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Effect of perioperative methylprednisolone administration on postoperative pleural effusion in older patients with non-small cell lung cancer

BMC Anesthesiology volume 25, Article number: 20 (2025) Cite this article

Abstract

Background

It remains uncertain whether the utilization of methylprednisolone during surgery effectively mitigates the occurrence of adverse outcomes. To examine the association between perioperative methylprednisolone administration and postoperative pleural effusion and pneumonia in older patients with non-small cell lung cancer.

Methods

A retrospective cohort study included non-small cell lung cancer patients aged 65 years or older undergoing thoracic surgery between January 2012 and December 2019 in China. Primary outcome was pleural effusion. Secondary outcome was postoperative pneumonia. Multivariate logistic regression models assessed the independent effects of various factors on pleural effusion and pneumonia. Propensity score matching (PSM) method reduced selection bias enhancing causal inference validity. Subgroup analyses identified potential effect heterogeneity in specific sub-populations.

Results

A total of 1951 older patients with non-small cell lung cancer were included. The incidence of postoperative pleural effusion in the methylprednisolone group before and after PSM matching was significantly lower than that in the control group (before PSM: 9.4% vs. 19.2, P < 0.001; after PSM: 9.8% vs. 18.2%, P < 0.001). There was no statistically significant difference in the incidence of postoperative pneumonia between the two groups before and after matching. After adjusting all the variables and PSM, we found that intraoperative methylprednisolone was associated with a reduction in postoperative pleural effusion in older patients with non-small cell lung cancer [odds ratio (OR) = 0.48, P < 0.001; OR = 0.47, P < 0.001]. Perioperative methylprednisolone showed consistent protective effects in all sub-populations of gender, age, surgery duration, and smoking (P all < 0.05). Logistic regression models and PSM found that methylprednisolone was not associated with postoperative pneumonia and long-term survival in older patients with non-small cell lung cancer.

Conclusion

Perioperative methylprednisolone was associated with reducing the occurrence of postoperative pleural effusions in older patients with non-small volume lung cancer, but it was not associated with pneumonia or long-term survival outcomes.

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Background

Lung cancer, a significant global health concern, remains a leading cause of disease-related mortality among patients [1]. Specifically, non-small cell lung cancer (NSCLC), a malignant neoplasm arising from non-small cell types of lung tissue, constitutes approximately 85–90% of all lung cancer cases [2]. In contrast to small cell lung cancer, NSCLC exhibits a slower growth rate, less frequent metastasis, and distinct therapeutic approaches [3, 4]. Surgery is a cornerstone of treatment for thoracic cancer patients, particularly those with early-stage lung cancer. Postoperative surgical trauma triggers a series of stress responses in the body, which may result in tissue damage, ischemia, hypoxia, and inflammation. This high incidence of complications following lung cancer surgery remains a critical challenge that clinical practitioners must address with sufficient attention.

Hormonal drugs used during surgery typically include methylprednisolone, which is used to regulate the immune system, reduce inflammatory and allergic reactions, and promote the recovery of adrenal function [5, 6]. Bressan et al. revealed that the use of a single dose of methylprednisolone can significantly shorten the hospital stay, postoperative infectivity, and overall complications of liver resection patients [7]. But turan et al. confirmed that methylprednisolone did not alleviate postoperative pain in patients undergoing cardiac surgery [8]. A prospective meta-analysis of clinical trials in patients with COVID-19 found that administration of systemic corticosteroids was associated with lower 28-day all-cause mortality compared with placebo [9]. The use of hormones in the perioperative period is a complex and controversial topic. Research should continue to explore its impact on postoperative complications and provide clearer clinical guidance to improve postoperative outcomes for patients.

The purpose of this study is to investigate the association of methylprednisolone with postoperative pleural effusion and pneumonia in older patients with NSCLC through retrospective analysis of structured big data. This study provides clinicians with an evidence base for the use of methylprednisolone, and helps formulate treatment strategies that are more in line with the characteristics of older patients with NSCLC.

Methods

Study design

This study was a retrospective cohort study. The Ethics Committee Board of the First Medical Centre of Chinese PLA General Hospital waived the need for informed consent (S2019-311-03). All enrolled patients were divided into two groups according to the presence of the perioperative administration of methylprednisolone before and after the propensity score matching (PSM). The main surgical indications included (1) patients had a clinical diagnosis of lung cancer (stage I, II, and III), (2) patient’s chest wall and mediastinum were not involved by cancer cells, (3) patients did not have myocardia infraction or the tendency to severe bleeding recently, and (4) patients were tolerable to single lung ventilation. This study complied with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines and adhered to the Declaration of Helsinki [10].

Establishment of database

The study extracted 1951 NSCLC patients for analysis between January 2012 and December 2019 from the Geriatric Thoracic Perioperative Database (GTPD) in the First Medical Centre of Chinese PLA General Hospital (Beijing). The database was established by collecting 3009 order patients treated with thoracic surgery, and it was developed using the Web-Service interface that could automatically extract clinical characteristics from the electronic medical record system, clinical laboratory examination system, medical imaging system, blood transfusion system, doctor’s prescription system, and nurse workstation. The database contained patient’s diagnoses, comorbidity, prescriptions, laboratory tests, medical expenses, and perioperative medications.

Data standardization was in line with the Clinical Data Interchange Standards Consortium (CDISC). In addition, adopt the method of independent data entry by two people and cross-check to reduce input errors. Regularly cleans the entered data to check for missing values, outliers, and logical errors. Data recovery processes and tests have been established to ensure that data can be recovered quickly and accurately when needed.

Inclusion and exclusion criteria

We included patients with an age of 65 or above years who treated with thoracic surgery and had a histologic diagnosis of NSCLC. The exclusive criteria were as follows: (1) if the patient had two or more hospital admissions, only the first one was included for analysis; (2) patients treated with chest surgery due to oesophageal cancer, gastric antral cancer, thymic carcinoma, bullae of lung, and other thoracic cancers rather than lung cancer; (3) patients had a diagnosis of small cell lung cancer. Figure 1 presents the flow chart of patients and the study design.

Fig. 1
figure 1

Flow chart of patients and study design

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Clinical characteristics

Patient’s basic characteristics were divided into seven classifications and there were (1) basic demographics, including gender, age, smoking status, body mass index (BMI), (2) surgery-related information, including surgical site, type of surgery, lymphadenectomy, open surgery, and American Society of Anaesthesiologists (ASA), (3) comorbidities, including diabetes, hypertension, coronary heart disease, and chronic obstructive pulmonary disease (COPD), (4) laboratory examinations, including serum albumin, leukocyte count, and haemoglobin (Hb), (5) perioperative administration of drugs, including blood loss, colloid, crystalloid, and perioperative blood transfusion, and tumour size. Comorbidities were collected based on the medical records. Tumour size was evaluated by postoperative pathological specimen. The above-mentioned characteristics were compared between the two groups according to the presence of the perioperative administration of methylprednisolone before and after the PSM. Postoperative survival prognosis was defined as the time interval between surgery date and the death date. We checked patient’s death date in the Chinese Center for Disease Control and Prevention and the last follow-up date of the study was September 1, 2021. The median follow-up time was 4.6 years.

Definition of the outcomes

Postoperative pleural effusion or pneumonia is diagnosed by referring to the European perioperative clinical outcome (EPCO) criteria, such as clinical symptoms, physical examination, imaging monitoring (CT/X-ray), laboratory tests, oxygen and status assessment, and microbiological testing techniques. If a patient previously suffered from pleural effusion before surgery and the effusion was enlarged after surgery, the patient was regarded as having positive postoperative pleural effusion. Furthermore, patients might also had symptoms, such as dyspnoea and chest wall pain, and physical examinations, including asymmetric expansion of thoracic cage with declined expansion on the affected side, diminished or inaudible breath sounds, dullness or decreased resonance to percussion, and decreased tactile fremitus [11]. The primary outcome was compared between the two groups according to the presence of the perioperative administration of methylprednisolone before and after the PSM.

Postoperative pneumonia should also be supported by the one or more following clinical manifestations after surgery during hospitalization [12], including (1) patients suffered from newly or progressively respiratory presentations, such as coughing and expectoration; (2) patients had a temperature of more than 38℃ or hypothermia; (3) patients had a physical examination of lung consolidation signs or moist rale; (4) the white cell count of patient’s blood was more than 10 × 109/L or less than 4 × 109/L; (5) patients had a new rise in the C-reactive; (6) blood culture or sputum culture showed pathogen isolation.

Statistical analysis

Statistical descriptions of all patients were performed according to the presence of the perioperative administration of methylprednisolone before and after the PSM. A median supplied with interquartile range (IQR) was used to describe quantitative variables which were not normally distributed, and qualitative variables were presented in ratio. The Wilcoxon test was used to compare the difference of quantitative variables between patients with and without perioperative administration of methylprednisolone; the Chi-square test and continuity adjusted Chi-square test were used to make a comparison for quantitative variables. Survival analysis was performed to analyse postoperative survival outcome and Kaplan-Meier method and the log-rank test was used to plot survival curves and compare differences between the two groups before and after the PSM. PSM was conducted to adjust for confounding variables and reduce potential baseline inequalities between the two groups [5]. Propensity scores were estimated by a PSM model including all significant different variables between the two groups before PSM. A “match method = nearest” with a ratio of 1 to 1 algorithm and “caliper width = 0.02” was performed to create two new cohorts which had the same number of patients and similar baseline characteristics according to the propensity scores. Standardized mean differences were calculated in the study. Furthermore, the forward stepwise logistic regression analysis was performed to evaluate the ability of methylprednisolone to predict postoperative pneumonia and pleural effusion. All statistical analyses were conducted using R statistical software (R Project for Statistical Computing, version 4.1.2). Hypothesis tests were 2-sided with significance set at P < 0.05.

Results

Baseline demographics

1951 patients met inclusive criteria and were enrolled for analysis in this study. In the series of cohorts, 14.0% (274/1951) had postoperative pleural effusion and 9.6% (188/1951) suffered from postoperative pneumonia. Table 1 showed the patient’s baseline characteristics according to the presence of methylprednisolone before propensity matching. It demonstrated that, before PSM, patients with perioperative methylprednisolone had a higher BMI (P = 0.008), less open surgery (P < 0.001), less blood loss (P < 0.001), and a smaller tumour size (P = 0.008), as compared to patients without perioperative administration of methylprednisolone.

Table 1 Patient’s baseline characteristics according to the presence of the perioperative administration of methylprednisolone before propensity score matching analysis
Full size table

After PSM, 1476 patients were successfully matched based on a 1 to 1 ratio, and thus there were 738 patients with perioperative methylprednisolone and the same number of patients without it. Table 2 showed the matched two cohorts had very similarly distributed baseline characteristics, and all the standardized mean differences were all decreased, indicating that the confounding factors were considerably controlled. Figure 2 showed that the matched treated and control cohorts both had the same proportion in different propensity scores after propensity matching. Supplement Fig. 1 showed the distribution of propensity scores for the matched and unmatched cohorts among treated and control units.

Table 2 Patient’s baseline characteristics according to the presence of the perioperative administration of methylprednisolone after propensity score matching analysis
Full size table
Fig. 2
figure 2

The matched treated and control cohorts before and after propensity matching analysis. A. Raw treated cohort; B. Matched treated cohort; C. Raw control cohort; D. Matched treated cohort

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PSM of pleural effusion and pneumonia

The methylprednisolone was an independent predictor of pleural effusion. To investigate the correlation between methylprednisolone and outcomes, we used 4 logistic regression models. In the result of model 4 (adjusted all the variables), the methylprednisolone was a protection factor of postoperative pleural effusion (OR: 0.48, 95% CI: 0.36–0.64, P < 0.001). In the logistic regression performed after PSM, the methylprednisolone was still an protection predictor of pleural effusion (OR: 0.47, 95% CI: 0.35–0.68, P < 0.001; Table 3). However, we found that in model 4 the methylprednisolone was not an independent predictor of postoperative pneumonia (OR: 1.36, P = 0.063). After PSM, the methylprednisolone also was not still an independent predictor of pneumonia (P = 0.742; Table 3). We found that the intraoperative dose of methylprednisolone in older patients with postoperative pleural effusion was significantly lower than that without pleural effusion (before PSM: median (IQR) 22.89 (21.36) vs. 15.62 (22.87), P < 0.001; after PSM: 21.57 (22.32) vs. 14.42 (23.40), P < 0.001, Supplement Table 1). We did not find an association between methylprednisolone doses and postoperative pneumonia in older patients with NSCLC.

Table 3 Association between methylprednisolone and postoperative pneumonia and pleural effusion with logistic regression models and propensity score analysis
Full size table

Survival and subgroup analyses

There were no significant differences between the two groups in terms of postoperative survival outcome (Fig. 3A and B) before (P = 0.52) and after PSM (P = 0.48). Subgroup analyses showed that perioperative methylprednisolone had a consistently significant protective effect on postoperative pleural effusions in all subgroup populations of gender, age, duration of surgery, and smoking (all P < 0.05, Fig. 4). Perioperative methylprednisolone was found to be associated with a reduction in pleural effusion in both male and female subgroups (Female: OR = 0.335, 95% CI: 0.207–0.531, P < 0.001; male: OR = 0.507, 95%CI: 0.365–0.699, P < 0.001). The ORs of the methylprednisolone were significant for age subgroups in postoperative pleural effusion (65 ~ 70 years: OR = 0.424, 95% CI: 0.298–0.598, P < 0.001; ≥70 years: OR = 0.457, 95%CI: 0.301–0.685, P < 0.001). In the subgroup of duration of surgery, we found a more pronounced trend towards a more significant reduction of postoperative pleural effusion in the subgroup of < 180 min (< 180 min: OR = 0.291, 95% CI: 0.195–0.427, P < 0.001; ≥180 min: OR = 0.667, 95% CI: 0.454–0.977, P < 0.001). It was important to note that perioperative methylprednisolone only produced a significant protective effect in postoperative pleural effusions in older patients with < 2 cumulative comorbidities, but not in older patients with ≥ 2.

Fig. 3
figure 3

Kaplan‒Meier survival curves for overall survival of order NSCLS patients with or without methylprednisolone. Red line indicates that methylprednisolone was not used perioperatively. Blue line represents the perioperative use of methylprednisolone

Full size image
Fig. 4
figure 4

Subgroup analyses of the association between methylprednisolone and postoperative pleural effusion. OR, odds ratio. CI, confidence interval

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Discussion

We retrospectively analyzed structured data from 1952 older surgical patients over 65 years of age who underwent non-small cell lung cancer (NSCLC). In this study, we found that perioperative methylprednisolone appeared to be associated with a reduction in postoperative pleural effusion in older patients with NSCLC. It is important to note that our results did not find a significant positive effect of perioperative methylprednisolone on postoperative pneumonia and long-term survival in older patients with NSCLC.

This study suggested that perioperative methylprednisolone was associated with a reduction of postoperative pleural effusion in patients with NSCLC, consistent with the existing literature on the benefits of steroids in the treatment of postoperative complications [13,14,15]. Pleural effusion formation is complex and influenced by various factors, including postoperative inflammatory status, fluid management, and activity levels. While methylprednisolone improves local inflammation, its broader efficacy in managing postoperative complications requires further investigation. Methylprednisolone could prevent fluid buildup in the pleural cavity by reducing the permeability of blood vessels, reducing fluid and protein leakage. This effect helps to reduce the accumulation of fluid after surgery [16, 17]. Strategies like fluid management, early mobilization, and respiratory function optimization are also crucial in preventing pleural effusion. Methylprednisolone could effectively reduce the occurrence of postoperative pleural effusion through multiple mechanisms such as anti-inflammatory effects, reduced vascular permeability, improved fluid metabolism, and reduced postoperative pain [18, 19]. This finding provides a new perspective on perioperative management and highlights the potential benefits of rational use of methylprednisolone in clinical practice.

The impact of perioperative hormone use on postoperative pneumonia remains contentious, requiring further research to establish its efficacy and safety. Ito et al. found that perioperative use of methylprednisolone did not have any protective effects for acute exacerbation of interstitial pneumonia after lung cancer surgery in a phase II clinical trial after enrolling a series of 69 patients [20]. A 2022 study by Meduri et al. showed that low-dose methylprednisolone had no significant effect on morbidity and survival in patients with severe pneumonia [21]. A multicentre clinical trial indicated that a continuous intravenous infusion of hydrocortisone could decrease the risk of hospital-acquired pneumonia after analysing 150 patients with severe trauma who admitted to ICU in France [22]. Another clinical trial showed the similar effect among patients with severe traumatic brain injury [23]. However, the results of a 2020 single-blind, randomized controlled trial showed that methylprednisolone is an effective treatment for hospitalized patients with severe pneumonia [24]. Tabatabai et al. found that methylprednisolone use was associated with a high rate of infection, but the sample in this retrospective study was very limited (82 cases) and this study included patients with veno-venous extracorporeal membrane oxygenation [25]. The above-mentioned conclusions were controversial and might possibly be expounded by the heterogeneities of population, differences in pharmacological actions of drugs, and patterns of drug administration. Unlike hydrocortisone, methylprednisolone had longer and stronger pharmacological effects, and the present study included lung cancer patients undergoing thoracic surgery and methylprednisolone was perioperatively given for one time.

When exploring the reasons why methylprednisolone fails to effectively reduce the occurrence of pneumonia in patients with NSCLC after surgery, it is necessary to recognize its complex immunomodulatory effects. Pneumonia is a multi-factorial issue influenced by the patient’s immune status, respiratory function, and pathogen exposure [26]. The immunosuppressive properties of methylprednisolone may increase infection risk, especially amid surgical stress and mobility restrictions. Additionally, it has limited efficacy against various pneumonia pathogens, including bacteria, viruses, and fungi, and may not effectively prevent pneumonia from inhalation injuries. Individual patient differences, such as underlying conditions and age, also play a crucial role in pneumonia risk. Future research should explore how methylprednisolone can be combined with other interventions to improve postoperative outcomes.

Clemmesen et al. demonstrated that methylprednisolone is not capable of preventing postoperative delirium among hip fracture patients [19]. Kerret al. found that perioperative administration of methylprednisolone was unable to reduce the incidence of lung injury among pulmonary thromboendarterectomy surgery after enrolling 98 adult patients [27], despite the fact that methylprednisolone might have a role in regulating anti-inflammatory cytokine levels, such as a reduction in plasma IL-6 and IL-8. The above findings indicated that perioperative methylprednisolone might have limited effects on preventing postoperative complications.

In this study, we did not find an association between perioperative methylprednisolone and long-term survival after surgery. The main effect of methylprednisolone is to reduce inflammation and complications (e.g., pleural effusion) in the perioperative period, but its effect on tumor biology and behavior may be small and it is not effective in changing the long-term behavior pattern of tumors. Methylprednisolone as a monotherapy may not be effective in improving long-term outcomes. Cancer treatment often requires a comprehensive approach, including surgery, radiotherapy, chemotherapy, and targeted therapy, and a single drug intervention may not be sufficient to change disease progression.

This study had several limitations. Firstly, this was a retrospective observational study, so selection bias still existed. But this study conducted propensity score matching to adjust for confounding variables and reduce potential baseline inequalities. Thus, selection bias could be largely avoided. Secondly, retrospective studies can only find associations, not prove causation. Although methylprednisolone may be found to be associated with reduced pleural effusion, there is no definitive evidence that this drug directly causes this effect. Similarly, the relationship between methylprednisolone and postoperative pneumonia cannot be determined by this design. Thirdly, other variables, such as the forced expiratory volume in one second/forced vital capacity ratio, which has been associated with postoperative pneumonia in lung cancer patients in other studies [28], were not collected in this study due to data unavailability. Fourthly, the dose and duration of methylprednisolone received by different patients may vary, which can affect the results of the study. The lack of standardized treatment regimens increases the heterogeneity of outcomes and limits their broad applicability.

Conclusions

Perioperative methylprednisolone was associated with a reduction in postoperative pleural effusion in patients with non-small cell lung cancer over 65 years of age, but not with postoperative pneumonia and long-term survival. This study provides research evidence and direction for the intervention and treatment strategies of postoperative pleural effusion in older patients over 65 years of age with non-small cell lung cancer.

Data availability

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

Abbreviations

ASA:

American society of anaesthesiologists

BMI:

Body mass index

COPD:

Chronic obstructive pulmonary disease

ICU:

Intensive care units

IQR:

Interquartile range

SMD:

Standard mean difference

RDW:

Red blood cell volume distribution width

OR:

Odd ratio

CI:

Confidence Interval

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Acknowledgements

The authors thank of Shanghai Lejiu Healthcare Technology for their technical assistance in data extraction and statistical analyses.

Funding

This research was supported by the National Key Research and Development Program of China to Weidong Mi [grant number: 2018YFC2001900] and did not receive any grant from funding agencies in the public or commercial sectors.

Author information

Author notes

  1. Xinyu Hao, Yongxin Guo and Ziyao Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, The First Medical Centre of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China

    Xinyu Hao, Yongxin Guo, Likai Shi, Qiang Fu, Wenzhu Shi, Jiangbei Cao, Yanhong Liu, Li Tong & Weidong Mi

  2. Department of General surgery, The First Medical Centre of Chinese PLA General Hospital, Beijing, 100853, China

    Ziyao Xu

  3. Department of Anesthesiology, 922 Hospital of PLA, Hengyang, 421002, China

    Yanping Song

  4. Department of Anesthesiology, Beijing Corps Hospital of Chinese People’s Armed Police Force, Beijing, 100027, China

    Jingjing Liu

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  8. Wenzhu Shi
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  11. Li Tong
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Contributions

Xinyu Hao, Yongxin Guo and Ziyao Xu: Conceptualization, Methodology, Software. Ziyao Xu, Jingjing Liu and Yongxin Guo: Data curation, Writing Original draft preparation. Yanping Song and Jingjing Liu: Visualization, Investigation. Weidong Mi: Supervision.Li Tong: Software, Validation. Other authors: Writing- Reviewing and Editing.

Corresponding authors

Correspondence to Li Tong or Weidong Mi.

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Ethics approval and consent to participate

Ethical approval for this study (No. S2019-311-03) was approved by the Ethics Committee Board of the First Medical Centre of Chinese PLA General Hospital, Beijing, China on 11 March 2019 and the committee waived patient’s written consents due to anonymous data and retrospective study in nature.

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Not applicable.

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The authors declare no competing interests.

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Hao, X., Guo, Y., Xu, Z. et al. Effect of perioperative methylprednisolone administration on postoperative pleural effusion in older patients with non-small cell lung cancer. BMC Anesthesiol 25, 20 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12871-025-02891-9

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Keywords

BMC Anesthesiology

ISSN: 1471-2253

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