
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

MD-D-24-04249
00041
10.1097/MD.0000000000039693
3
6700
Research Article
Observational Study
The role of corticosteroids in preventing invasive procedures in patients with parapneumonic effusion in the exudative phase: An observational study
https://orcid.org/0009-0005-3364-9716
Kirac Ali MD a*
Satici Celal a
Erinc Aysegul MD draysgul@hotmail.com
a
Kosar Filiz a
a Department of Pulmonology, Yedikule Chest Disease and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey.
* Correspondence: Ali Kiraç, Department of Pulmonology, Yedikule Chest Disease and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey (e-mail: dralikirac@yahoo.com).
13 9 2024
13 9 2024
103 37 e3969319 4 2024
16 8 2024
23 8 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

The aim of the study was investigate the effect of corticosteroid use on the need for invasive procedure like tube thoracostomy with underwater seal drainage (TT-UWSD) and Video Assisted Thoracoscopic Surgery (VATS) in adult patients diagnosed with parapneumonic effussion in the exudative phase. A retrospective cohort study was performed in a chest diseases hospital. A total of 65 patients were included in the study. While 30 patients received only medical treatment, 35 patients underwent invasive procedures. Data on characteristics, vital signs, and laboratory parameters were recorded from electronic medical records. Univariate and multivariate logistic regression analyses were performed to identify corticosteroid and other predictors of the need for invasive procedures. The outcomes of the multivariate regression analysis revealed that an longer duration of symptoms (OR = 1.10, 95% CI: 1.01–1.21, P < .033) and the presence of dyspnea (OR = 5.44, 95% CI: 1.26–23.50, P < .023) independently associated with an increased need for invasive procedures, while corticosteroid treatment (OR = 0.15, 95% CI: 0.02–0.81, P < .028) was observed to be associated with a reduced necessity for invasive procedures. Treatment with metilprednisolone, together with the absence of dyspnea and shorter symptom duration may independently decrease the need for invasive procedure in patients with parapneumonic pleural effusion in the exudative phase.

corticosteroids
exudative phase
parapneumonic effusion
tube thoracostomy
OPEN-ACCESSTRUE
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pmc1. Introduction

Parapneumonic effusion (PPE) is a fluid that forms in the pleural cavity, caused by pneumonia. PPE accounts for about one-third of all pleural fluids.[1] As the disease progresses, pleural fluid becomes more complicated, and both the need for invasive intervention and the rates of morbidity and mortality increase. Generally, about 15% to 20% of pleural infections have a fatal course and this rate reaches 35% in immunosuppressed patients.[2] In 10% of patients developing parapneumonic effusion, an invasive procedure is required in addition to medical treatment.[3] About 30% of patients undergoing pleural fluid drainage also need surgery.[4]

The development of PPE occurs in 3 stages, and treatment approaches differ at each stage. In the simple exudative phase, the formation of pleural fluid is a result of increased permeability in the neighboring visceral pleura due to inflammation in the lung parenchyma. Complete resolution usually occurs with medical treatment. If bacteria translocate to the pleural space, the fluid starts to become complicated, and this stage is called the fibrinopurulent stage. When the pleural infection progresses to the chronic phase, thickening of fibrin matrix and collagen occurs due to fibroblast proliferation which is called the organized stage.[5,6] In fibrinopurulent and organized parapneumonic effusion, pleural fluid drainage is the mainstay of the management.[7] In pleural fluids with excessive loculations, surgical intervention is necessary if adequate drainage cannot be achieved.[8]

Although invasive procedures including tube thoracostomy and Video Assisted Thoracoscopic Surgery (VATS) are known as definitive treatments, they are associated with higher complications such as re-expansion pulmonary edema, subcutaneous emphysema, nerve injury, cardiovascular injuries, residual pneumothorax, esophageal perforation, fistula, chylothorax, and infection.[9] With this regard, noninvasive management of these patients is crucial in the exudative stage.

In patients diagnosed with PPE in the exudative phase, inflammation is prominent, the role of corticosteroids were inconsistent across the limited number of previous studies. In a randomized double-blind study, the use of dexamethasone was investigated in 60 pediatric patients with PPE; while the recovery period was found to be shorter in patients receiving steroids, there was no significant difference in treatment response and treatment-related complications.[10] In another study conducted in 2021, corticosteroids were used in pediatric patients hospitalized for PPE for the management of persistent fever; while a benefit was observed in reducing the fever, no significant difference was found in the length of hospital stay.[11] In a randomized controlled pilot study (STOPPE study), the use of dexamethasone was compared with placebo in 80 adult patients with parapneumonic effusion. No significant difference was observed in terms of laboratory values, average duration of antibiotic use, and side effects related to corticosteroids.[12] Consequently, a definitive conclusion regarding the availability and efficacy of corticosteroids could not be ascertained. This underscores the necessity to conduct a more comprehensive investigation into the effectiveness of corticosteroids, particularly within distinct disease subgroups. Notably, the study encompassed a range of patients, including those diagnosed with both complicated parapneumonic effusion and those in the exudative phase of PPE. Thus, further investigation within these subgroups is warranted to attain more conclusive insights.[12] In addition, only dexamethasone was used as a corticosteroid in adult patients in these studies, and no data were found regarding the effectiveness of methylprednisolone.

In light of these data, we aimed to investigate the effect of corticosteroid use on the need for invasive procedure in adult patients diagnosed with PPE in the exudative phase who admitted to our hospital.

2. Materials and methods

2.1. Study design and setting

Our study, designed as a retrospective cohort, was conducted at the Yedikule Chest Diseases And Thoracic Surgery Training And Research Hospital. At our institution, a tertiary referral center of pulmonary diseases, a yearly caseload of approximately 1850 patients having a diagnosis of pleural effusion receives ongoing medical oversight. Among these cases, an average of 600 patients undergo the procedure of tube thoracostomy, while a subset of approximately 40 patients necessitates VATS.

Our study was conducted in line with the Declaration of Helsinki. The local institutional ethics committee approved the study protocol (ethics approval number: 2022_207) and waived the requirement for written informed consent due to the retrospective design.

2.2. Study population

During the period spanning from January 1, 2021, to December 31, 2022, a retrospective examination encompassed a cohort of 1413 patients who sought care at our institution with a diagnosis of PPE. The exclusion criteria encompassed patients who had been on a corticosteroid regimen for over 1 month, allowing for the assessment of the acute impact of corticosteroids.[13] We have excluded the patients diagnosed with collagen vascular disease (Rheumatoid arthritis), pulmonary embolism and acute pancreatitis which also cause exudative stage parapneumonic effusion. A total of 278 patients were excluded due to tuberculosis, while 316 patients were excluded on account of malignancies. Furthermore, 330 patients were not included to the study due to their diagnoses of fibrinopurulent and organized pleural effusion, while 210 patients with transudative pleural effusion were likewise not included. An additional 178 patients to whom thoracentesis was not performed due to factors such as insufficient pleural fluid volume (below 10 mm), concurrent anticoagulant usage, a platelet count <50,000, and an INR exceeding 1.5. The remaining 36 patients were also excluded owing to undetermined diagnoses. Within this framework, a subset of 65 patients, aged 18 years and older, characterized by thoracentesis-confirmed exudative phase parapneumonic effusion, were incorporated into the study cohort (Fig. 1).

Figure 1. Flow chart.

2.3. Data collection

Demographic parameters such as age and gender, along with existing comorbidities including hypertension, diabetes mellitus, chronic obstructive pulmonary disease, ischemic heart disease, and congestive heart failure, were documented through extraction from the hospital’s electronic medical records. Presenting clinical symptoms, encompassing dyspnea, cough, chest pain, side pain, fever, and back pain, were likewise acquired. Initial laboratory parameters and pleural fluid parameters (at first admission), were also documented. The administration of antibiotics, encompassing agents such as amoxicillin-clavulanate, third-generation cephalosporins, quinolones, and clindamycin, was systematically noted. Additionally, the utilization of corticosteroids was also documented.

Subsequently, the requirement for interventions such as tube thoracostomy with underwater seal drainage (TT-UWSD) and VATS was meticulously ascertained for each patient and documented accordingly.

2.4. Definitions

Patients who were administered methylprednisolone treatment, regardless of indication, at the time of diagnosis were included within the cohort designated as those receiving corticosteroid treatment in our study. Individuals who underwent TT-UWSD during the course of treatment, as well as those subjected to VATS were encompassed within the category of patients who were performed invasive procedures.

The categorization of pleural fluid was conducted in accordance with Light criteria. The criteria included a protein-to-serum ratio in pleural fluid >0.5, a ratio of lactate dehydrogenase in pleural fluid to lactate dehydrogenase in serum >0.6, and a lactate dehydrogenase value in pleural fluid exceeding two-thirds of the upper limit of the standard laboratory reference value for lactate dehydrogenase in serum. The presence of any 1 of these criteria indicated an exudative nature of the pleural fluid. Additionally, the criteria that pleural fluid lactate dehydrogenase value lower than threefold of the serum counterpart, pleural fluid glucose concentration exceeding 60 mg/dL, and pleural fluid pH surpassing 7.2 were used to discriminate the pleural effusion in exudative phase than those with more complicated course.[14] In alignment with the guideline, medical treatment was tailored accordingly. Patients diagnosed with community-acquired parapneumonic effusion received initial treatment involving amoxicillin-clavulanic acid or a third-generation cephalosporin, in conjunction with clindamycin or metronidazole.[15] For patients who exhibited inadequate improvement within 2 to 3 weeks of antibiotic therapy, displayed pleural fluid loculations during monitoring, or progressed to the fibrinopurulent-organized stage, TT + UWSD was performed. VATS procedure was performed for patients who failed to attain satisfactory amelioration after the initial week of chest tube drainage, antibiotic and fibrinolytic interventions. VATS was also indicated in cases involving pleural space adhesions, impediments to lung expansion due to visceral pleura thickening, and instances necessitating pleurectomy due to substantial pleural surface adhesions and thickening.

2.5. Outcomes

The primary endpoint of our study is to determine whether patients treated for parapneumonic effusion in the exudative phase who received corticosteroid treatment had a lower need for invasive procedures compared to those who did not receive corticosteroid treatment. The secondary endpoint was defined as identifying independent predictors for the need for invasive procedures in patients diagnosed with parapneumonic effusion in the exudative phase.

2.6. Data analysis and statistical methods

We used descriptive statistics to present our data. Categorical data were reported as proportions and numbers; continuous data were presented as mean and standard deviation, median and interquartile range (IQR) was reported unless the data were normally distributed. For the comparison of patients receiving and not receiving steroid treatment; categorical data were analyzed with chi-square analysis, normally distributed continuous variables with the Student t test, otherwise with the Mann–Whitney U test. Parameters found to be statistically significant at a level of P < .20 or thought to be clinically significant in univariate analysis were included in logistic regression analysis. Correlations between continuous variables included in multivariate analysis were examined, and only the parameter considered to be clinically more meaningful was included in the analysis if there was a high correlation (R > 0.8) between variables. The goodness of fit of the model in logistic regression analysis was evaluated with the Hosmer Lemeshow test. Accordingly, the model was accepted as fit if the Hosmer Lemeshow test result was P > .05. For the independent predictors of the requirement to invasive procedures, a ROC analysis was performed and Youden index was used to detect cutoff level. The area under the ROC curve (AUC) of the independent continuous variable predicting invasive interventions was calculated. Considering this cutoff level, two-by-two table analysis was performed to reveal sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and accuracy. A P-value < .05 was considered statistically significant. Analyses were calculated using IBM SPSS Statistics 23.

3. Results

A total of 65 patients, 29% of whom were female, with a mean age of 52.6 ± 17.4 years were included in the study. Twenty-two patients (33.8%) exhibited at least 1 comorbidity. Hypertension (20%) emerged as the most prevalent comorbidity, followed by diabetes mellitus (12.3%), ischemic heart disease (9.2%) and chronic obstructive pulmonary disease (6.2%). Among the noted clinical symptoms, dyspnea was the most frequently reported (46.2%), followed by side pain (41.5%), and cough (27.7%). All patients were diagnosed with community-acquired parapneumonic effusion.

Seventeen patients (26.1%) formed the group who administered corticosteroid treatment. There was no statistically significant difference between groups in terms of age, comorbidities, symptoms, pleural effusion size and laboratory findings (P > .05). However, male predominance was observed within the corticosteroid-treated group (P = .004), along with a tendency towards advanced age (P = .019). Patients in the corticosteroid treatment group were more likely to have COPD (P < .004) and longer duration of symptoms to admission (P < .001). Notably, pleural fluid albumin level was found to be significantly lower (P = .026), while pleural fluid lactate dehydrogenase (LDH) level was observed to be significantly higher (P = .043) in patients subjected to corticosteroid treatment (Table 1). The median duration of corticosteroid treatment was 1 (range: 1–3) day.

Table 1 Demographic, clinic and laboratory parameters.

Variables	Total patients (n = 65)	Corticosteroid treatment (+) (n = 17)	Corticosteroid treatment (−) (n = 48)	P value	
Age, yr (mean ± SD)	52.68 ± 17.45	61.35 ± 16.62	49.60 ± 16.84	.019	
Female gender, n (%)	19 (29)	2 (11.8)	17 (35.4)	.004	
Smoking, n (%)	40 (61)	11 (64)	29 (60)	.755	
Comorbidities, n (%)	
 At least 1 comorbidity	22 (33)	8 (47)	14 (29)	.180	
 Hypertension	13 (20)	5 (29.4)	8 (16.7)	.438	
 Asthma	1 (1.5)	0 (0)	1 (2.1)	.549	
 COPD	4 (6.2)	4 (23.5)	0 (0)	.004	
 Diabetes	8 (12.3)	3 (17.6)	5 (10.4)	.421	
 Ischemic heart disease	6 (9.2)	3 (17.6)	3 (6.3)	.179	
 Rheumatoid arthritis	2 (3.1)	1 (5.9)	1 (2.1)	.436	
 Pulmonary embolism	1 (1.5)	0 (0)	1 (2.1)	.549	
 Heart failure	2 (3.1)	0 (0)	2 (4.2)	.393	
Symptom duration, median (IQR)	10 (7–15)	14 (8.5–20)	7.5 (5.5–14.75)	<.001	
Symptoms, n (%)	
 Dyspnea	30 (46.2)	8 (47.1)	22 (45.8)	.931	
 Fever	12 (18.5)	3 (17.6)	9 (18.8)	1.000	
 Cough	18 (27.7)	3 (17.6)	15 (31.3)	.357	
 Side pain	27 (41.5)	7 (41.2)	20 (41.7)	.972	
 Back pain	12 (18.5)	5 (29.4)	7 (14.6)	.273	
 Chest pain	5 (7.7)	1 (5.9)	4 (8.3)	1.000	
Laboratory values [median (IQR)]	
 Leukocytes (cells/ mm3)*	11.70 ± 4.80	12.55 ± 5.72	11.42 ± 4.46	.543	
 Albumin (g/dL)*	3.62 ± 0.52	3.45 ± 0.50	3.68 ± 0.51	.135	
 CRP (mg/L)*	115.06 ± 107.10	138.6 ± 126.3	107.5 ± 100.1	.186	
 Protein (g/L)	75 (68–79)	73 (68–81)	75 (68–79)	.883	
 Glucose (mg/dL)	110 (97–133)	118 (107–139)	107 (97–132)	.224	
 Lactate dehydrogenase (U/L)	225 (184–296)	262 (224–318)	210 (179–283)	.077	
 Procalcitonin (ng/ml)	0.08 (0.05–0.54)	0.09 (0.06–0.37)	0.08 (0.03–0.64)	.962	
Pleural fluid [median (IQR)]	
 Size (mm)	40 (28.5–55)	50 (37.5–57.5)	37 (25–50)	.135	
 pH*	7.52 ± 0.14	7.51 ± 0.15	7.52 ± 0.14	.873	
 Adenosine deaminase (U/L)	15 (9.75–25.00)	21 (12.40–43.25)	13 (9.70–25.00)	.076	
 Protein (g/L)	51 (45.5–54.5)	50 (45–53)	51 (45.2–54.7)	.805	
 Albumin (g/dL)	2.90 (2.50–3.20)	2.60 (2.25–2.95)	2.90 (2.70–3.20)	.026	
 Lactate dehydrogenase (U/L)	353 (228–552)	471 (256–797)	309 (214–502)	.043	
 Glucose (mg/dL)	106 (93–120)	112 (92–129)	106 (92–117)	.591	
Abbreviations: COPD = chronic obstructive pulmonary disease, CRP = C-reactive protein, IQR = interquartile range, pH = potential of hydrogen.

* Stands for normally distributed parameters and expressed as mean ± standard deviation.

A subset of 30 patients received only medical treatment, whereas 35 patients underwent invasive procedures. Regarding the comparative analysis of these groups, no statistically significant differences were detected in terms of age, smoking status, comorbidities, laboratory values, pleural effusion size or the utilization of corticosteroids (P > .05). Remarkably, a reduced necessity for invasive procedures was evident in female patients (P = .04). Notably, lower pleural fluid pH values were related with an increased requirement for invasive procedures (P = .009). (Table 2). Parameters demonstrating significance (P < .2) in univariate analysis, encompassing gender (P = .004), duration of symptoms (P = .103), dyspnea as a presenting complaint (P = .055), CRP values (P = .089), pleural effusion size (P = .067) pleural fluid pH values (P = .009), pleural fluid LDH values (P = .132), and clinically relevant corticosteroid utilization were included into subsequent multivariate regression analysis.

Table 2 Comparison of the characteristics of patients with and without invasive drainage need.

Variables	Medical treatment (n = 30)	Invasive procedure (n = 35)	P value	
Age, yr (mean ± SD)	53.03 ± 16.32	52.37 ± 18.59	.880	
Female gender, n (%)	14 (46.7)	5 (14.3)	.004	
Smoking, n (%)	17 (56.7)	23 (65.7)	.455	
Comorbidities, n (%)	
 At least 1 comorbidity	9 (30)	13 (37)	.544	
 Hypertension	5 (16.7)	8 (22.9)	.534	
 Asthma	0 (0)	1 (2.9)	1.0	
 COPD	2 (6.7)	2 (5.7)	1.0	
 Diabetes	4 (13.3)	4 (11.4)	1.0	
 Ischemic heart disease	1 (3.3)	5 (14.3)	.205	
 Rheumatoid arthritis	1 (3.3)	1 (2.9)	1.0	
 Pulmonary embolism	1 (3.3)	0 (0)	.462	
 Heart failure	1 (3.3)	1 (2.9)	1.0	
Symptom duration (d), median (IQR)	7.5 (7.0–12.5)	14 (7–21)	.103	
Symptoms, n (%)	
 Dyspnea	10 (33.3)	20 (57.1)	.055	
 Fever	3 (10)	9 (25.7)	.104	
 Cough	9 (30)	9 (25.7)	.700	
 Side pain	16 (53.3)	11 (31.4)	.074	
 Back pain	3 (10)	9 (25.7)	.104	
 Chest pain	2 (6.7)	3 (8.6)	1.0	
Laboratory values [median (IQR)]	
 Leukocytes (cells/mm3)*	11.09 ± 2.95	12.25 ± 5.95	.248	
 Albumin (g/dL)*	3.58 ± 0.49	3.66 ± 0.54	.449	
 CRP (mg/L)*	89.31 ± 72.60	138.41 ± 126.35	.089	
 Procalcitonin (ng/mL)	0.07 (0.04–0.22)	0.18 (0.06–0.56)	.460	
 Lactate dehydrogenase (U/L)	224 (184–308)	225 (182–265)	.961	
 Protein (g/L)	77 (68–82)	73 (68–77)	.151	
 Glucose (mg/dL)	111 (99–129)	109 (97–133)	.989	
Pleural fluid [median (IQR)]	
 Size (mm)	31.5 (25–55)	45 (35–60)	.067	
 pH*	7.57 ± 0.15	7.48 ± 0.13	.009	
 Adenosine deaminase (U/L)	15 (9–26)	16 (8–25)	.819	
 Protein (g/L)	50 (46–56)	51 (45–54)	.410	
 Albumin (g/dL)	2.8 (2.5–3.2)	2.9 (2.4–3.2)	.654	
 Lactate dehydrogenase (U/L)	309 (213–471)	396 (237–700)	.132	
 Glucose (mg/dL)	106 (93–121)	106 (88–121)	.911	
Corticosteroid treatment	
 Usage n (%)	9 (30)	8 (22.9)	.514	
 Duration (d) [median (IQR)]	1 (1–3)	1 (1–8)	.743	
Abbreviations: COPD = chronic obstructive pulmonary disease, CRP = C-reactive protein, IQR = interquartile range, pH = potential of hydrogen.

* Stands for normally distributed parameters and expressed as mean ± standard deviation.

The outcomes of the multivariate regression analysis revealed that an longer duration of symptoms (OR = 1.10, 95% CI: 1.01–1.21, P < .033) and the presence of dyspnea (OR = 5,44 95% CI: 1.26–23.50, P < .023) independently associated with an increased need for invasive procedures, while corticosteroid treatment (OR = 0.15, 95% CI: 0.02–0.81, P < .028) was observed to be associated with a reduced necessity for invasive procedures (Table 3).

Table 3 Multivariate logistic regression analysis demonstrating the independent predictors for the requirement to invasive procedure.

	Odds ratio	Confidence interval (95%)	P value	
Dyspnea	5.44	1.26 to 23.50	.023	
Symptom duration (d)	1.10	1.01 to 1.21	.033	
Steroid usage	0.15	0.02 to 0.81	.028	

After performing ROC analyses, an AUC of 0.617 was found for symptom duration to predict invasive procedures, and the cutoff value was determined as 13 days. Considering this cutoff value for symptom duration, the diagnostic test results were presented in Table 4.

Table 4 Diagnostic results of the symptom duration in predicting invasive procedure need.

Symptom duration	Value*	95% CI	
Sensitivity (%)	54.29	36.65 to 71.17	
Specificity (%)	76.67	57.72 to 90.07	
Positive likelihood ratio	2.33	1.14 to 4.77	
Negative likelihood ratio	0.6	0.4 to 0.91	
Positive predictive value (%)	73.08	57.01 to 84.75	
Negative predictive value (%)	58.97	48.79 to 68.45	
Accuracy (%)	64.62	51.77 to 76.08	
* Symptom duration ≥3 d vs <13 d.

4. Discussion

Our study showed that in adult patients diagnosed with PPE in the exudative phase where inflammation is prominent, the presence of dyspnea and a long duration of symptoms may increase the need for invasive procedure, whereas the use of corticosteroids was found to be associated with a lower need for invasive procedure. To the best of our knowledge, our study is the first to investigate the role of methylprednisolone in adult patients diagnosed with PPE in the exudative phase.

The potential effect of corticosteroid treatment in patients diagnosed with pneumonia have been frequently investigated. A meta-analysis conducted in patients with community-acquired pneumonia has shown that adding corticosteroids to the routine treatment reduced the length of hospital stay, increased recovery rates, and reduced mortality.[16] It has been reported that corticosteroids contribute to survival, especially in periods when high inflammation is observed in patients diagnosed with pneumonia.[17] The development of parapneumonic effusion in the course of pneumonia is not uncommon and morbidity and mortality seem to be higher.[18] In patients diagnosed with PPE, optimal medical treatment should be provided in the exudative period to avoid possible complications. However, there is scarce data on the potential efficacy of corticosteroid therapy to reduce the need for invasive procedures in this group of patients.

In a retrospective study conducted with 97 patients in the pediatric age group, it was shown that corticosteroid use in patients diagnosed with parapneumonic effusion could reduce the risk of interventional and surgical procedures as well as its effectiveness in reducing fever and hospital stay. No multivariate analysis was performed. So, any causal relationship and the independent effect of corticosteroid use could not be strongly reported. Additionally, patients diagnosed with PPE were evaluated independently of the stage.[11] However in our study, we have considered the parapneumonic effusion stage in the analyses. In a randomized controlled pilot study conducted in adults in 2022 (STOPPE study), the effectiveness of dexamethasone treatment in patients diagnosed with parapneumonic effusion was evaluated compared to placebo.[12] Further studies in disease subgroups were recommended in this study which included patients with parapneumonic pleural effusion at all stages although the need for invasive intervention was similar in the dexamethasone group and the placebo group. In a double-blind-randomized study conducted in the pediatric group of 60 patients, the effectiveness of adding i.v. dexamethasone (0.25 mg/kg every 6 hours over a period of 48 hours) to the routine antibiotic treatment was investigated.[10] In this study, 60 patients diagnosed with PPE were examined in subgroups as simple and complicated, 18 of the 36 patients found in the simple PPE group received dexamethasone treatment and the total treatment duration was found to be significantly lower compared to those who did not receive dexamethasone. No significant difference was observed in terms of complications and side effects related to dexamethasone in patients diagnosed with both simple and complicated effusion. The treatment duration was the primary endpoint of the study and did not provide any data on the need for invasive intervention. Although this study showed that the effectiveness of corticosteroid treatment in PPE subgroups, only 36 patients were diagnosed with simple PPE, and it was recommended to conduct studies with a larger number of patients in this patient group. In addition, these patients in the pediatric age group received dexamethasone treatment as a corticosteroid, and there is still uncertainty about the effectiveness of methylprednisolone.

Corticosteroids have been shown to reduce clinical recovery time, length of stay in hospital and intensive care unit, development of respiratory failure or shock not present at the onset of pneumonia, and pneumonia complication rates especially in patients with pneumonia who require hospitalization and are treated in intensive care units.[17,19,20] Although the anti-inflammatory effectiveness of dexamethasone has been well known,[21] there are also studies showing that the lung penetration of methylprednisolone is higher.[22] The effectiveness of methylprednisolone and dexamethasone has been compared in patients with COVID-19 pneumonia. According to the results of this study, high-dose methylprednisolone treatment statistically significantly reduced the recovery time and the need for transfer to intensive care compared to dexamethasone treatment.[23] Notably, in a randomized controlled study, it was shown that in patients with COVID-19 pneumonia who were treated as inpatients, methylprednisolone reduced the hospital stay and the need for noninvasive mechanical ventilation compared to dexamethasone treatment, and improved the “clinical status” on the 5th and 10th days of the treatment.[22] Along with these, since methylprednisolone is a corticosteroid that is more frequently used and monitored more conveniently in pulmonology practice, we believe that the results of our study, which includes only patients in the exudative phase and examines the effectiveness of methylprednisolone, might contribute to daily practice.

Our study had some limitations. First, this study was limited by its single center and retrospective nature. Since the retrospective design, time duration to invasive procedure was not clear and survival analysis could not be performed. Second, the indication of corticosteroid treatment was not clear. Third, the exclusion of the patients in whom thoracentesis was not performed may lead to selection bias. Fourth, the presence of dyspnea leads to an overestimation of the frequency of invasive procedures. Lastly, our study was limited by relatively small sample size.

5. Interpretation

As a conclusion; together with the absence of dyspnea and the shorter symptom duration, methylprednisolon treatment may independently decrease the need for invasive procedure in patients with parapneumonic pleural effusion in the exudative phase. Although methylprednisolon treatment has been shown to be beneficial in these patients, the optimal dosage and duration remains unclear. This study may shed light on further larger randomized controlled trials.

Author contributions

Data curation: Ali Kirac, Aysegul Erinc.

Formal analysis: Celal Satici.

Investigation: Ali Kirac, Aysegul Erinc, Filiz Kosar.

Methodology: Celal Satici.

Project administration: Filiz Kosar.

Resources: Aysegul Erinc.

Validation: Celal Satici, Aysegul Erinc.

Visualization: Celal Satici.

Abbreviations:

AUC area under the ROC curve

CI confidence interval

CRP C-reactive protein

Dl deciliter

INR international normalized ratio

IQR interquartile range

LDH lactate dehydrogenase

OR odds ratio

pH power of hydrogen

PPE parapneumonic effusion

ROC receiver operating characteristic

TT-UWSD tube thoracostomy with underwater seal drainage

VATS Video Assisted Thoracoscopic Surgery

All authors have no conflicts of interest to declare.

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

How to cite this article: Kirac A, Satici C, Erinc A, Kosar F. The role of corticosteroids in preventing invasive procedures in patients with parapneumonic effusion in the exudative phase: An observational study. Medicine 2024;103:37(e39693).
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References

[1] Light RW Girard WM Jenkinson SG George RB . Parapneumonic effusions. Am J Med. 1980;69 :507–12.7424940
[2] Koegelenberg CF Diacon AH Bolliger CT . Parapneumonic pleural effusion and empyema. Respiration. 2008;75 :241–50.18367849
[3] Singh S Singh SK Tentu AK . Management of parapneumonic effusion and empyema. J Assoc Chest Physicians. 2019;7 :51–8.
[4] Ferguson AD Prescott RJ Selkon JB Watson D Swinburn CR . The clinical course and management of thoracic empyema. QJM. 1996;89 :285–9.8733515
[5] Nasreen N Mohammed KA Hardwick J . Polar production of interleukin-8 by mesothelial cells promotes the transmesothelial migration of neutrophils: role of intercellular adhesion molecule-1. J Infect Dis. 2001;183 :1638–45.11343213
[6] Kroegel C Antony VB . Immunobiology of pleural inflammation: potential implications for pathogenesis, diagnosis and therapy. Eur Respir J. 1997;10 :2411–8.9387973
[7] Shen KR Bribriesco A Crabtree T . The American Association for Thoracic Surgery consensus guidelines for the management of empyema. J Thorac Cardiovasc Surg. 2017;153 :e129–46.28274565
[8] Yu L Krasna MJ . Parapneumonic empyema. In: Shields TW Locicero J Reed C Feins RH , editors. Thoacic surgery. Phildelphia: Lippincott Williams and Wilkins; 2009:775–9.
[9] Kesieme EB Dongo A Ezemba N Irekpita E Jebbin N Kesieme C . Tube thoracostomy: complications and its management. Pulm Med. 2012;2012 :256878.22028963
[10] Tagarro A Otheo E Baquero-Artigao F .; CORTEEC Study Group. Dexamethasone for parapneumonic pleural effusion: a randomized, double-blind, clinical trial. J Pediatr. 2017;185 :117–23.e6.28363363
[11] Thimmesch M Mulder A Lebrun F . Management of parapneumonic pleural effusion in children: is there a role for corticosteroids when conventional nonsurgical management fails? A single-center 15-year experience. Pediatr Pulmonol. 2022;57 :245–52.34559458
[12] Fitzgerald DB Waterer GW Budgeon C . Steroid therapy and outcome of parapneumonic pleural effusions (STOPPE): a pilot randomized clinical trial. Am J Respir Crit Care Med. 2022;205 :1093–101.35081010
[13] Çayakar A . Steroid usage in clinical practice. J Turk Soc Rheumatol. 2021;13 :73–84. doi:10.4274/raed.galenos.2020.91885.
[14] Davies HE Davies RJ Davies CW ; BTS Pleural Disease Guideline Group. Management of pleural infection in adults: British thoracic society pleural disease guideline 2010. Thorax. 2010;65 (Suppl 2 ):ii41–53.20696693
[15] Birkenkamp K O’Horo JC Kashyap R . Empyema management: a cohort study evaluating antimicrobial therapy. J Infect. 2016;72 :537–43.26987740
[16] Huang J Guo J Li H Huang W Zhang T . Efficacy and safety of adjunctive corticosteroids therapy for patients with severe community-acquired pneumonia: a systematic review and meta-analysis. Medicine (Baltimore). 2019;98 :e14636.30921179
[17] Ceccato A Russo A Barbeta E . Real-world corticosteroid use in severe pneumonia: a propensity-score-matched study. Crit Care. 2021;25 :432.34915895
[18] Bedawi EO Hassan M Rahman NM . Recent developments in the management of pleural infection: a comprehensive review. Clin Respir J. 2018;12 :2309–20.30005142
[19] Siemieniuk RA Meade MO Alonso-Coello P . Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med. 2015;163 :519–28.26258555
[20] Stern A Skalsky K Avni T Carrara E Leibovici L Paul M . Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017;12 :CD007720.29236286
[21] Schimmer BP Funder JW . ACTH, Adrenal Steroids, and Pharmacology of the Adrenal Cortex. In: Brunton LL Chabner BA Knollmann BC (Eds). Goodman & Gilman’s: the pharmacological basis of therapeutics. 12th ed. USA: McGraw-Hill Education; 2011.
[22] Ranjbar K Moghadami M Mirahmadizadeh A . Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial. BMC Infect Dis. 2021;21 :337. Erratum in: BMC Infect Dis. 2021 May 11;21(1):436.33838657
[23] Pinzón MA Ortiz S Holguín H . Dexamethasone vs methylprednisolone high dose for Covid-19 pneumonia. PLoS One. 2021;16 :e0252057.34033648
