the physical exam is unremarkable.

Radiography

A chest radiograph was performed (Figure 1).

Figure 1. Initial PA chest radiograph.

The chest radiograph shows which of the following? (Click on the correct answer to proceed to the second of five panels)

1. There is a large mass in the right upper lobe
2. There is a loculated pleural effusion
3. There is volume loss in the right upper lobe
4. 1 and 3
5. All of the above

Cite as: Williams KE, Swanson KL. January 2016 pulmonary case of the month. Southwest J Pulm Crit Care. 2016;12(1):1-5. doi: http://dx.doi.org/10.13175/swjpcc158-15 PDF 

Safety and Complications of Bronchoscopy in an Adult Intensive Care Unit

Aarthi Ganesh, MBBS¹

Nirmal Singh, MBBS, MPH²

Gordon E. Carr, MD¹

¹Department of Pulmonary & Critical Care

²Department of Internal Medicine

University of Arizona

Tucson, Arizona

Abstract

Background: Bronchoscopy is a common procedure performed in adult intensive care units (ICU). However, very few studies report the safety and complications of the bronchoscopy and related procedures performed on critically ill patients. The primary aim of this study was to determine the incidence of complications following ICU bronchoscopy.

Methods: We conducted a retrospective chart review of patients admitted to an adult ICU and underwent bronchoscopy with or without bronchoalveolar lavage (BAL) and other bronchoscopic procedures. Data included patient demographics, APACHE II score, hemodynamics, comorbidities, type of ventilation and procedure performed. Data from BAL, including cellular differential and microbiology, were also collected.

Results: We identified 120 patient charts between November 2011 to March 2012. The most common procedure was bronchoscopy with BAL (62%) to evaluate for pneumonia (58%). Other procedures included transbronchial biopsy, APC and cryotherapy, balloon and stent placement, endobronchial biopsy and EBUS. Complications occurred in 18% of the patients, with hypoxia being the most common (7.5%). No deaths occurred related to the procedures. Nine percent of patients who had BAL or inspection had complications compared to 29% who underwent other procedures. Subgroup analysis conducted on patients undergoing BAL revealed significantly higher neutrophil counts (p=0.001) and higher APACHE II score (p=0.02) among those with BAL positive for bacteria and co-infection.

Conclusion: Bronchoscopy with BAL and inspection is relatively safe procedure even in critically ill patients. However, other interventional bronchoscopic procedures should be performed with caution in the ICU.

Abbreviations:

ICU: Intensive care unit

BAL: Bronchoalveolar lavage

EBUS: Endobronchial Ultrasound

APC: Argon Plasma Coagulation

SBP: Systolic Blood Pressure

CI: Confidence Interval

IP: Interventional pulmonary

MAP: Mean arterial pressure

SD: Standard deviation

CHF: Congestive heart Failure

COPD: Chronic Obstructive Pulmonary Disease

ILD: Interstitial Lung Disease

ET: Endotracheal

Introduction

Fiberoptic bronchoscopy is a commonly performed procedure in the medical intensive care unit (ICU). Prior studies have indicated that bronchoscopy is generally safe, making it a relatively low-risk procedure in appropriately selected ICU patients (1-3). Most prior studies reporting the safety of bronchoscopy were performed in early 1990s. The rates of complications or adverse events in these earlier studies ranged from 2% to 40% (2,4-6). The primary aim of this study was to assess the incidence of complications in ICU patients undergoing bronchoscopy in the contemporary era.

Methods

The study was approved by the Institutional Review Board at the University of Arizona. We conducted a retrospective chart review of patients, 18 years or older, admitted to the adult medical intensive care unit, who underwent bronchoscopy with or without bronchoalveolar lavage (BAL) and other bronchoscopic procedures from November 1, 2011 to March 31, 2012. The other bronchoscopic procedures included transbronchial biopsies, endobronchial ultrasound (EBUS) guided biopsy, argon plasma coagulation (APC) and cryotherapy, balloon dilatation with stenting, and endobronchial biopsy. We excluded patients with incomplete charts, and patients who had bronchoscopy as a part of percutaneous tracheostomy procedure. Data included patient demographics, APACHE II scores, hemodynamics, co-morbidities, type of ventilation, type of procedure performed and the complications. Sedation used in the procedures included propofol or midazolam with fentanyl for analgesia. BAL results, including cellular differential and microbiology studies, were also collected. We used pre-specified definitions to assess for complications. We defined hypotension as reduction in systolic blood pressure (SBP) by >20 mm Hg or when a patient required vasopressors to maintain a mean arterial pressure (MAP) > 60 mm Hg during or after the procedure. Hypoxia was defined by drop in saturation to < 90% or when the FiO2 requirement increased by > 20% for more than 2 hours after the procedure. Hemorrhage was indicated as per the procedure note by the bronchoscopist or when the note indicated use of epinephrine or when additional procedures needed to be performed to control the bleeding. During the procedure all the patients FiO2 was increased but was turned down to their previous ventilatory settings unless there was significant hypoxia.

Statistical analysis was performed using STATA/IC 13.1 (StataCorp LP, Texas). Numerical variables are expressed as mean ± standard deviation (SD). Ninety-five percent confidence intervals (CIs) were calculated where appropriate. Univariate comparisons between patients who did and did not develop complications were calculated using a χ2 test or Fischer's exact test for categorical variables and a 2-sample t test for continuous variables applying central limit theorem. All statistical testing was two-tailed with significance level set at the alpha level of ≤0.05.

Results

We identified 140 patients who underwent ICU bronchoscopy during the study period. Eighteen patients were excluded due to incomplete information. Two charts were excluded as the bronchoscopy was performed for percutaneous tracheostomy. Table 1 shows the baseline characteristics of patients undergoing ICU bronchoscopy.

Table 1. Baseline Characteristics of Patients Prior to Bronchoscopy

Key: CAD: Coronary Artery Disease

        CHF: Congestive Heart Failure

        COPD: Chronic obstructive pulmonary disease

        FiO2: Oxygen required

        ILD: Interstitial Lung Disease

        MAP: Mean arterial pressure

        NM Disease: Neuromuscular disease

Sixty-nine percent of the patients were male and average age was 52 ± 16 years. The average APACHE II score was 18 ± 6 with a median of 18 and 88% of the patients were intubated and mechanically ventilated. The mean percentage oxygen (FiO2) requirement in the patients prior to the procedure was 63% ± 26. Sixty-three percent of the patients were immunocompromised, likely related to the large proportion of lung transplant recipients in our study population. Fifty-four percent also had chronic lung disease including chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Other common co-morbidities included cardiovascular disease including congestive heart failure (CHF) and arrhythmias, malignancy and neuromuscular diseases. Table II shows the indications for ICU bronchoscopy. The most common indication for the procedure was to evaluate for pneumonia or infiltrate in 87 cases (72%), followed by atelectasis/ collapse/ secretions in 19 cases (15.8%) (Table 2).

Table 2. Indications For Procedures

Other indications included tracheal or airway diseases, which included tracheal stenosis, upper airway obstruction, tracheal mass and bronchopleural fistula in 11 (8%) and hemoptysis (2%). The most common procedures performed were bronchoscopy with BAL in 75 (62%) and inspection in 31 (26%) (Table 3).

Table 3. Procedures

Key:  APC: Argon plasma coagulation

         BAL: Bronchoalveolar lavage

         Cryo: Cryotherapy

         EBUS: Endobronchial ultrasound

         ET: Endotracheal tube

Other procedures included transbronchial biopsy, APC and cryotherapy, balloon and stent placement, endobronchial biopsy and EBUS.

Table 4 shows the complications resulting from ICU bronchoscopy in this study population.

Table 4. Complications

Twenty two complications occurred during or within 2 hours after the procedure (18%), with hypoxia being the most common (7.5%). Hypoxia in two patients occurred secondary to hemorrhage. Pneumothorax was seen in one patient who underwent transbronchial biopsy with no fluoroscopic guidance. Hypotension which needed treatment with fluids or vasopressors occurred in 5.8% and hemorrhage in 3.3%. Hemorrhage was unrelated to coagulopathy in the patients. Significant bradycardia requiring treatment with atropine occurred in one patient. No deaths were reported related to the procedures. None of the procedures had to be terminated secondary to the complications. More adverse events were seen among the patients who underwent other bronchoscopic procedures (29%) than those undergoing BAL or inspection only (9%), though this was not statistically significant (p = 0.07).

As depicted in Table 5, none of the complications were significantly affected by the underlying comorbidities or the APACHE scores.

Table 5. Patient Characteristics Stratified by Complications

Key: BAL: Bronchoalveolar lavage

       MAP: Mean Arterial Pressure

Complications were not significantly associated with the amount of oxygen required (FiO2) and the mode of ventilation which the patients were on prior to the procedure. Similarly, neither the mean arterial pressure before the procedure or coagulopathy influenced the rate of complications. Hospital mortality was not different in the group with or without complications.

Figure 1 and Table 6 show the BAL cell differential.

Figure 1. BAL differential in culture with normal respiratory flora (0), bacteria (1), Viral (2), Fungal (3) and Co-infection (4). Each bar represents the differential in percentage.

Key: BAL: Bronchoalveolar lavage

          BAL N: Neutrophil count in BAL (in percentage)

          BAL L: Lymphocyte count in BAL (in percentage)

          BAL M: Macrophages count in BAL (in percentage)

          BAL E: Eosinophils count in BAL (in percentage)

Table 6. Bronchoalveolar Lavage Differential

Patients found to have bacterial pneumonia or mixed viral and bacterial infection had significantly higher neutrophil counts (mean BAL neutrophil count 82% for bacterial infection, and 80% for co-infections) than other patients (p=0.001) (Figure 2).

Figure 2. Neutrophil predominance in bacterial pneumonia. KEY: BAL-N: Bronchoalveolar lavage, neutrophil differential (in percentage).

These patients also had a higher APACHE II score (p=0.02). Hospital mortality was higher among those with BAL positive for bacteria (p= 0.012). Mortality was also significantly higher among patients with underlying malignancy (p= 0.002).

Discussion

In our study of 120 ICU bronchoscopies, we found a complication rate of 18%. No deaths were observed in this study. Hypoxia was the most common adverse event in our study, occurring in 9 procedures (7.5%) as has been noticed in the previous studies. Introduction of a bronchoscope through an endotracheal (ET) tube is known to cause airway obstruction resulting in increasing intra-tracheal pressures and variation in respiratory physiology (6). Almost all the patients who were mechanically ventilated had a size 7.5 - 8.5 ET tube or had tracheostomy in place. As in prior studies, BAL performed for evaluation of pneumonia and atelectasis were the two most common indications of the procedure (72% and 15.8% respectively) in our study (1-7). Even though bronchoscopy has not shown to be routinely superior to chest physiotherapy, certain subset of patient population may benefit from it (3,8,9). Improvement in oxygenation has been shown to occur in certain earlier studies (10,11).

Hypotension is also a known complication occurring during bronchoscopy. Our study had 7 events (5.8%) of hypotension needing vasopressor or fluid infusion. This was likely related to the sedation. Hypertension was observed in one case and bradycardia requiring treatment was seen in one. Cardiovascular abnormalities associated with bronchoscopy is generally related to the sympathetic surge happening during the procedure and the hypoxia (12-14). Per earlier studies, the complication rate of transbronchial biopsies in mechanically ventilated patients range between 0-15% (15,16,17). But it is relatively safe in comparison to open lung biopsy.

With the advent of newer technology, there has been an increase in the number of other bronchoscopic interventional pulmonary (IP) procedures, including endobronchial ablative therapies such as APC and cryotherapy. Endobronchial lesions occupying more than 50% of the airway lumen can alter the airway physiology and result in hypoxia, ventilation perfusion mismatch and hence respiratory failure. Use of ablative therapies can potentially reverse this (18). APC has been an useful tool to remove endobronchial lesions and relieve obstruction. It has been shown to be efficient and relatively safe in outpatient setting, but APC on mechanically ventilated patients has not been very well studied (19). APC in mechanically ventilated patient requires decrease in the FiO2 to less than or equal to 40%. Complications related to IP procedures performed specifically in patients requiring mechanical ventilation are difficult to assess  from the available literature (20). However, given the complexity of these cases and underlying illness, usually the complications are minor. In our study, interventional bronchoscopy procedures like APC, cryotherapy was to relieve airway obstruction which was the cause of mechanical ventilation. In our study, APC case was associated with hemorrhage. The balloon dilatation and stenting which was performed for a case of tracheal stenosis arising from malignancy. This was not associated with any complications related to the procedure in our study. Further study is needed to refine our understanding of the risks of advanced bronchoscopic techniques in ICU patients.

Procedures like EBUS are usually not done in critically ill patients. There are no studies which have looked into the use of and complications of performing EBUS in critically ill patients. Bhaskar et al. (21) report the use of esophageal access for mediastinal sampling through EBUS in ICU patients for the reason of causing hypoxia and changes in airway physiology with the EBUS scope in airway. Our study had one patient who had an EBUS for lung mass and this was not associated with any complications.

Subgroup analysis in our study showed the presence of neutrophilic predominance with neutrophil count of >80% in the BAL differential in patients diagnosed with bacterial infections and co-infections compared to those with viral/ fungal or mixed flora (p=0.001). This was similar to results from earlier studies (22,23). Neutrophilic pleocytosis in BAL fluid is frequently found in patients with pneumonia. As the neutrophil count is higher in bacterial pneumonia, it can indicate towards a differential of bacterial pneumonia even prior to the final microbiology results. Hence BAL differential may be complimentary to final culture results and maybe helpful to initiate or discontinue antibiotics in critically ill patients. Mortality among critically ill patients with bacterial pneumonia was higher compared to others (p=0.012). These patients tend to be sicker with higher APACHE II scores.

The weaknesses of the study includes the fact that it was retrospective chart review. The total number is small, and the number of the IP procedures performed is even smaller. Hence it is important that more studies should be conducted looking into the safety and complications of IP procedures in critically ill patients.

Conclusion

Our study looked into the fiberoptic bronchoscopy with BAL and inspection as well as other therapeutic procedures done in the critically ill patients. It indicates that even in critically ill patients, bronchoscopy with inspection and BAL is safe. Other interventional pulmonary procedures may have more complications. Even though the number of IP procedures performed in the study is low, the evidence of slightly more number of complications with these procedures indicates the need for caution before attempting them in the critically ill patients.

References

1. Barrett CR Jr. Flexible fiberoptic bronchoscopy in the critically ill patient. Methodology and indications. Chest. 1978;73(5 Suppl):746-9. [CrossRef] [PubMed]
2. Hertz MI, Woodward ME, Gross CR, Swart M, Marcy TW, Bitterman PB. Safety of bronchoalveolar lavage in the critically ill, mechanically ventilated patient. Crit Care Med. 1991;19(12):1526-32. [CrossRef] [PubMed]
3. Olopade CO, Prakash UB. Bronchoscopy in the critical-care unit. Mayo Clin Proc. 1989;64(10):1255-63. [CrossRef] [PubMed]
4. Steinberg KP, Mitchell DR, Maunder RJ, Milberg JA, Whitcomb ME, Hudson LD. Safety of bronchoalveolar lavage in patients with adult respiratory distress syndrome. Am Rev Respir Dis. 1993;148(3):556-61. [CrossRef] [PubMed]
5. Prebil SE, Andrews J, Cribbs SK, Martin GS, Esper A. Safety of research bronchoscopy in critically ill patients. J Crit Care. 2014;29(6):961-4. [CrossRef] [PubMed]
6. Guerreiro da Cunha Fragoso E, Gonçalves JM. Role of fiberoptic bronchoscopy in intensive care unit: current practice. J Bronchology Interv Pulmonol. 2011;18(1):69-83. [CrossRef] [PubMed]
7. Raoof S, Mehrishi S, Prakash UB. Role of bronchoscopy in modern medical intensive care unit. Clin Chest Med. 2001;22(2):241-61, vii. [CrossRef] [PubMed]
8. Kreider ME, Lipson DA. Bronchoscopy for atelectasis in the ICU: a case report and review of the literature. Chest. 2003;124(1):344-50. [CrossRef] [PubMed]
9. Marini JJ, Pierson DJ, Hudson LD. Acute lobar atelectasis: a prospective comparison of fiberoptic bronchoscopy and respiratory therapy. Am Rev Respir Dis. 1979;119(6):971-8. [PubMed]
10. Snow N, Lucas AE. Bronchoscopy in the critically ill surgical patient. Am Surg. 1984;50(8):441-5. [PubMed]
11. Stevens RP, Lillington GA, Parsons GH. Fiberoptic bronchoscopy in the intensive care unit. Heart Lung. 1981;10(6):1037-45. [PubMed]
12. Katz AS, Michelson EL, Stawicki J, Holford FD. Cardiac arrhythmias. Frequency during fiberoptic bronchoscopy and correlation with hypoxemia. Arch Intern Med. 1981;141(5):603-6. [CrossRef] [PubMed]
13. Lindholm CE, Ollman B, Snyder JV, Millen EG, Grenvik A. Cardiorespiratory effects of flexible fiberoptic bronchoscopy in critically ill patients. Chest. 1978;74(4):362-8. [CrossRef] [PubMed]
14. Trouillet JL, Guiguet M, Gibert C, Fagon JY, Dreyfuss D, Blanchet F, Chastre J. Fiberoptic bronchoscopy in ventilated patients. Evaluation of cardiopulmonary risk under midazolam sedation. Chest. 1990;97(4):927-33. [CrossRef] [PubMed]
15. Bulpa PA, Dive AM, Mertens L, Delos MA, Jamart J, Evrard PA, Gonzalez MR, Installé EJ. Combined bronchoalveolar lavage and transbronchial lung biopsy: safety and yield in ventilated patients. Eur Respir J. 2003;21(3):489-94. [CrossRef] [PubMed]
16. O'Brien JD, Ettinger NA, Shevlin D, Kollef MH. Safety and yield of transbronchial biopsy in mechanically ventilated patients. Crit Care Med. 1997;25(3):440-6. [CrossRef] [PubMed]
17. Casal RF, Ost DE, Eapen GA. Flexible bronchoscopy. Clin Chest Med. 2013;34(3):341-52. [CrossRef] [PubMed]
18. Seaman JC, Musani AI. Endobronchial ablative therapies. Clin Chest Med. 2013;34(3):417-25. [CrossRef] [PubMed]
19. Morice RC, Ece T, Ece F, Keus L. Endobronchial argon plasma coagulation for treatment of hemoptysis and neoplastic airway obstruction. Chest. 2001;119(3):781-7. [CrossRef] [PubMed]
20. Boyd M, Rubio E. The utility of interventional pulmonary procedures in liberating patients with malignancy-associated central airway obstruction from mechanical ventilation. Lung. 2012;190(5):471-6. [CrossRef] [PubMed]
21. Bhaskar N, Shweihat YR, Bartter T. The intubated patient with mediastinal disease--a role for esophageal access using the endobronchial ultrasound bronchoscope. J Intensive Care Med. 2014;29(1):43-6. [CrossRef] [PubMed]
22. Stolz D, Stulz A, Müller B, Gratwohl A, Tamm M. BAL neutrophils, serum procalcitonin, and C-reactive protein to predict bacterial infection in the immunocompromised host. Chest. 2007;132(2):504-14. [CrossRef] [PubMed]
23. Choi SH, Hong SB, Hong HL, Kim SH, Huh JW, Sung H, Lee SO, Kim MN, Jeong JY, Lim CM, Kim YS, Woo JH, Koh Y. Usefulness of cellular analysis of bronchoalveolar lavage fluid for predicting the etiology of pneumonia in critically ill patients. PLoS One. 2014;9(5):e97346. [CrossRef] [PubMed]

Cite as: Ganesh A, Singh N, Carr GE. Safety and complications of bronchoscopy in an adult intensive care unit. Southwest J Pulm Crit Care. 2015;11(4):156-66. doi: http://dx.doi.org/10.13175/swjpcc106-15 PDF

Role of Endobronchial Ultrasound in the Diagnosis and Management of Bronchogenic Cysts: Two Case Descriptions and Literature Review

Rene Franco-Elizondo MD

Soumya Patnaik MD

Kuan-Hsiang Gary Huang MD, PhD

Jorge Mora MD

Albert Einstein Medical Center

Philadelphia, Pennsylvania

Abstract

Imaging studies, such as high resolution computerized tomography (HRCT) and magnetic resonance imaging (MRI) facilitate the evaluation of mediastinal masses. However, the definite characterization of such masses can be ascertained only after tissue sampling is obtained and analyzed. Some mediastinal masses, like bronchogenic cysts, can be misdiagnosed as solid masses or lymphadenopathy in imaging studies, due to the variable densities of the cyst contents. More invasive tests, like fine needle aspiration or surgical resection of the bronchogenic cyst, may be necessary when HRCT fails to provide an initial diagnosis. We describe two such cases seen at our institution that highlight the implications of establishing a diagnosis of bronchogenic cyst with endobronchial ultrasound (EBUS) - trans-bronchial needle aspiration (TBNA) and discuss the possible therapeutic utility of EBUS-TBNA in select patients with bronchogenic cysts.

Abbreviation List

BAL - Bronchoalveolar lavage

CNS - Coagulase-negative Staphylococcus

CT – Computed tomography

EBUS - Endobronchial ultrasound

EUS – Endoscopic ultrasound

FOB - Fiberoptic bronchoscopy

HRCT - High resolution computerized tomography

MRI - Magnetic resonance imaging

RUL – Right upper lobe

TBNA - Trans-bronchial needle aspiration

VATS - Video-assisted thoracoscopic surgery

Introduction

Modern imaging, particularly high-resolution computed tomography (HRCT) and magnetic resonance imaging facilitate the evaluation of mediastinal masses. However, definite characterization is possible only after tissue sampling is obtained, typically through fine-needle aspiration or surgical resection. Herein, we report two cases of patients with mediastinal masses, where HRCT failed to provide a diagnosis. Bronchogenic cysts in both patients were ultimately diagnosed by endobronchial ultrasound (EBUS) and trans-bronchial needle aspiration (TBNA). The implications of establishing a diagnosis of bronchogenic cyst via EBUS-TBNA and therapeutic approaches are discussed.

Case 1

A 68-year-old African American woman with hypertension, diabetes mellitus type 2 and end-stage renal disease, on home hemodialysis, presented to the hospital with central stabbing chest pain, radiating to the back, accompanied by shortness of breath. An initial HRCT chest performed to rule out aortic dissection revealed a large subcarinal mass, measuring 2.3 cm x 6.5 cm x 3.8 cm (AP x transverse x height), that splayed the carina, exerting mass effect on the esophagus, raising suspicion of malignancy (Figure 1).

Figure 1. Subcarinal mass. Density ranged from 25-80 Hounsfield Units.

A separate 2.2 cm x 1.7 cm right paratracheal mass, mediastinal lymphadenopathy and many small prevascular lymph nodes were noted. These clinical and imaging findings were concerning for possible lymphoma.

A fiberoptic bronchoscopy (FOB), followed by blind TBNA of the subcarinal space using a Wang needle was attempted. Both, bronchoalveolar lavage (BAL) and TBNA were unrevealing. The patient was found to have persistent coagulase-negative Staphylococcus (CNS) bacteremia, with the first blood cultures being positive at the time of admission. A thorough evaluation, which included an echocardiogram and abdominal HRCT, failed to reveal a source of bacteremia, which was ultimately thought to be related to hemodialysis. Arrangements for outpatient EBUS evaluation of the mediastinal mass and lymphadenopathy were made and the patient was discharged.

A week later, she was readmitted for hypertensive emergency. EBUS was performed during this hospitalization and a cystic mass with heterogeneous-containing material was detected in the subcarinal space (Figure 2).

Figure 2 EBUS image of bronchogenic cyst and adjacent subcarinal lymph node.

The needle aspirate was sent for histological analysis and culture, but it was not possible to drain this cystic structure. Cytopathologic analysis showed bronchial and ciliated cells with abundant mucoid material and a diagnosis of bronchogenic cyst was made. Interestingly, the cultures from the aspirated material grew CNS. The patient was discharged with plans for a video-assisted thoracoscopic surgery (VATS) resection of the bronchogenic cyst as an outpatient.

Five days later, the patient was readmitted with symptoms that were concerning for sepsis, and was thus re-started on broad-spectrum antibiotics. She was found to have Enterobacter intermedius bacteremia. She subsequently underwent VATS, with direct aspiration of the bronchogenic cyst. A resection was not performed due to technical difficulties encountered during VATS. Purulent fluid was retrieved from the cyst and Enterobacter intermedius was identified upon analysis and culture of the cyst content. The patient had no further episodes of bacteremia after eight months of follow-up.

Case 2

A 43-year-old woman without significant past medical history was referred to our institute, for evaluation of a pretracheal lymph node seen on a chest HRCT (Figure 3) done for evaluation of new onset dyspnea and wheezing. Upon auscultation, a localized wheeze was noted with deep inspiration in the right upper chest. Her physical exam was otherwise unremarkable.

Figure 3. Chest CT showing subcarinal lymphadenopathy and mass. Density of mass 9-95 Hounsfield units.

A bronchoscopic exam with EBUS evaluation of lymphadenopathy was scheduled. On FOB, the patient was found to have an incidental endobronchial mass occluding the anterior segment of the right upper lobe. EBUS exam revealed an enlarged subcarinal lymph node (8 mm) with an adjacent cystic space containing homogenous hypoechoic material (Figure 4).

Figure 4. EBUS of bronchogenic cyst. A) Cyst prior to aspiration. B) Collapsed cystic cavity with enlarged lymph node now visible.

Both the lymph node and cystic space were sampled. Ten mL of serous fluid was aspirated from the cystic space, resulting in obliteration of the cavity, as visualized on the ultrasound (Figure 5).

Figure 5.Serous aspirate from cystic cavity.

Full mediastinal staging was done, and only station 11R lymph nodes were found to be enlarged and were sampled. Endobronchial biopsies, brushings and BAL were obtained from RUL endobronchial lesion. The patient was discharged home on empiric antibiotics (amoxicillin/clavulanate) for aspirated bronchogenic cyst. Subsequent fluid analysis revealed abundant macrophages and lymphocytes, consistent with cystic fluid content. Cultures of the fluid were positive for Streptococcus viridians. Lymph node sampling failed to reveal any evidence of malignancy. Interestingly, endobronchial mass biopsies, brushings and fluid cytology also failed to show evidence of malignancy. Only reactive inflammatory cells and benign bronchial elements were detected. The patient was continued on antibiotics for ten days without any evidence of infection.

A repeat bronchoscopy was performed to re-sample the endobronchial lesion. Benign elements were confirmed on the repeat biopsy. Follow up imaging has not been performed to evaluate fluid re-accumulation, since the patient has remained asymptomatic for two months.

Discussion

Mediastinal bronchogenic cysts are congenital anomalies of tracheobronchial origin; they are believed to be a result of an abnormal budding process during the development of foregut. They are often asymptomatic at presentation but can become symptomatic in 30% to 80% of cases due to infection or other complications like compressive efforts (1).

These cysts, being lined by secretary respiratory epithelium, consist of fluid of water density; however, the amount of proteinous mucus and calcium oxalate crystals in them can vary, affecting the imaging features on CT/MRI. A chest CT may reveal spherical masses with water or soft–tissue attenuation. A chest CT may misdiagnose them as soft-tissue masses in about 43% of patients. High attenuation on a chest CT can be a result of calcium oxalate or protein content, or can be due to infection of the cyst content (2, 3).

Due to the variable density in the cyst’s content, bronchogenic cysts can be misdiagnosed as masses or lymphadenopathy on non-invasive testing, as noted in our patients. EBUS can be of great help in diagnosing these lesions. Ultrasound provides an excellent delineation between tissues of different densities, and the absence of flow with color Doppler allows for differentiation from vascular structures. Ultrasonography allows a better delineation of cystic lesions and characterization of their contents (e.g. hypoechoic, isoechoic, heterogeneous, etc.), thereby providing useful diagnostic information. Needle aspiration of cyst contents can bring about not only cytological confirmation of the diagnosis, but also identification of complications such as infected bronchogenic cysts.

Our cases highlight the usefulness of EBUS in the diagnosis of bronchogenic cysts. In the first case, the diagnosis of bronchogenic cyst was made only after EBUS imaging and content aspiration were obtained, despite the initial chest HRCT specifically done to evaluate this mass. In the second case, EBUS imaging established the diagnosis in the absence of any suggestive findings on the HRCT.

The treatment of choice remains the complete surgical resection of the secreting mucosal lining, particularly in complicated cysts (11, 12). However, some authors have reported cases of successful treatment of bronchogenic cysts with EBUS-guided aspiration (4-8). In one case, a patient was followed up for eighteen months without evidence of recurrence (8). The rationale behind this approach is that complete drainage of the cyst obliterates the cyst cavity and prevents further fluid re-accumulation. In our first case, though complete drainage was not achieved with EBUS due to its thick mucoid content, aspiration of the cyst by VATS resulted in resolution without fluid re-accumulation. In our second case, resolution of the cyst was achieved via EBUS-TBNA drainage. These cases underscore the usefulness of aspiration of bronchogenic cysts as an alternative therapeutic approach to surgery in certain scenarios.

Contrary to the above mentioned cases, other case reports have pointed out life-threatening complications after bronchogenic cyst drainage with EBUS-guided FNA, such as pneumonia (9) or purulent pericardial effusion (10). As mentioned elsewhere, empiric antibiotic therapy should be given when a cystic lesion is drained via EBUS-TBNA (13). It should be noted, however, that in some of these case reports, infection post-EBUS-TBNA occurred despite giving empiric antibiotics (9), as in our first case.

The risk of infection should be underscored, as evidenced by the first case; particularly the less frequently reported possibility of bronchogenic cyst infection from bacteremia. The initial EBUS-TBNA cyst aspirate grew CNS, similarly to the blood cultures that were obtained prior to the blind TBNA sample of the mediastinal lesion. This suggests that the contamination of the cyst content could have been due to seeding from CNS bacteremia. However, the final VATS aspirate of the cyst grew Enterecoccus intermedius, which was likely to have been introduced by the EBUS-TBNA at the time of diagnosis. This infection occurred despite the use of antibiotics before and after the procedure. In this regard, the available literature is scant. In a study conducted by Steinfort et al. (14), incidence of bacteremia after EBUS-TBNA was found to be 7%, comparable to reported incidence of bacteremia from regular FOB. It is important to note that although none of these patients experienced clinical signs of infection, none of the biopsies were taken from cystic structures. Data evaluating EBUS-TBNA of mediastinal cystic lesions is conflicting. In a report of 22 patients undergoing EUS-TBNA of suspected mediastinal cyst and receiving periprocedural antibiotics, no infectious complications were found (15). However, several case reports of serious infectious complications after EBUS-TBNA have also been published (16).

Conclusion

Diagnosis of bronchogenic cysts cannot always be made with commonly used chest-imaging modalities such as X-ray or CT. EBUS has proven to be a useful diagnostic tool in the evaluation of some mediastinal masses. Although surgical resection remains the treatment of choice, complete aspiration, by VATS or EBUS, can be a successful therapeutic alternative in patients who are not candidates for surgery. However, the risks should be carefully assessed in each patient, with particular awareness of potential infectious complications. When this approach is taken, empiric antibiotics are recommended.

References

1. St-Georges R, Deslauriers J, Duranceau A, Vaillancourt R, Deschamps C, Beauchamp G, Pagé A, Brisson J. Clinical spectrum of bronchogenic cysts of mediastinum and lung in adult. Ann Thorac Surg. 1991;52:6-13. [CrossRef] [PubMed]
2. Mc Adams HP, Kirejczyk WM, Rosado-de-Christenson ML, Matsumoto S. Bronchogenic cyst: imaging features with clinical and histopathological correlation. Radiology. 2000;217:441-6. [CrossRef] [PubMed] 
3. Patel SR, Meeker DP, Biscotti CV, Kirby TJ, Rice TW. Presentation and management of bronchogenic cysts in adult. Chest 1994;106:79-85. [CrossRef] [PubMed] 
4. Aragaki-Nakahodo AA, Guitron-Roig J, Eschenbacher W, Benzaquen S, Cudzilo C. Endobronchial ultrasound-guided needle aspiration of a bronchogenic cyst to liberate from mechanical ventilation: case report and literature review. J Bronchology Interv Pulmonol. 2013;20(2):152-4. [CrossRef] [PubMed]
5. Meseguer SM, Franco-Serrano J. Drainage of a mediastinal cyst by endobronchial ultrasound-guided needle aspiration. Arch Bronconeumol. 2010;46(4):207-8. [CrossRef]  [PubMed]
6. Dhand S and Krimsky W. Bronchogenic cyst treated by endobronchial ultrasound drainage. Thorax. 2008;63(4):386. [CrossRef] [PubMed]
7. Galluccio G, Lucantoni G. Mediastinal bronchogenic cyst's recurrence treated with EBUS-FNA with a long-term follow-up. Eur J Cardiothoracic Surg. 2006; 29(4):627-9. [CrossRef] [PubMed]
8. Casal RF, Jimenez CA, Mehran RJ, Eapen GA, Ost D, Sarkiss M, Morice RC. Infected mediastinal bronchogenic cyst successfully treated by endobronchial ultrasound-guided fine-needle aspiration. Ann Thorac Surg. 2010; 90(4):e52-3. [CrossRef] [PubMed]
9. Hong G, Song J, Lee KJ, Jeon K, Koh WJ, Suh GY, Chung MP, Kim H, Kwon OJ, Um SW. Bronchogenic cyst rupture and pneumonia after endobronchial ultrasound-guided transbronchial needle aspiration: a case report. Tuberc Respir Dis (Seoul). 2013;74(4):177-80. [CrossRef] [PubMed] 
10. Gamrekeli A, Kalweit G, Schäfer H, Huwer H. Infection of a Bronchogenic cyst after ultrasonography-guided fine needle aspiration. Ann Thorac Surg. 2013;95(6):2154-5. [CrossRef] [PubMed]
11. Cioffi U, Bonavina L, De Simone M, Santambrogio L, Pavoni G, Testori A, Peracchia A. Presentation and surgical management of bronchogenic and esophageal duplication cysts in adults. Chest. 1998;113(6):1492-6. [CrossRef] [PubMed] 
12. Anantham D, Phua GC, Low SY, Koh MS. Role of endobronchial ultrasound in the diagnosis of bronchogenic cysts. Diagn Ther Endosc. 2011, 2011:468237. [CrossRef] [PubMed]
13. Haas AR. Infectious complications from full extension endobronchial ultrasound transbronchial needle aspiration. Eur Respir J. 2009;33(4):935-8. [CrossRef] [PubMed]
14. Steinfort DP, Johnson DF, Irving L.B. Incidence of bacteraemia following endobronchial ultrasound-guided transbronchial needle aspiration. Eur Respir J. 2010:36(1):28-32. [CrossRef] [PubMed] 
15. Fazel A, Moezardalan K, Varadarajulu S, Draganov P, Eloubeidi MA. The utility and the safety of EUS-guided FNA in the evaluation of duplication cysts.GastrointestEndosc. 2005; 62(4):575-80. [CrossRef] [PubMed]
16. Jenssen C, Alvarez-Sánchez M. V., Napoléon B and Faiss S. Diagnostic endoscopic ultrasonography: assessment of safety and prevention of complications. World J Gastroenterol. 2012;18(34):4659–76. [CrossRef] [PubMed]

Reference as: Franco-Elizondo R, Patnaik S, Huang K-H G, Mora J. Role of endobronchial ultrasound in the diagnosis and management of bronchogenic cysts: two case descriptions and literature review. Southwest J Pulm Crit Care. 2014;9(2):115-22. doi: http://dx.doi.org/10.13175/swjpcc096-14 PDF

Azathioprine Associated Acute Respiratory Distress Syndrome: Case Report and Literature Review

Dmitriy Scherbak, D.O.

Ruth Wyckoff, M.D.

Clement Singarajah, M.D.

Phoenix VA Healthcare System

Phoenix, AZ

Abstract

A 58-year-old Caucasian man treated with azathioprine to prevent rejection of an orthotopic liver transplant, presented to the Carl Hayden VA Medical Center with rapid respiratory decline and appeared septic. He required urgent intubation, mechanical ventilator support and empiric antibiotics. His clinical picture and imaging studies were consistent with acute respiratory distress syndrome; however, extensive infectious work up failed to reveal an offending organism. Review of his current medications implicated azathioprine and upon discontinuation of this agent, the patient made a rapid recovery. He was subsequently extubated, transferred out of the ICU and soon discharged home in good health.

Prescribed for organ transplant rejection and a wide array of autoimmune diseases, azathioprine has been rarely correlated with pneumonitis and rapid respiratory failure. No reported cases were found in which azathioprine was used to treat liver transplant rejection and associated with development of the adult respiratory distress syndrome (ARDS). However, there have been ARDS cases in which azathioprine was used for other purposes. We review all the available cases of azathioprine associated ARDS. The patients in these reports had similar clinical symptoms on presentation as our patient: hypoxia, febrile episodes and rapid development of ARDS with no infectious etiology. Most notable is the rapid resolution of ARDS after discontinuation of azathioprine.

Although azathioprine toxicity related respiratory failure is rare, this correlation should still be considered in the differential for immunosuppressed patients presenting with rapid pulmonary decline. Further studies are needed and warranted to better correlate this connection, but it is imperative to recognize that the relationship exists.

Introduction

Since its first use in 1961, azathioprine (a derivative of 6-mercaptopurine) has been used as a steroid sparing immunosuppressive agent in numerous disorders including prevention of graft rejection for solid organ transplantation (1-2). Azathioprine side effects are commonly gastrointestinal complaints such as nausea and vomiting, occurring in ~19% of patients. Laboratory abnormalities such as leukopenia are also common (17%) with thrombocytopenia and anemia being less common (3-4%) (3). Hepatotoxicity has been reported as well. Pulmonary toxicity is not usually noted as a side effect (1). Sixteen cases have been reported in the literature implicating azathioprine with pulmonary toxicity (1-2, 4-12). In 10 of these cases, the patient developed acute respiratory distress syndrome (ARDS) (1,2,6,8,9,11).

Pulmonary infections have been the leading cause of complications in immunosuppressed recipients of solid organs (13). Therefore, when a patient presents with respiratory distress, an abnormal chest x-ray and fevers, such infections are high on the differential, but the possibility of lung injury resulting from the immunosuppressive agent is often overlooked (1). We present a case of azathioprine induced ARDS in a liver transplant recipient and review the available ARDS cases associated with azathioprine use.

Case Report

We present a 58-year-old white man with a past medical history of end-stage liver disease due to hepatitis C cirrhosis and hepatocellular carcinoma who received an orthotopic liver transplant (OLT) 9 months prior to presentation. He was being treated with azathioprine 150mg daily and tacrolimus 1.5 mg daily to prevent rejection. He presented to the emergency department 9 months after his transplant with shortness of breath and increasing hypoxia. He was admitted to the intensive care unit where he developed respiratory failure that night requiring intubation and ventilator support. He had fevers as high as 105.1⁰F. He had pancytopenia with white blood cell count (WBC) 2.3 thousand cells at presentation, hemoglobin (HGB) 9.8 g/dL and platelets (PLT) 119 thousand cells.

Chest x-ray showed bilateral patchy pulmonary infiltrates. CT of the chest was done as well showing bilateral ground glass opacities and diffuse scattered pulmonary consolidations (Figure 1).

Figure 1. Representative images from chest CT with contrast done on admission showing diffuse ground glass opacities and scattered pulmonary consolidations.

Since he was immunosuppressed he was started on empiric antibiotic coverage with vancomycin, levofloxacin, pipercillin/tazobactam, gancyclovir and fluconazole. Trimethoprim-sulfamethoxazole was added on day 2 of hospitalization. A bronchoscopy with bronchial alveolar lavage (BAL) was done prior to antibiotics. Cell count and differential showed 160 white blood cells, 11% segmented neutrophils and 3% eosinophils, the other 86% of cells were pulmonary macrophages/monocytes and reactive respiratory epithelial cells. No organisms or evidence of malignancy were seen. BAL cultures showed no growth on bacterial, viral, acid fast or mycology cultures. Influenza A and B and a pneumocystis smear were also negative. Blood cultures were taken twice during the patient’s hospitalization during febrile episodes and showed no growth both times in two sets of cultures. On day 6 of hospitalization anti-microbial therapy was discontinued.

The patient’s clinical status continued to deteriorate. Chest x-rays continued to show increasing bilateral pulmonary infiltrates (Figure 2).

Figure 2. Chest x-ray at worst (hospital day 8) showing worsening bilateral pulmonary infiltrates.

The diagnosis of acute respiratory distress syndrome (ARDS) was established. His ventilator settings followed the NHLBI ARDS Network protocol, and on day 6 he was even placed in a prone position. On day 7 of hospitalization his white blood cell count dropped to a nadir of 0.5 thousand cells, hemoglobin dropped to 6.5 g/dL and platelets down to 69 thousand cells). Azathioprine was discontinued due to the pancytopenia and due to finding a few case reports in which it was implicated in ARDS. Within 3 days of azathioprine discontinuation (day 10 of hospitalization), the patient’s chest x-rays and pulmonary function had dramatically improved and he was successfully extubated by the fifth day of azathioprine being withdrawn (day 12 of hospitalization). Daily chest x-rays showed continued resolution of infiltrates (Figure 3).

Figure 3. Chest x-ray from hospital day 15 showing dramatic improvement of infiltrates after azathioprine discontinuation.

He improved rapidly and was discharged from the ICU on day 17 and discharged home from the hospital on day 18 with complete resolution of his pulmonary symptoms. His azathioprine was not restarted but he resumed tacrolimus for immunosuppression. Six months after admission, the patient was in good health with no clinical symptoms.

Discussion

Azathioprine is a nitroimidazole derivative of 6-mercaptopurine (4). It was first used in 1961 and has since become a common medication for treatment of numerous auto-immune disorders and as an immunosuppressant in transplant recipients (1). It has been described to have several reversible dose dependent side effects including bone marrow suppression, hepatotoxicity, anorexia, nausea and vomiting (4). Hypersensitivity reactions have also been described and include fevers, rigors, arthralgia, myalgia, cutaneous reactions, headaches, interstitial nephritis, pancreatitis, dyspnea, cough and pneumonitis (1-4, 6).

In our case the patient developed pneumonitis and ARDS which resolved rapidly after the discontinuation of azathioprine. A review of the literature using broad search terms in OVID, Pub-Med and Google Scholar revealed only 10 articles constituting 16 cases of pulmonary toxicity linked to azathioprine. Detailed analysis showed only 5 reported cases of ARDS linked to azathioprine toxicity (2,6,8,9,11), and a single case series of 7 cases of which 2 also have an infectious etiology (1). Data from these cases are summarized on table 1.

Table 1. Cases of Azathioprine induced ARDS in the literature.

The four remaining articles not appearing in table 1 were excluded because they either represented an immediate hypersensitivity reaction to azathioprine or had infectious pneumonitis which could have contributed to the development of ARDS (4,5,10,12).

Neither our case nor those in the literature contain irrefutable proof that azathioprine was directly responsible for lung injury. However, the similarities between the cases in which the patient survived lead us to conclude that azathioprine is involved in this adverse reaction. First, all 8 cases in which the patient survived show a rapid improvement within one to two weeks after discontinuation of azathioprine. Second, all of these patients present in the same way with hypoxia, pulmonary infiltrates, and fevers. Third, none of the cases show any other possible causes and the ones that go to biopsy have non-specific findings (UIP or diffuse alveolar damage) (1,2,6,7,11). These observations are circumstantial, but the diagnosis of drug-induced pulmonary toxicity is usually based on clinical history of drug exposure and the absence of other known causative agents. Additionally, diffuse interstitial pulmonary disease is the most common form of lung pathology caused by drugs (1,14).

Leukopenia or pancytopenia were present in our case as well as 4 of the 10 reported cases (6,8,9,11). No other side effects from azathioprine were reported in any of the cases. Therefore ARDS is likely a unique effect and unrelated to other potential side effects of azathioprine. The dose of azathioprine was widely variable in the known cases (25-150mg daily) leading us to believe that the development of ARDS is not dose-dependent. All of the cases had patients who had been on azathioprine for months (years in one case) prior to developing pneumonitis or ARDS, leading us to speculate that ARDS is not an acute hypersensitivity. It may be that ARDS development is a function of dose effect over time.

Although there are very few reported cases, It is possible that azathioprine induced lung injury is more common than it appears. When an immunosuppressed patient presents with respiratory distress, some form of infectious etiology is usually involved and the immunosuppressants are often discontinued (1). It is possible that in some of these cases azathioprine itself is the cause or may at least contribute to the development of ARDS. We believe it is important that azathioprine lung toxicity be included in the differential for ARDS causes because prompt discontinuation of azathioprine has led to rapid recovery and good outcome in 8 of the 10 known cases (1,2,6,8,9,11).

Acknowledgments

Sarah Waybright, Pharm.D. and Lindsay Kittler, Pharm.D. The clinical pharmacists who noted case reports of azathioprine causing pulmonary toxicity and recommended it’s discontinuation in our patient.

References

1. Bedrossian CW, Sussman J, Conklin RH, Kahan B. Azathioprine-associated interstitial pneumonitis. Am J of Clin Pathol. 1984;82(2):148-54. [PubMed]
2. Weisenburger DD. Interstitial pneumonitis associated with azathioprine therapy. Am J of Clin Pathol. 1978;69(2):181-5. [PubMed]
3. Whisnant JK, Pelkey J. Rheumatoid arthritis: treatment with azathioprine (IMURAN (R)). Clinical side-effects and laboratory abnormalities. Ann Rheum Dis. 1982;41:44-47. [CrossRef] [PubMed]
4. Stetter M, Schmidl M, Krapf R. Azathioprine hypersensitivity mimicking Goodpasture's syndrome. Am J of Kidney Dis. 1994;23(6):874-7. [CrossRef] [PubMed]
5. Krowka MJ, Breuer RI, Kehoe TJ. Azathioprine-associated pulmonary dysfunction. Chest. 1983;83(4):696-8. [CrossRef] [PubMed]
6. Rubin G, Baume P, Vandenberg R. Azathioprine and acute restrictive lung disease. Aust N Z J Med. 1972 Aug;2(3):272-4. [CrossRef] [PubMed]
7. Bidinger JJ, Sky K, Battafarano DF. Henning JS. The cutaneous and systemic manifestations of azathioprine hypersensitivity syndrome. [Review] J Am Acad Dermatol. 2011;65(1):184-91. [CrossRef] [PubMed]
8. Carmichael DJS, Hamilton DV, Evans DB, Stovin PGI, Calne RY. Interstitial pneumonitis secondary to azathioprine in a renal transplant patient. Thorax. 1983;38:951-952. [CrossRef] [PubMed]
9. Perreaux F, Delphine Z, Capron F, Trioche P, Odievre M, Labrune P. Azathioprine-induced lung toxicity and efficacy of cyclosporine a in a young girl with type 2 autoimmune hepatitis. J Ped Gastroenterol Nutr. 2000;31:190-192. [CrossRef]
10. Ananthakrishnan AN, Attila T, Otterson MF, Lipchik RJ, Massey BT, Komorowski RA, Binion DG. Severe pulmonary toxicity after azathioprine/6-mercatopurine initiation for treatment of inflammatory bowel disease. J Clin Gastroenterol. 2007;41(7):682-688. [CrossRef] [PubMed]
11. Brown AL, Corris PA, Ashcroft T, Wilkinson R. Azathioprine-related interstitial pneumonitis in a renal transplant recipient. Nephrol Dial Transplant. 1992;7:362-364. [PubMed]
12. Frost J, Carion G, Mazer J. A case of azathioprine hypersensitivity syndrome, acute respiratory distress syndrome, and shock. Crit Care Med Suppl. 2011;32(12):926.
13. De Gasperi A, Feltracco P, Ceravola E, Mazza E. Pulmonary complications in patients receiving a solid-organ transplant. Curr Opin Crit Care. 2014;20(4):411-419. [CrossRef] [PubMed]
14. Camus P, Fanton A, Bonniaud P, Camus C, Foucher P. Interstitial lung disease induced by drugs and radiation. Respir. 2004;71:01-326. [CrossRef] [PubMed]

Reference as: Scherbak D, Wyckoff R, Singarajah C. Azathioprine associated acute respiratory distress syndrome: case report and literature review. Southwest J Pulm Crit Care. 2014;9(2):94-100. doi: http://dx.doi.org/10.13175/swjpcc087-14 PDF

Wireless Capsule Endo Bronchoscopy

 David M. Baratz, MD

Sandra Till, DO

Banner Good Samaritan Medical Center

Phoenix, AZ

Case Presentation

History of Present Illness

A 67 year-old man presents 10 days after swallowing a capsule endoscopy camera that was never retrieved.  The wireless capsule was swallowed asymptomatically for evaluation of heme positive stools after negative upper and lower endoscopies. Patient noted that the evening after swallowing the camera he developed mild shortness of breath and cough. The cough and shortness of breath were persistent and worsened while lying down and when moving positions. He denied prior issues with swallowing or aspiration.

Review of Systems

Negative other than what is noted above.

PMH, SH, and FH

Past medical history: coronary artery disease, peripheral vascular disease, hyperlipidemia

Surgical history: femoral-popliteal bypass, previous shoulder and back surgery

Social history: 1 pack/day of cigarettes for 50 years, prior alcohol usage but not current, no illicit drugs

Family history: no pulmonary diseases

Physical Exam

Vital signs: temperature 36.7º C, heart rate 86 beats per minute, respiratory rate 15 breaths/min, blood pressure 156/69, and oxygen saturation 97% while breathing  room air

Lungs: bilateral wheezing with left greater than right.

Otherwise examination was normal.

Radiography

The admission chest x-ray is shown in figure 1.

Figure 1. Chest x-ray with capsule in left main bronchus (arrow).

A thoracic CT scan is shown in Figure 2.

Figure 2. Thoracic non-contrast CT scan with capsule in left main bronchus (arrow).

Bronchoscopy was performed under general anesthesia using a laryngeal mask airway (LMA). Bronchoscopic examination revealed a white capsule lodged in left main bronchus (Figure 3).

Figure 3. Bronchoscopy with capsule in left main bronchus.

A mesh basket was used to retrieve of the capsule from the left main bronchus, but in the carina the capsule slipped out of the basket. Attempts to use snare and retrieval forceps failed due to the slippery plastic housing covering the capsule.  The mesh basket was used again with capture of the capsule. Once the capsule was retrieved, the LMA was removed to avoid en bloc damage to the vocal cord while removing the capsule. The LMA was then reinserted for continued ventilation after the capsule had been obtained.

Figure 4. Intact capsule after removal.

Literature Review

Capsule endoscopy has been available since 2001 and is used for the evaluation of obscure gastrointestinal bleeding and iron deficiency anemia. The retention rate is 1-2%, with capsules typically found in diverticula, hernias, or other bowel abnormalities (1-3). It is reported that approximately 2% of patients will have difficulty or inability to swallow the capsule.  Review of 13 available cases of aspiration of wireless endoscopy capsules revealed that about 50% of the time capsules are spontaneously expulsed by coughing, and the other half requiring bronchoscopic intervention for removal (Table 1).

Table 1. Summary of cases with aspirated wireless endoscopy capsules.

Risks for aspiration include underlying neurologic disease, elderly patients, and patient with previous difficulties with swallowing. Signs of capsule aspiration vary from asymptomatic to shortness of breath, cough, and tachypnea (1-12).

The capsule is a wirelesses, 11 mm X 26 mm capsule with a miniature video camera, light emitting diodes, batteries, transmitter, and an antenna. It is slippery, nonbiodegradable, has plastic housing, and weighs less than 4 grams (13).

This case represents a rare, but important complication of wireless capsule endoscopy requiring evaluation and possible intervention. Although this complication is rare, it is likely we will see increasing frequency as capsule utilization increases.

References

1. Guy T, Jouneau S, D'Halluin PN, Lena H. Asymptomatic bronchial aspiration of a video capsule. Interact Cardiovasc Thorac Surg. 2009;8(5):568-70. [CrossRef] [PubMed] 
2. Depriest K, Wahla AS, Blair R, Fein B, Chin R Jr. Capsule endoscopy removal through flexible bronchoscopy. Respiration. 2010;79(5):421-4. [CrossRef] [PubMed] 
3. Koulaouzidis A, Pendlebury J, Douglas S, Plevris JN. Aspiration of video capsule: rare but potentially life-threatening complication to include in your consent form. Am J Gastroenterol. 2009;104(6):1602-3. [CrossRef] [PubMed] 
4. Choi HS, Kim JO, Kim HG, Lee TH, Kim WJ, Cho WY, Cho JY, Lee JS. A case of asymptomatic aspiration of a capsule endoscope with a successful resolution. Gut Liver. 2010;4(1):114-6. [CrossRef] [PubMed]
5. Buchkremer F, Herrmann T, Stremmel W. Mild respiratory distress after wireless capsule endoscopy. Gut. 2004;53(3):472. [CrossRef] [PubMed]
6. Ding NS, Hair C, De Cruz P, Watson J. Education and Imaging. Gastrointestinal: symptomatic bronchial aspiration of capsule endoscope - a significant complication. J Gastroenterol Hepatol. 2013;28(5):761. [CrossRef] [PubMed]
7. Nathan SR, Biernat L. Aspiration--an important complication of small-bowel video capsule endoscopy. Endoscopy. 2007;39 Suppl 1:E343. [CrossRef] [PubMed] 
8. Pezzoli A, Fusetti N, Carella A, Gullini S. Asymptomatic bronchial aspiration and prolonged retention of a capsule endoscope: a case report. J Med Case Rep. 2011;5:341. [CrossRef] [PubMed] 
9. Schneider AR, Hoepffner N, Rösch W, Caspary WF. Aspiration of an M2A capsule. Endoscopy. 2003;35(8):713. [CrossRef] [PubMed] 
10. Bredenoord AJ, Stolk MF, Al-toma A.Tabib S, Fuller C, Daniels J, Lo SK. Unintentional video capsule bronchoscopy. Eur J Gastroenterol Hepatol. 2009;21(5):593. [CrossRef] [PubMed] 
11. Tabib S, Fuller C, Daniels J, Lo SK.Sepehr A, Albers GC, Armstrong WB. Asymptomatic aspiration of a capsule endoscope. Gastrointest Endosc. 2004;60(5):845-8. [CrossRef] [PubMed]
12. Sepehr A, Albers GC, Armstrong WB. Aspiration of a capsule endoscope and description of a unique retrieval technique. Otolaryngol Head Neck Surg. 2007;137(6):965-6. [CrossRef] [PubMed]
13. Kelley SR, Lohr JM. Retained wireless video enteroscopy capsule: a case report and review of the literature. J Surg Educ. 2009;66(5):296-300. [CrossRef] [PubMed]

Reference as: Baratz DM, Till S. Wireless capsule endo bronchoscopy. Southwest J Pulm Crit Care. 2014;8(3):183-7. doi: http://dx.doi.org/10.13175/swjpcc014-14 PDF

December 2013 Pulmonary Case of the Month: Natural Progression

Robert W. Viggiano, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 68 year old woman was seen for increased back pain in April 2012. In 2000 she had a right lower lobe lung resection for low grade adenocarcinoma, bronchoalveolar type, nonmucinous. Her mass was 2.6 cm in maximal dimension extending to but not invading the pleura. There were clear surgical margins but involvement of one bronchial node. Multiple mediastinal nodes were negative. She had back pain for many years and yearly CTs were negative for metastatic disease.

PMH, SH, FH

Other than the above there was no significant past medical history, social history or family history.

Medications

• Non-steroidal anti-inflammatory drugs for pain
• Nitrofurantoin for chronic urinary tract infections

Physical Examination

There was tenderness to palpation over the mid-thoracic spine and evidence of a previous thoracotomy.

Laboratory

Her complete blood count (CBC), urinanalysis, liver function tests, and calcium were all within normal limits.

Radiology

An x-ray of the chest is interpreted as unchanged from previous x-rays. 

At this point which of the following radiologic testing is not indicated?

1. Bone scan
2. CT scan of the chest
3. Magnetic resonance imaging
4. Serial chest x-rays
5. Thoracic PET scan

Reference as: Viggiano RW. December 2013 pulmonary case of the month: natural progression. Southwest J Pulm Crit Care. 2013;7(6): . doi: http://dx.doi.org/10.13175/swjpcc155-13 PDF

December 2013 Pulmonary Case of the Month: Natural Progression

Robert W. Viggiano, MD 

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 68 year old woman was seen for increased back pain in April 2012. In 2000 she had a right lower lobe lung resection for low grade adenocarcinoma, bronchoalveolar type, nonmucinous. Her mass was 2.6 cm in maximal dimension extending to but not invading the pleura. There were clear surgical margins but involvement of one bronchial node. Multiple mediastinal nodes were negative. She had back pain for many years and yearly CTs were negative for metastatic disease.

PMH, SH, FH

Other than the above there was no significant past medical history, social history or family history.

Medications

• Non-steroidal anti-inflammatory drugs for pain 
• Nitrofurantoin for chronic urinary tract infections

Physical Examination

There was tenderness to palpation over the mid-thoracic spine and evidence of a previous thoracotomy.

Laboratory

Her complete blood count (CBC), urinanalysis, liver function tests, and calcium were all within normal limits.

Radiology

An x-ray of the chest is interpreted as unchanged from previous x-rays. 

At this point which of the following radiologic testing is not indicated? (click on correct answer to move to next panel)

1. Bone scan
2. CT scan of the chest
3. Magnetic resonance imaging
4. Serial chest x-rays
5. Thoracic PET scan

Reference as: Viggiano RW. December 2013 pulmonary case of the month: natural progression. Southwest J Pulm Crit Care. 2013;7(6):318-27. doi: http://dx.doi.org/10.13175/swjpcc155-13 PDF