Clinical Significance of Spontaneous Pneumomediastinum

Clinical Significance of Spontaneous Pneumomediastinum

Clinical Significance of Spontaneous Pneumomediastinum Brittany A. Potz, MD, Linda H. Chao, BA, Thomas T. Ng, MD, and Ikenna C. Okereke, MD Department ...

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Clinical Significance of Spontaneous Pneumomediastinum Brittany A. Potz, MD, Linda H. Chao, BA, Thomas T. Ng, MD, and Ikenna C. Okereke, MD Department of Surgery and Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island; and Division of Cardiothoracic Surgery, University of Texas Medical Branch, Galveston, Texas

Background. Spontaneous pneumomediastinum (SPM) is classified as free air in the mediastinum in the absence of any precipitating cause. It is relatively uncommon, and the clinical significance and risk associated with SPM is not well understood and has not been widely documented in the literature. Our goals were to determine the outcomes of patients who presented with SPM and to determine predictors of severe pathology associated with SPM. Methods. From 2004 through 2013, a retrospective review was conducted of patients who presented with SPM to our institution. Patient demographics, comorbidities, laboratory tests, and esophageal perforation were recorded. Results. In all, 249 patients were discovered to have SPM on chest radiograph or computed tomography scan. Mean age was 38.7 years (range, 17 to 81). Sixty-one percent of patients (151 of 249) were male. Ten percent

of all patients (24 of 249) were ultimately discovered to have esophageal perforation, determined by upper endoscopy, upper gastrointestinal series, or intraoperatively during emergent surgery. Age (p < 0.01), pleural effusion (p < 0.01), and elevated white blood cell count (p < 0.01) were the only significant risk factors for esophageal perforation on multivariate analysis. Conclusions. Spontaneous pneumomediastinum is usually associated with a benign clinical course. Risk factors for esophageal perforation in these patients include age, elevated white blood cell count, and a pleural effusion. In the absence of abnormal laboratory values or associated radiologic findings, the majority of patients with SPM may be safely observed without the need for further diagnostic testing.

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are benign, but cases of SPM that are associated with esophageal perforation are often accompanied by severe complications such as mediastinitis and sepsis. These complications can be fatal, and these patients require early identification and intervention to reduce morbidity and improve survival rate [10, 11]. Our goals were to determine the outcomes of patients who presented with SPM and to determine predictors of serious conditions associated with SPM.

pontaneous pneumomediastinum (SPM) is classified as free air in the mediastinum without any traumatic or iatrogenic cause [1, 2]. This condition occurs when a pressure gradient arises between a source of air and the mediastinum. This pressure gradient rises to a high enough level to cause air to enter the mediastinum, leading to the appearance of SPM on radiographic testing. The air that enters the mediastinum can originate from the bronchial tree, the lungs, or the esophagus [3–5]. Spontaneous pneumomediastinum is relatively uncommon, and the clinical significance and risk associated with it is not well understood and has not been widely documented in the literature [6, 7]. The incidence of SPM in the general population ranges from 0.001% to 0.01% [8]. This difference in prevalence is attributed to differences in diagnostic methods among different medical centers [8]. Spontaneous pneumomediastinum often occurs after “triggering events,” such as Valsalva maneuvers, exercise, drugs, asthma, or vomiting [9]. Many cases of SPM Accepted for publication Feb 13, 2017. Presented at the Eleventh Annual Academic Surgical Congress, Jacksonville, FL, Feb 2–4, 2016. Address correspondence to Dr Okereke, Thoracic Surgery, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555; email: [email protected]

Ó 2017 by The Society of Thoracic Surgeons Published by Elsevier Inc.

(Ann Thorac Surg 2017;-:-–-) Ó 2017 by The Society of Thoracic Surgeons

Material and Methods A retrospective comparative study of all cases of SPM diagnosed over a 10-year period was performed. Approval to conduct this research was obtained by the Institutional Review Board. Between January 1, 2004, and December 31, 2013, all patients with who had a diagnosis of SPM were identified and included in the study. All charts were reviewed for demographic data, radiologic studies, diagnostic interventions, and clinical presentation. Spontaneous pneumomediastinum was defined as the radiologic confirmation of air within the mediastinum without any underlying etiology; SPM was excluded in all cases of trauma, recent aerodigestive tract interventions, or recent surgical interventions. The variables assessed were age, sex, vital signs at presentation, hemoptysis, 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2017.02.051

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hematemesis, subcutaneous emphysema on physical examination, history of asthma, pleural effusion on radiographic study, pneumothorax on radiographic study, initial laboratory values, and esophageal perforation. A patient was said to have a pleural effusion if it was noted by the radiologist in any size on any imaging study. All vital signs, laboratory data, and imaging results were obtained within 1 hour of presentation of the patient to our institution.

Statistical Analysis The Mann-Whitney U test was used to compare differences in continuous variables between different groups. Values such as age and white blood count were analyzed as continuous variables in our study. We did not dichotomize these continuous variables in an attempt to create a cutoff value. Owing to the sample size, continuous variables were listed as median values with interquartile ranges. All categoric variables were compared using Fisher’s exact tests. Any variables that were found to be significant on univariate analysis were entered into logistic regression analysis. A variable was considered to be statistically significant at a p value of 0.05 or less.

Results Over the 10-year span of the study, 249 patients who presented to our institution were discovered to have SPM on chest radiography or computed tomography (CT) scan of the chest. Mean age of the entire cohort was 38.7 years (interquartile range, 17 to 81). Sixty-one percent of the patients (151 of 249) were male. Subcutaneous emphysema was appreciated in 16% of patients (39 of 249). Every patient in the study received a chest radiograph. Thirty-eight percent of patients (95 of 249) also had a CT scan performed. The decision to perform a CT scan was individualized for each patient based on severity of symptoms such as pain or shortness of breath, degree of clinical stability, and abnormal laboratory values such as white blood cell count. Thirty-four percent of patients (84 of 249) had an upper gastrointestinal swallow examination performed, also individualized for each patient based on presenting symptoms. Overall, 65 percent of patients (162 of 249) were admitted to the hospital. The decision to admit the patient to the hospital was individualized in each case and was based on symptoms, laboratory values, and vital signs. The outcomes of all patients are shown in Figure 1. Ten percent of patients (24 of 249) were ultimately discovered to have esophageal perforation. Seventeen of the 24 patients with esophageal perforation underwent emergent surgery, with primary repair of the perforation and coverage with a vascularized muscle flap. The remaining 7 patients were treated nonoperatively, with stenting and chest tube drainage of any associated pleural collection. Mean length of stay in the group of patients with esophageal perforation was 12.5 days. Mortality rate was 16.6% (4 of 24). Of all variables tested age (p < 0.01), pleural effusion (p < 0.01), increased white blood cell count (p < 0.01), and hemoptysis (p ¼ 0.02) were

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determined to be significant risk factors for esophageal perforation on univariate analysis (Table 1). These four statistically significant variables were entered into logistic regression multivariate analysis. After multivariate analysis, only age (p < 0.01), pleural effusion (p < 0.01), and increased white blood cell count (p < 0.01) were significantly associated with esophageal perforation (Table 2). Of the 138 patients admitted to the hospital without esophageal perforation, mean length of stay was 2.8 days. Sixty-nine percent of these patients (95 of 138) were discharged 1 day after admission. All patients were seen in follow-up within 2 weeks of admission. All patients were well without recurrent symptoms at the time of follow-up.

Comment Spontaneous pneumomediastinum is usually associated with a benign clinical course, but it can have potentially devastating complications depending on the etiology. This condition often presents with vague and subtle symptoms such as chest pain, dyspnea, and subcutaneous emphysema. In addition to esophageal perforation, the differential diagnosis for these patients includes pericarditis, pneumonia, myocardial infarction, pulmonary embolism, pneumothorax, and gastrointestinal reflux. The etiology of SPM associated with some of these other diagnoses is unknown, but it may be that excessive Valsalva maneuvers from chest pain trigger SPM. An important and difficult diagnosis to rule out is spontaneous esophageal perforation, or Boerhaave’s syndrome (Fig 2). These patients have a reported mortality rate as high as 50%, even with aggressive medical or surgical treatment. Indeed, cases of esophageal perforation that are from spontaneous rupture have a much higher mortality rate (67%) than other etiologies of esophageal perforation, such as iatrogenic causes or trauma [12]. A delay in treatment of more than 24 hours can result in a doubling of the mortality rate. The mortality rate in patients in our study who had esophageal perforation was 16.7% (4 of 24). Given that our rate of mortality was similar or lower than most other series, especially when excluding iatrogenic etiologies, we do not believe that there were significant delays in diagnosis or treatment. Our goals were to determine the outcomes of patients who presented with SPM and to determine predictors of severe pathology (ie, perforated esophagus) associated with SPM. We found that risk factors for esophageal perforation included age, elevated white blood cell count, and a pleural effusion. That suggests that in the absence of abnormal laboratory values or other radiologic findings, the vast majority of patients with SPM may be safely observed without the need for further diagnostic testing. If there are any confounding factors that could affect laboratory values, such as immunocompromised status, these patients may require a heightened degree of suspicion. A patient being treated with immunosuppressive agents, for example, may have serious pathology but not have an elevated white blood cell count. A patient with SPM who is of advanced age, has an elevated white blood

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Fig 1. Outcomes of all 249 patients in the study. As indicated by bold typeface, after multivariate analysis, age (p < 0.01), pleural effusion (p < 0.01), and increased white blood cell count (p < 0.01) were significantly associated with esophageal perforation. (CT ¼ computed tomography; w/ ¼ with; Xray ¼ radiograph.)

cell count, or a pleural effusion should undergo an upper gastrointestinal evaluation, unless hemodynamic instability mandates that the patient goes emergently to the operating room. If a patient has one of these risk factors and the diagnosis of SPM is questionable on chest radiograph, then a CT scan should be obtained. A stable patient without any of these risk factors can be observed. In our study, there was no individual variable, or combination of variables, that would be sensitive for esophageal perforation 100% of the time without having an unduly high false positive rate. As an example, the initial white blood cell count among patients with

esophageal perforation ranged from 5.5/mL to 39.4/mL. But if 5.5/mL were used as a cutoff to identify patients with esophageal perforation, 221 of 245 patients in our study would have been included in the high-risk group. A similar analysis of all patients without esophageal perforation was also unable to identify a useful cutoff value. It appears that the overall clinical picture, emphasizing these particular risk factors, should be used in the evaluation of a patient with SPM. As our study showed, SPM appears to have a more benign course in younger people. There may be an association between SPM and inhalation drug use or

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Table 1. Univariate Analysis, Factors Associated With Esophageal Perforation in Patients With Subcutaneous Emphysema No Perforation (n ¼ 225)

Presenting Variables Age, years Male Heart rate, beats/min Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Oxygen saturation, % Hemoptysis Hematemesis Subcutaneous emphysema History of asthma Pleural effusion Pneumothorax White blood cells 103/mL Hemoglobin, mg/dL Serum creatinine, mg/dL

25.0 136 95.0 127.0 73.0 98.0 4 10 35 31 14 4 10.9 13.9 0.90

(17.6–57.6) (60.4) (78.0–113.5) (113.0–140.0) (65.0–81.0) (96.0–99.0) (1.8) (4.4) (15.5) (13.8) (6.2) (1.8) (8.7–14.2) (12.4–15.2) (0.71–1.10)

Perforation (n ¼ 24) 62.8 15 94.0 139.5 69.0 96.0 3 2 4 1 13 1 18.1 14.5 0.93

(42.0–81.8) (62.5) (68.8–120.0) (108.3–150.0) (63.0–79.5) (94.0–99.5) (12.5) (8.3) (16.7) (4.2) (54.2) (4.2) (14.0–20.2) (12.2–16.0) (0.80–1.10)

p Value <0.01 0.85 0.52 0.37 0.31 0.15 0.02 0.33 0.78 0.33 <0.01 0.40 <0.01 0.74 0.32

Values are median (interquartile range) or n (%).

excessive Valsalva type maneuvers in this younger population [13]. In our study, we found a correlation between advanced age and esophageal perforation in patients with SPM. This correlation is consistent with a study that examined the incidence of Boerhaave’s syndrome at a single institution and found the mean age to be 54 years [14]. A pleural effusion was a risk factor for esophageal perforation in our study and was usually a result of extravasation of intraluminal contents into the pleural cavity. Tachycardia was not a risk factor, possibly because many patients in our study without esophageal perforation were tachycardic. Some literature suggests a correlation between asthma and SPM [4]. We speculated that patients with asthma would be more likely to have a reason for SPM and would be less likely to have esophageal perforation compared with patients in our study without asthma. But we found that asthma had no statistically significant relationship, positively or negatively, to esophageal perforation in patients with SPM. Although asthma may be a risk factor for SPM, it does not seem to affect the rate of development of esophageal rupture. Patients who have esophageal perforation secondary to Boerhaave’s syndrome can present with retrosternal chest pain and subcutaneous emphysema [15]. Chest imaging

often shows subcutaneous emphysema, pleural effusion, pneumomediastinum, and pneumothorax. Laboratory values may show leukocytosis. In our study, hemoptysis was found to be significantly related to esophageal perforation, but it was present in only 3% of patients (7 of 249). Three of these 7 patients had esophageal perforation. Given these very small numbers and that hemoptysis was not significant on multivariate analysis, we are hesitant to assert any meaningful relationship between hemoptysis and esophageal perforation. Although we believe that our findings are useful in the management of patients who present with SPM, we acknowledge some limitations of our study. Our study did not look into the cause of SPM but instead looked at factors on presentation that would correlate with esophageal perforation, as well as the outcomes of the other patients who did not have esophageal perforation. We chose to focus on esophageal perforation because we anticipated that etiology to be the most life-threatening condition associated with SPM. We did not collect any

Table 2. Independent Factors Associated With Esophageal Perforation in Patients Presenting With Subcutaneous Emphysema, by Multiple Logistic Regression Presenting Variable Age Effusion White blood cell count Hemoptysis CI ¼ confidence interval;

p Value <0.01 <0.01 <0.01 0.07 OR ¼ odds ratio.

OR (95% CI) 1.04 5.87 1.21 9.17

(1.01–1.07) (1.66–20.80) (1.10–1.34) (0.82–1.03)

Fig 2. Computed tomography of the chest image showing esophageal perforation. Note the air in the mediastinum and the bilateral pleural effusions.

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data on cases of secondary pneumomediastinum, and we did not collect data on mortality or long-term outcome. In addition, identification of triggering events in our patients was difficult, given the retrospective nature of the chart review. Finally, this is a single-institution study, but we do believe that our results can help to distinguish which cases of SPM are related to potentially fatal situations. In conclusion, the treatment of SPM with benign etiologies includes rest, oxygen therapy, and analgesia. Importantly, patients who have esophageal perforation in the setting of SPM require urgent and aggressive treatment. Our study helps to distinguish between those patients with SPM who can be observed from those who need further diagnostic studies and emergent care. We found that risk factors for esophageal perforation in these patients include age, elevated white blood cell count, and pleural effusion. In the absence of abnormal laboratory values or associated radiologic findings, the majority of patients with SPM may be safely observed without the need for further diagnostic testing. This work was supported in part by NIH/NIGMS Training Grant 2T32 GM065085 to Dr Potz.

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