Application of methylene blue injection staining in the diagnosis of hepatic pleural effusion in patients with cirrhosis—a case report and literature review
Case Report

Application of methylene blue injection staining in the diagnosis of hepatic pleural effusion in patients with cirrhosis—a case report and literature review

Zhaoyang Xing1 ORCID logo, Hui Wang2

1Department of Critical Medicine, the First People’s Hospital of Guangyuan, Guangyuan, China; 2Clinical Medical Department, the Third People’s Hospital of Guangyuan, Guangyuan, China

Contributions: (I) Conception and design: Z Xing; (II) Administrative support: Z Xing; (III) Provision of study materials or patients: Z Xing; (IV) Collection and assembly of data: Both authors; (V) Data analysis and interpretation: Z Xing; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors.

Correspondence to: Zhaoyang Xing, BMed. Department of Critical Medicine, the First People’s Hospital of Guangyuan, No. 490 Juguo Road, Lizhou District, Guangyuan 628000, China. Email: 2253140533@qq.com.

Background: Hepatic pleural effusion is a common complication in patients with cirrhosis. The diagnosis of hepatic pleural effusion is limited by many factors. There are advantages and disadvantages to using radioisotope examination, contrast-enhanced ultrasound and video-assisted thoracoscopy surgery in detecting diaphragmatic defects. We reported that methylene blue injection was injected into the peritoneal cavity, and pleural effusion was turned pale blue with methylene blue. We inferred diaphragmatic rupture in patients with hepatic pleural effusion. Methylene blue injection staining is a supplementary method for the diagnosis of diaphragmatic rupture in patients with hepatic pleural effusion.

Case Description: The patient is an 83-year-old patient who was admitted to hospital with respiratory failure. The ultrasound showed a large right pleural effusion and ascites. A computed tomography scan showed no lung infection. The patient has cirrhosis for 20 years. We performed endotracheal intubation and mechanical ventilation. A drainage tube was placed in the patient’s right pleural cavity. We injected 2 mL of methylene blue into the patient’s peritoneal cavity. After 2 hours, the right pleural cavity drainage appears light blue. Based on this, we assume the patient’s diaphragm ruptured. The patient was diagnosed with hepatic pleural effusion. We did a comprehensive treatment for the pleural effusion. Repeated increase of pleural effusion. The patient died 62 days after admission.

Conclusions: Methylene blue injection staining is a supplementary method for the diagnosis of diaphragmatic rupture in patients with hepatic pleural effusion. It is suitable for areas lacking detection methods.

Keywords: Pleural effusion; methylene blue; hydrothorax; cirrhosis; case report

Received: 08 February 2025; Accepted: 09 May 2025; Published online: 10 September 2025.

doi: 10.21037/acr-25-41

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Key findings

• To determine whether the patient with liver cirrhosis combined with pleural and peritoneal effusion had a diaphragm rupture, we injected methylene blue injection into the peritoneal cavity and observed that the pleural effusion was stained blue by methylene blue after 2 hours.

What is known and what is new?

• Currently the radioisotope diagnostic techniques, color Doppler imaging, magnetic resonance imaging and video-assisted thoracoscopy are used for diagnosing diaphragmatic rupture. However, these methods have drawbacks. such as difficulty in obtaining, high cost, and inability to detect minor cracks.

• Methylene blue injection staining is a supplementary method for the diagnosis of diaphragmatic rupture in patients with hepatic pleural effusion.

What is the implication, and what should change now?

• Methylene blue staining is easy to implement, inexpensive, radiation free and minimally invasive. It is suitable for areas lacking testing methods.

Introduction

Hepatic pleural effusion refers to pleural effusion in patients with cirrhosis, but the pleural effusion is not caused by heart disease or lung disease (1-3). Usually, the volume of pleural effusion is greater than 500 mL. Pleural effusion usually occurs in the right thoracic cavity (85%) (4). The incidence rate of hepatic pleural effusion in patients with liver cirrhosis ranges from 2.1% to 30.3% in China (5). The median survival of patients with hepatic pleural effusion is 8–12 months (6,7). One of the pathogeneses of hepatic pleural effusion is the displacement of peritoneal effusion into the pleural cavity through the rupture of the diaphragm tendon (5). Diaphragmatic rupture usually occurs in the right diaphragmatic muscle (6). There are four types of diaphragmatic rupture: (I) no obvious defects; (II) blebs lying on the diaphragm; (III) broken defects in the diaphragm; and (IV) multiple gaps in the diaphragm (8).

One diagnostic technique for detecting hepatic pleural effusion is to inject 99mTc-labelled human albumin into the peritoneal cavity and detect 99mTc in the pleural effusion (9). However, this technique requires radiation exposure and multiple film scanning procedures. In addition, case reports describe the use of color Doppler and magnetic resonance tomography to diagnose diaphragmatic rupture (10). Video-assisted thoracoscopy can be used to examine diaphragmatic rupture and perform necessary repairs (11). Each technique for detecting diaphragmatic rupture has some advantages and disadvantages. In this study, the purpose of reporting this case is to introduce methylene blue staining of pleural effusion as a supplementary method for diagnosing diaphragmatic rupture. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-25-41/rc).

Case presentation

The patient is 83 years old and he is male. His chief complaint was that he had trouble breathing for 2 days. He had cirrhosis of the liver for 20 years. He was hospitalized for treatment due to liver cirrhosis. He was not infected with the virus that caused liver damage. The cause of liver cirrhosis in this patient was unclear. He received medication to promote liver cell production. His liver function has been deteriorating year by year. His temperature was 36 ℃. His heart rate was 189 beats per minute and his breathing rate was 30 beats per minute. His blood pressure was 121/77 mmHg. His saturation pulse oxygen was 89%. The sound of his breathing in his right lung was gone. The computed tomography scan showed no bilateral lung infection. The computed tomography scan of the patient showed massive right pleural effusion, cirrhosis, and peritoneal effusion. The blood test results of patient showed decreased serum albumin and thrombocytopenia (Table 1). A drainage tube was inserted into the patient’s right pleural cavity. The pleural effusion was pale yellow (Figure 1). The pleural effusion was not infectious (Table 2). The volume of pleural effusion was about 1,000 mL per day. We suspected that the patient had developed hepatic pleural effusion. The daughter of the patient refused thoracoscopy examination. We stained the peritoneal fluid with methylene blue injection. The ultrasound was used to measure the ascites volume and select the puncture site. We injected 20 mg methylene blue injection (H32024827, Qihua Pharmaceutical Group Co., Ltd., Jinan, China) into abdominal cavity of the patient (Figure 2). Two hours later, the pleural effusion was stained light blue (Figure 3). It indicated that peritoneal fluid has entered the chest cavity. Based on this, we speculated that the patient had a diaphragm rupture. The patient was diagnosed with hepatic pleural effusion, respiratory failure, cirrhosis, and ascites. The patient had a large amount of pleural effusion and decreased blood volume. We injected fresh frozen plasma and human serum albumin to the patient. We used antibiotics to prevent infections of the patient. We provided nutritional treatment to the patient. Although various methods were used to reduce the pleural effusion, the patient died of liver failure after 62 days of hospitalization. The patient did not experience any adverse or unexpected events due to the injection of methylene blue.

Table 1

Blood test results

Parameter On admission Normal range
Hemoglobin (g/L) 9.1 11.5–17.5
Total leukocyte count (cells per mm3) 8,750 3,500–9,500
Platelet count (cells per mm3) 7,000 125,000–350,000
Serum lactate dehydrogenase (U/L) 462 100–248
Total serum protein (g/L) 6.39 6.5–8.5
Serum albumin (g/L) 2.35 4.0–5.5
Serum globulin (g/L) 3.63 2.5–3.5
Total bilirubin (μmol/L) 18.2 1.7–28
Direct bilirubin (μmol/L) 7.9 0–6.8
Alanine aminotransferase (U/L) 88 9–50
Aspartate aminotransferase (U/L) 107 8–40
Alkaline phosphatase (U/L) 397 45–125
Prothrombin time (seconds) 14.3 9–14
Blood ammonia (μmol/L) 79.8 18–72
Amino-terminal pro-brain natriuretic peptide (pg/mL) 4,704 0–521

The blood test results of patient showed decreased serum albumin and thrombocytopenia.

Figure 1 Unstained pleural effusion. The pleural effusion was pale yellow.

Table 2

Pleural effusion test results

Parameter On admission Normal range
Color Canary yellow –
Freezing Yes –
Qualitative characterization of protein Negative –
Eukaryote count in pleura effusion (cells per mm3) 78 0–600
Leukocyte count in pleura effusion (cells per mm3) 76 –
Erythrocyte count in pleura effusion (cells per mm3) 1,000 –
Percentage of mononuclear (%) 76.40 –
Mono nuclear count (cells per mm3) 58 –
Percentage of multiple nuclear (%) 23.60 –
Multiple nuclear count (cells per mm3) 18 –
Total protein (g/L) 7.3 0–30.0
Adenine dreaminess (U/L) 3 0–15
Lactate dehydrogenase (U/L) 76 100–248
Glucose (mmol/L) 19.03 3.6–5.5

The pleural effusion was not infectious.

Figure 2 The color of the methylene blue injection. Methylene blue injection (H32024827, Qihua Pharmaceutical Group Co., Ltd.).
Figure 3 Pleural effusion stained with methylene blue injection. Two hours later, the pleural effusion was stained light blue.

Timeline

We installed a drainage tube into right pleural cavity of the patient on the 1st day after hospitalization. The volume of pleural effusion was about 1,000 mL per day. We stained the peritoneal fluid with methylene blue injection on the 5th day after hospitalization (Figure 4).

Figure 4 Timeline. We stained the peritoneal fluid with methylene blue injection on the 5th day after hospitalization. CT, computed tomography.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Because the patient had passed away, written informed consent was obtained from the patients’ daughter for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Hepatitis B is currently the leading cause of cirrhosis in China. Hepatic pleural effusion leads to increased mortality of cirrhosis (12). The mechanism of hepatic pleural effusion is unclear (6,13). Several mechanisms have been proposed to explain the occurrence of hepatic pleural effusion (14,15). The most widely accepted explanation is that fluid from the abdominal cavity enters the pleural cavity through the rupture of the diaphragm (16-18). Several studies based on radiometric imaging have confirmed diaphragmatic rupture in patients with cirrhosis (19,20). In a previous study utilizing video thoracoscopy examination, Huang et al. (21) proposed four different types of diaphragmatic rupture related to hepatic pleural effusion. The muscle composition of the right diaphragm is less than that of the left diaphragm (18). Therefore, the incidence of rupture of the right diaphragm is higher (22).

We first rule out pleural effusion due to infection or tumor. Then we diagnosed hepatic pleural effusion according to the patient’s clinical manifestations, the results of pleural effusion detection and pleural puncture and drainage. The dosage of methylene blue injection is 20 mg, 10 mg or less, as long as it can fully stain the pleural fluid. We conducted an experiment before injecting methylene blue into this patient. We injected 20 mg methylene blue injection into 3,000 mL of 0.9% saline solution and observed that the saline solution was fully stained. The dosage of methylene blue may affect sensitivity. For example, nuclear scan and enhanced ultrasound are both dose dependent. At present, there is a lack of reference literature on the appropriate dosage of methylene blue injection for staining pleural effusion. A single intravenous injection of methylene blue injection can reach 20 mg per kilogram of body weight. So, the dosage of methylene blue used for staining is sufficiently safe. If a patient has a unilateral (especially right-sided) effusion without underlying heart, lung, or kidney pathology, the patient may have developed a hepatic pleural effusion. Pleural puncture fluid extraction is very important for diagnosing hepatic pleural effusion. In cases of diagnostic uncertainty (e.g., in the absence of known liver disease or as cites) imaging techniques such as cinematography, color Doppler, and magnetic resonance imaging may be used to confirm the migration of fluid through the diaphragm (19,20,23-26). Each technique for detecting diaphragmatic rupture has some advantages and disadvantages (Table 3).

Table 3

Methods for examination of diaphragmatic rupture

Method Advantage Disadvantage Reference
VATS Discovery of diaphragmatic rupture, repair diaphragmatic rupture Unable to detect minor ruptures, invasive Huang et al. (21)
Radioisotope 99mTc-sulphur colloid Simple, quick, safe, and relatively noninvasive Radioactivity Benet et al. (19), Ajmi et al. (20)
Contrast-enhanced ultrasound Simple, quick, safe, non-radioactive Relying on ultrasound examination Mücke et al. (10)
VATS and methylene blue injection Able to detect minor ruptures, repair diaphragmatic rupture Invasive Fang et al. (24)
Pneumoperitoneum and indocyanine green Able to detect minor ruptures Invasive Yutaka et al. (26)
MRI Noninvasive Environmental factors limit the use of MRI Zenda et al. (23)

Each technique for detecting diaphragmatic rupture has some advantages and disadvantages. MRI, magnetic resonance imaging; VATS, video-assisted thoracoscopy surgery.

To date, most studies still involve radioisotope diagnostic techniques, such as labeling albumin using 99mTc (9,10,19,27). These techniques result in patients being exposed to radiation. These technologies come at a high cost and are not easily accessible. So, they are rarely used in clinical practice. However, methylene blue injection staining does not involve radiation exposure to patients, and it can be widely used at a low cost. Observing methylene blue stained pleural effusion is easier to implement than detecting the composition of tracer substances. It is particularly suitable for patients in the intensive care unit (ICU) who are limited by transport and examination. There are limitations to this approach. It has high specificity in detecting diaphragmatic rupture, but its sensitivity is unknown.

Treatment methods for patients with hepatic pleural effusion include diuretics, limiting salt intake, improving liver function, reducing peritoneal effusion generation, preventing fluid transfer to pleural cavity, pleural effusion drainage, pleural fixation, and liver transplantation (27). It is worth noting that although patients can reasonably tolerate large amounts of abdominal fluid, they cannot tolerate large amounts of pleural fluid, which can lead to respiratory failure and hypoxia in patients (28). An indwelling pleural catheter can reduce a large amount of pleural effusion (12). Multidisciplinary management involving respiratory medicine, hepatology and palliative care is essential to optimize patient-centered care.

Conclusions

Methylene blue injection staining is a supplementary method for the diagnosis of diaphragmatic rupture in patients with hepatic pleural effusion. It is suitable for areas lacking detection methods.

Acknowledgments

We did not apply any AI tools (e.g., ChatGPT, Bing) in the writing of a manuscript, production of images or graphical elements of the paper, or in the collection and analysis of data. The authors thank the patient who contributed to this study and acknowledge the clinical staff for their dedication. The authors thank the hospital medical research committee for its guidance.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-25-41/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-25-41/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-25-41/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. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Because the patient had passed away, written informed consent was obtained from the patient’s daughter for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

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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doi: 10.21037/acr-25-41
Cite this article as: Xing Z, Wang H. Application of methylene blue injection staining in the diagnosis of hepatic pleural effusion in patients with cirrhosis—a case report and literature review. AME Case Rep 2025;9:149.

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