Failure of chest tube and fibrinolytic treatments in pediatric parapneumonic effusions: a retrospective cohort study

Introduction

Parapneumonic pleural effusions (PPEs) are collections of fluid within the pleural space following pneumonia and are classified as exudative, fibropurulent, or organizational according to their complexity (1). The exudative stage is characterized by simple, clear fluid which thickens to pus with development of loculations in the fibropurulent stage, and finally evolves into a thick rind trapping the lung in the organizational stage (1,2). Once this fluid is purulent, the collections are defined as empyemas which develop in approximately 28–45% of pediatric patients with pneumonia (1,3). Imaging modalities including ultrasound, chest radiographs, and computed tomography (CT) are used for diagnosis and characterization of these effusions.

Pediatric patients have protective physiology with rapid tissue regeneration allowing up to 52% of parapneumonic effusions or empyemas to be managed with antibiotic therapy alone (4,5). However, 45–82% of pediatric patients with empyemas eventually require drainage procedures (6,7). Intervention options for fluid drainage include thoracentesis, chest tube placement, video-assisted thoracoscopic surgery (VATS), and open thoracotomy. Patient clinical status, effusion size, and presence or absence of loculations influence intervention selection (1). Empyemas are typically initially managed with chest tube placement with the addition of intrapleural fibrinolytic therapy such as dornase or tissue plasminogen activator (tPA) in cases involving complex or loculated collections (1). If the patient fails to improve clinically following initial management with chest tube placement, a step-up approach is often employed with less invasive second chest tube placement or additional fibrinolytic therapy (1). Operative interventions such as VATS or thoracotomy are generally reserved for patients refractory to less invasive treatment.

In adult patients, the American Association for Thoracic Surgery recommends VATS as the first line approach for stage II (fibropurulent) and III (organizational) acute empyema (8). Alternatively, recommendations for pediatric patients with parapneumonic effusions are broad, and management is highly institution dependent with studies highlighting the lack of consensus among pediatric medicine and interventional radiology providers (9). The American Pediatric Surgery Association currently recommends initial chest tube placement with adjunctive fibrinolytic therapy (1). Studies in adult patients on early VATS have shown improved primary outcomes with decreased length of stay and mortality, but the optimal timing of more invasive intervention in pediatric patients is unknown due to their resilience and physiology (4,10-12). Additionally, recent studies on pediatric patients have only shown mechanical ventilation to be associated with need for secondary intervention (13). Further studies are needed to identify predictors of primary intervention failure to guide consideration of secondary intervention in order to expedite recovery. Our aim is to identify predictors of chest tube and fibrinolytic failure in the management of pediatric empyema leading to secondary interventions at our institution to add an additional perspective to the current literature on pediatric empyemas. We present this article in accordance with the STROBE reporting checklist (available at https://pm.amegroups.com/article/view/10.21037/pm-25-43/rc).

Methods

A retrospective single-institution review was conducted of patients 18 years old and younger who underwent chest tube placement for PPEs from January 1, 2019 to December 31, 2023. Patients undergoing chest tube placement were identified by International Classification of Diseases (ICD)-10 codes J91.8 and ICD J86.9 as well as Current Procedural Terminology (CPT) codes 32551, 32556, 32557, 32561, and 32607. Only patients undergoing isolated index chest tube placement for PPEs were included. Patients with chest tube placements for other pathologies such as pneumothoraces, congenital diaphragmatic hernias, or pulmonary resections were excluded.

Initial presentation was evaluated including duration of symptoms prior to hospitalization, symptoms on admission, initial oxygen requirements, white blood cell (WBC) and C-reactive protein (CRP), imaging modalities and findings, antibiotics prior to admission, and total antibiotic duration. Duration of symptoms prior to admission was calculated based on documented date of symptom onset reported by the patient or their parents. Imaging modalities included chest ultrasound, chest X-ray, or CT scans and findings assessed were effusion, loculated effusion, consolidation, opacification, or abscess. Primary interventions were then evaluated including timing of chest tube placement, chest tube size, pleural fluid characteristics and cultures, and timing and duration of fibrinolytic therapy. Hospital course was analyzed with antibiotic duration, oxygen requirements and days requiring supplemental oxygen, and complications. Secondary interventions were then evaluated including procedure performed, additional fibrinolytic therapy days, chest tube duration, and antibiotic duration. Fibrinolytic therapy is dosed once per day, therefore patients who received more than 3 doses of fibrinolytic therapy were considered to have additional fibrinolytic therapy. Primary outcomes were duration of initial chest tube and length of stay. Factors evaluated for prediction of initial intervention failure included duration of symptoms prior to admission, oxygen requirement on admission, infectious laboratory values, initial chest tube duration, and duration of fibrinolytic therapy.

Statistical analysis

Descriptive statistics were used to summarize the data, and bivariate associations of covariates were tested using Chi-squared or Fisher’s exact tests. Categorical variables were summarized with frequencies and proportions, normally distributed data was summarized with mean and standard deviation, and skewed variables were summarized with median and interquartile range. Differences in continuous variables between children requiring VATS versus those not were examined using t-tests or Mann-Whitney U statistics. SAS Analyrtics software was used for data analysis.

Ethical considerations

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by institutional review board of University of Oklahoma (IRB#17280) and individual consent for this retrospective analysis was waived.

Results

We identified 192 patients 18 years and younger who underwent chest tube placement during the 5-year study period. Pediatric cardiothoracic surgery performed 23 of the procedures which were excluded from analysis as they were not for the treatment of empyemas, while pediatric surgery performed 169 of the procedures. Of the chest tubes placed by pediatric surgery, 43 were for parapneumonic effusions and 126 were for other indications including pneumothoraces, pulmonary resections, or congenital diaphragmatic hernia repairs. An outline of how we arrived at our study population is depicted in Figure 1. Our cohorts were based on management with primary or secondary interventions, and patient distribution within these cohorts is also outlined in Figure 1. The primary intervention cohort was comprised of 23 patients who underwent single chest tube placement, with 16 of these patients also receiving fibrinolytic therapy. The secondary intervention cohort included 20 patients who underwent chest tube and fibrinolytic therapy followed by additional fibrinolytic therapy, second chest tube placement, or VATS.

Figure 1 Patient distribution. Description of how patients were identified and distribution of included patients into cohorts based on intervention. VATS, video-assisted thoracoscopic surgery.

On initial presentation, patients in the secondary intervention cohort had significantly longer duration of symptoms prior to presentation (P=0.02), but similar rates of antibiotics prescribed prior to admission (P=0.19). Distribution of imaging modality choice with ultrasound, chest X-ray, or CT scan was comparable across cohorts (P=0.76, 0.29, 0.76). Imaging described effusions with or without loculations, consolidations, and opacifications with no significant differences across cohorts (P=0.25, 0.56, >0.99, 0.23). Patients requiring secondary intervention were also more likely to require oxygen at time of admission (P=0.053). No differences were observed in initial WBC and CRP across cohorts, however values were elevated in both cohorts (P=0.11, 0.35) (Table 1).

Initial intervention was defined as index chest tube placement with or without tPA administration. Descriptions of pleural fluid in operative notes at the time of index chest tube placement revealed that the majority of patients across both cohorts had serous or serosanguinous fluid. Cultures performed on fluid at index chest tube placement were predominantly sterile, with only six cases in each cohort having growth of streptococcus pneumonia, group A streptococcus, or other bacteria which included staphylococcus species, fusobacterium, and parvimonas (Figure 2).

Figure 2 Pleural fluid. (A) Pleural fluid characteristics at time of initial chest tube placement. (B) Pleural fluid cultures at time of initial chest tube placement.

Patients who required secondary intervention had a significantly longer duration of index chest tube prior to undergoing their secondary intervention (P=0.002). These patients also required oxygen supplementation for more days and had greater total duration of antibiotics (P=0.002, P=0.008). A review of operative notes for patients undergoing VATS revealed findings including loculated fluid collections, trapped lungs, and bronchopleural fistulas. Pleural fluid cultures were only available for 8 of the patients in the secondary intervention cohort, however, 6 of those cultures demonstrated no growth. Overall, length of stay was significantly longer for the secondary intervention cohort (P<0.001) (Table 1).

Discussion

Primary intervention for pediatric parapneumonic effusions at our institution has a failure rate of approximately 46.5% leading to additional fibrinolytic therapy, second chest tube placement, or VATS. This is notably higher than other similar studies which estimate a 6% failure rate (14). When presenting to the hospital, patients requiring secondary intervention had longer duration of symptoms prior to admission and often required oxygen on arrival, suggesting more advanced disease process at time of initial intervention. Despite varying timing of disease process between cohorts, no significant differences were observed in imaging findings, infectious laboratory markers, or pleural fluid characteristics at the time of admission or index chest tube placement. The majority of fluid collections were also sterile with few cultures demonstrating bacterial growth.

Patients who failed initial therapy and required additional pleural drainage procedures as secondary interventions were found to have longer duration of index chest tube, highlighting the importance of early consideration of secondary intervention in appropriate cases. Our institution’s protocol includes three days of fibrinolytic therapy with tPA instilled in the chest tube followed by a period of clamping prior to draining fluid. This protocol and our cohort delineation is reflected in the median of 3 days of initial tPA for the primary intervention cohort and 3.5 days for the secondary intervention cohort. Duration of initial chest tube is not an independent predictor of failure, however, it highlights potential delays in care when deciding to proceed with secondary intervention. Patients with successful primary interventions had their index chest tube for a median of 7 days, suggesting assessment and evaluation for possible secondary intervention by day 7 may be warranted. Clinical outcomes for those undergoing secondary interventions, including more days of supplemental oxygen and longer duration of antibiotics, were generally consistent with the increased severity of disease.

Secondary interventions included additional doses of tPA, second chest tube placement, or VATS. Distribution of pleural fluid characteristics at the time of secondary intervention was similar to what was observed for primary intervention. Primary indications for VATS are trapped lung, loculations, necrosis, or failure of clinical improvement, and our operative findings demonstrated high rates of trapped lungs and loculated effusions, supporting the progression to this intervention. Consistent with primary intervention findings, the majority of the available pleural fluid cultures for this cohort showed no bacterial growth. Overall, patients requiring more interventions with more advanced disease processes had longer length of stay which is anticipated.

It is important to note this study is limited as a single-institution review and may not be generalizable to all centers, partly due to bias towards our facility’s standard practice of the management of empyemas. Retrospective chart review also carries bias as information is dependent on provider documentation. Patients included in this study were managed by five different attending physicians allowing for some variation in provider preference to be captured. However, the observed associations should be interpreted with caution as they are representative of a single institution.

Conclusions

Our study demonstrates the association of duration of symptoms and clinical disease severity with failure of primary intervention for parapneumonic effusions in pediatric patients. However, no trends were identified in lab values, pleural fluid characteristics, or pleural fluid cultures as predictors of failure. These findings provide valuable insights into the management of pediatric empyemas and support earlier consideration of secondary intervention in patients presenting with further disease progression to potentially expedite clinical improvement and reduce overall length of stay. This provides the foundation for a larger, prospective or multi-institutional study on the timing of additional pleural drainage or VATS in pediatric empyemas.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://pm.amegroups.com/article/view/10.21037/pm-25-43/rc

Data Sharing Statement: Available at https://pm.amegroups.com/article/view/10.21037/pm-25-43/dss

Peer Review File: Available at https://pm.amegroups.com/article/view/10.21037/pm-25-43/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://pm.amegroups.com/article/view/10.21037/pm-25-43/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by institutional review board of University of Oklahoma (IRB#17280) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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