Cytotoxicity, Antimicrobial and Antioxidant Activities of Apocarotenoid Rich Leaf Essential Oil of Maesobotrya Barteri Var. Barteri (Baill.) Hutch - Juniper Publishers

 

Technical & Scientific Research - Juniper Publishers

Abstract

Background: Maesobotrya barteri var. barteri (Phyllanthaceae) has analgesic, antimicrobial and antitussive applications in ethno-medicine. Essential oils and their constituents from herbs have also been utilized in the management of a good number of ailments in ethno-medicine. The phytochemical profile along with the corresponding cytotoxic, antimicrobial and antioxidant activities of the leaf essential oil have been investigated in the current research. The essential oil was obtained by hydro-distillation using an all-glass Clevenger apparatus. Identification and characterization were done using Gas Chromatography-Mass Spectrometry (GC/MS) while cytotoxicity assay was carried out by brine shrimp lethality test. The antimicrobial property was assessed by broth dilution method and antioxidant activity was evaluated with 2, 2-diphenyl-1 picrylhydrazyl radical (DPPH*) method.

Results: The essential oil contained a total of twenty-six compounds constituting 91.50 % of the total oil composition dominated with apocarotenoids comprising 49.4%, of which (E)-geranyl acetone (21.9 %) is the most abundant. Some other apocarotenoid constituents of the essential oil include β -ionone (8.9 %), 4-dehydro-β-ionone (5.4 %) and (E)-β-ionone (5.0 %). Brine shrimp lethality test revealed that the essential oil was non-toxic. The essential oil exhibited significant inhibition against bacterial and fungal strains at concentrations ranging from 1000 μg/mL to 62.5 μg/mL. M. barteri leaf essential oil exhibited significant antioxidant activity (% inhibition 90.04-84.73μg/mL) comparable to standard Ascorbic acid ((93.05- 90.40μg/mL) and butylated hydroxy anisole (92.60 - 90.68μg/mL) used for the assay.

Conclusion: The chemical composition of leaf essential oil of M. barteri could be responsible for the significant pharmacological applications of the plant in ethno-medicine and the phytoconstituent of the leaves essential oil of M. barteri is reported for the first.

Keywords: Maesobotrya barteri; Cytotoxicity; Antioxidant; antimicrobial; essential oil; apocarotenoids; (E)-geranyl acetone

Abbreviations: GC/MS: Gas Chromatography/Mass Spectrometry; FRIN: Forestry Research Institute of Nigeria; DMSO: Dimethyl sulfoxide; IC50: The half-maximal inhibitory concentration; DPPH: 2,2-diphenyl-1-picrylhydrazyl radical; LRI: Linear Retention Index; TIC: Total ion concentration in percentage; GC: Gas Chromatography; ANOVA: Analysis of variance; NIST: National Institute of Standards and Technology; MBL: M. barteri leaf; BHA: Butyl hydroxyanisole; DMBA: 7,12-dimethylbenz(a)anthracene

Background

Essential oils and their constituents since ancient times have been known for their oral, topical, aromatherapy properties and their wide range of applications in consumer goods such as soaps, detergents, cosmetics, pharmaceuticals, confectionery, perfumes, soft drinks, beverages and insecticides are due to their therapeutic importance and lower toxicity profile [1]. Its phytoconstituents play an important role as an ideal natural source for antimicrobial, antioxidant, anticancer and chemo preventive agents [2-6].

Maesobotrya barteri var. bateri (Baill.) Hutch (Phyllanthaceae) is a high forest flowering shrub commonly found in the rainforest region of West Africa and the most widely distributed Maesobotrya species in Nigeria [7,8]. Its fruits are edible, succulent and other parts are used for the treatment of diarrhea, dysentery, urethral discharge, cough and pain reliever [9,10]. Phytochemicals such as tannins, saponins, cardiac glycosides, deoxy sugar and terpenes have been reported in its leaf, stem bark and root extracts [11,12]. Its pharmacological relevance includes analgesic, antimalarial [13] and antimicrobial [12] activities. β-amyrin and oleanolic acid isolated from the aerial part of M. barteri

have been reported to exhibit antibacterial activity [14]. However, there is little or no report on the essential oil composition of M. barteri leaf in the literature notwithstanding its medicinal and nutritional importance in ethnomedicine. This has prompted us to undertake this study and we herein report the GC/MS analyses, antioxidant, antimicrobial and cytotoxicity activities of M. barteri leaf essential oil.

Methods

Plant Collection and Preparation

Fresh leaves of Maesobotrya barteri were collected along an open area in Utit Uruan, Akwa Ibom - Nigeria, in October 2018. The fresh leaves were identified and authenticated at Forest Research Institute of Nigeria (FRIN), Oyo State, Nigeria where a voucher specimen with herbarium number FHI 112780 was deposited in the FRIN herbarium.

Chemicals and reagents

n-Hexance and methanol were purchased from BDH general purpose chemicals and distilled prior to use. Dimethylsulphoxide (May & Bayer), England and 2,2-diphenyl-1-picrylhydrazyl (DPPH), ascorbic acid, butylated hydroxyanisole (BHA), Gentamicin and Tioconazole were obtained from Sigma Chemical Co. (St. Louis, MO).

Equipment and Apparatus

All-glass Clevenger, UV-Visible spectrophotometer (Unico1200 & Perkin Elmer lambda 25 models) and GC-MS (Agilent 7809A gas chromatography hyphenated with an Agilent mass detector).

Isolation of Essential Oils

Fresh Leaf of M. barteri (200.01g) were placed in an all-glass Clevenger-type apparatus according to British Pharmacopoeia specifications [15] and hydro-distilled for 3hrs. Essential oil (MBL) was collected using n-hexane and dried over anhydrous sodium sulfate, filtered and stored in a refrigerator at 4oC prior to analysis. The yield of the oil was calculated on a dry basis.

Identification and Quantification of the Essential Oil Constituents

The leaf essential oil of M. barteri were subjected to GC-MS analysis on an Agilent 7809A gas chromatograph hyphenated with an Agilent mass detector having split/split less injector interfaced to mass selective detector operating at 70 eV. Other experimental parameters were as follows: The ion source temperature was set at 200ºC within a mass spectral range of m/z 50-700 at a scan rate of 1428 amu/sec. GC column was equipped with an HP-5MS column with a length of 30 m, having an internal diameter of 0.25mm and a film thickness of 0.25 μm. The oven temperature was programmed as follows: initial temperature of 80ºC for 2min, increased at 10ºC/min to the temperature of 240ºC for 6min. Helium was utilized as the carrier gas at a flow rate of 1 mL/ min. Injection volume, linear velocity and pressure were respectively adjusted at 1.0 μL, 362 cm/s and 56.2 KPa. The oven temperature was set at 60ºC, held for 1 min to 180ºC for 3 min at 10ºC /min, the final temperature was 280ºC for 2 min at 10ºC/ min. Both injector and detector temperatures were fixed at 250ºC. Identification of the essential oil components was based on their linear retention indices as determined according to homologous series of normal alkane as well as by comparison of their mass spectral fragmentation patterns (NIST data/base/chemstation data system) with the data previously reported in the literature [16].

Brine Shrimp Lethality Test

Brine shrimp lethality test of the oil was conducted as described below: About 40 mg of shrimp’s eggs were sprinkled on shallow rectangular plastic into a larger compartment of two unequal compartments (70/30) containing seawater. The shrimp’s eggs were incubated for 48hrs in dark at room temperature. The shrimps (nauplii) were harvested on the smaller compartment exposed to a light source. The essential oil was dissolved in DMSO, and different concentrations were prepared using the serial dilution method (1000, 100 and 10 μg/mL). Ten nauplii were introduced in vials containing different concentrations of the oil. DMSO was tested as solvent control while doxorubicin was used as a reference standard. After 24hrs, the vials were examined against a lighted background and the average number of larvae that survived in each vial was determined [17]. Each experiment was carried out in triplicate and the IC50 (concentrations at which 50 % of nauplii were killed) were calculated from inhibition versus concentration graphs using Microsoft Excel package.

Antimicrobial Activity on the Leaf Essential Oil of M. Barteri

All microorganisms were clinical isolates obtained from the Department of Pharmaceutical Microbiology, University of Ibadan, Nigeria. Leaf essential oil of M. barteri was tested against seven strains of microorganisms consisting of four bacteria; two Gram-negative; Escherichia coli and Klebsiella pneumonia, two Gram-positive (Staphylococcus aureus and Bacillus subtilis) and three fungi (Candida albicans, Penicillium notatum and Aspergillus niger). Pour broth dilutions and surface plate methods were employed for antibacterial and antifungal activities, respectively [18]. The oil sample was prepared such that 1mL of the oil was regarded as 100 % concentration; 0.5mL into 0.5mL of DMSO to give 50 % concentration and 25 % concentration was obtained using serial dilution. DMSO was tested as solvent control, Gentamicin (10 μg/mL) as bacteria control and Tioconazole (0.7 mg/mL) as fungi control. All experiments were carried out in duplicates and observed zones of inhibition of growth were measured and recorded in millimeters (mm).

Antioxidant Activity of M. Barteri Leaf Essential Oil

Free radical scavenging activities of the essential oil and standards were determined by their ability to react with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH*) [15,19]. A methanol-DPPH* solution (0.1 mM) was prepared by dissolving 3.94 mg of DPPH* in 100 mL of methanol. The oil was dissolved in methanol to prepare five concentrations (1000, 500, 250, 125 and 62.5) μg/mL via serial dilution and was mixed with 2.0mL of DPPH* methanol solution (0.1 mM). The mixture was shaken robustly and left to incubate for 30 mins in the dark at room temperature. The absorbance at 517nm was recorded for sample using a GS UV-12, UV-Vis spectrophotometer. A control experiment was carried out applying the same procedure but without essential oil (DPPH* + Methanol) and the absorbance was recorded as Ac. The antioxidant activity of ascorbic acid and butylated hydroxy anisole (BHA) were used as standards for comparison. Each experiment was carried out in triplicates and the free radical scavenging activity of the essential oil was calculated as percentage inhibition (%I) using the formula:

Data Analysis

All results were conveyed as means ± standard deviation. Analysis of variance was used to determine any significant difference between groups using the statistical analysis software package GraphPad 5.0. Values with p<0.05 were regarded as significant. All graphs/charts were drawn with GraphPad 5.0.

Results

Phytochemical Profile of the leaf essential oil of >M. barteri

The hydro-distillation of M. barteri leaves gave pale yellow oil (0.51%) with a floral scent. GC-MS qualitative and quantitative data on the component of Leaf essential oil of M. barteri are shown in Figure 1 and summarized in Table 1. Twenty-six (26) compounds were identified representing 91.5% of the oil constituent. Apocarotenoids were the main constituents identified in the leaf essential oil (49.4%) followed by non-terpene derivatives (38.5%). Minor quantifications were observed in oxygenated monoterpenes (2.7%) and monoterpene hydrocarbon (0.9%). The most abundant compound was found to be (E)-geranyl acetone (21.9%). Other apocarotenoids identified in leaf essential oil include (E)-α-ionone (8.9%), 3, 4-dehydro-β-ionone (5.4%), (E)-β-ionone (5.0%), (E)-β-damascenone (3.8%), β-cyclocitral (1.5%), β-cyclohomocitral (1.2%), Safranal (0.9%) and dehydro- ar-ionene (0.8%). Other minor constituents of the essential oil include oxygenated monoterpenes [neo-dihydrocarveol (1.8%) and geranial (0.9%)] and monoterpene hydrocarbon [dihydrocamphene (0.9%)]. Some non-terpenes and derivatives identified were hexanal (6.4%), 2-pentylfuran (5.3%), (E, E)-2,4-decadienal (3.6%), (E)-2-undecenal (3.0 %), (E)-2-hexenal (2.3%), 6-methyl- 5-hepten-2-one (1.6%) and octanal (1.5%).

LRI - Linear Retention Index, TIC: Total ion concentration in percentage

Cytotoxicity Assay

The nauplii were exposed to leaf essential oil of M. barteri at different concentrations for 24hrs. The number of mortalities were calculated to determine the effectiveness of the essential oil. The cytotoxicity of M. barteri

essential oil and doxorubicin against nauplii (IC50) was 2822.46 μg/mL and 114.92 μg/mL respectively.

Antimicrobial Activity of the leaf essential oil of M. barteri

Experimental data obtained from the in vitro antimicrobial activity of M. barteri leaf essential oil is summarized in Table 2. The essential oil of M. barteri leaves exhibited significant antimicrobial activities with inhibitory zones of 22-34 mm against bacterial strains and 16-25mm against fungal strains when compared to the controls (Gentamicin: 40-45 mm and Tioconazole: 33 mm).

Antioxidant Activity

Results of the scavenging ability of leaf essential oil of M. barteri on DPPH* assay and IC50 values are summarized in Table 3, Figure 2. The percentage inhibition of the essential oil was concentration dependent.

The inhibitory zone was measured in millimeter, mm; N/A: Not applicable, (-): No inhibition, ± = Standard deviation.

MBL: leaf essential oil of M. barteri, BHA: Butyl hydroxyanisole, ± = Standard deviation.

Discussion

The reputed medicinal properties of M. barteri leaves in folk medicine might be due to the presence of relatively high amounts of apocarotenoids in the essential oil. (E)-geranyl acetone has been reported to possess strong antimicrobial activity [20-22]. β-Ionone has been shown to demonstrate potent anticancer activity both in vitro and in vivo and also suppresses DMBA-initiated mammary cancer in the rat [23]. α-ionone and β-ionone inhibited growth against algae [24] and are used in cosmetics such as perfumes [25]. Apocarotenoids also have wide applications in food, feed, nutritional, pharmaceutical and personal care. Their remarkable nutrition and health importance cannot be overemphasized [26-28].

Brine shrimp lethality assay is a method employed to evaluate the level of toxicity in plant extract and others based on the ability of the plant extract to kill a laboratory cultured larvae (nauplii) [17]. According to standard guidelines for determining the level of toxicity of samples, IC50 > 1000 μgmL−1 is considered nontoxic [29]. Thus, the essential oil in this study is non-toxic (IC50 of 2822.46 μg/mL) when compared to the doxorubicin (IC50 of 114.92 μg/ mL).

The antimicrobial activities of M. barteri leaves essential oil and the test organisms were concentration dependent. The essential oil showed significant antibacterial activity against both the gram-positive (23-28 mm) and gram-negative bacteria (26-34 mm). Generally, the gram-negative reference strains were more sensitive to M. barteri leaves essential oil than the gram-positive at all concentrations. Furthermore, E. coli and B. subtilis were more susceptible to the essential oil among the test strains by inhibitory zones of 26-33 mm and 22-28 mm respectively. With the antifungal assay, M. barteri leaves essential oil was most active against Candida albicans by a zone of inhibition of 20-25mm. Essential oils that was dominated with apocarotenoids such as (E)-geranyl acetone, α-ionone and β-ionone were reported to inhibit the growth of some microorganism [20-22,24]. The polar content such as apocarotenoids in the leaves essential oil may account for the strong inhibition of growth in the test microorganisms as polar compounds have been found to have better interaction with microorganisms - cell walls leading to their death [30].

DPPH* assay is considered a valid, accurate, easy and economic method to evaluate radical scavenging activity of antioxidants since the radical compound is stable [19, 31]. The mechanism of this assay follows the change in color of DPPH from purple to yellow as the radical is reduced by the antioxidant agent either by donating hydrogen atom or electron transformation of DPPH into its reduced form DPPH-H, becoming a stable diamagnetic molecule [30]. It was observed that the leaf essential oil of M. barteri exhibited significant scavenging ability at all concentrations with percentage inhibition between 90.04-84.73 (Figure 2 and Table 3), comparable to that of ascorbic acid (93.05-90.40) and BHA (92.60 - 90.68). Statistical analysis of the data subjected to analysis of variance (ANOVA) showed that there was significant difference between the leaf essential oil and the reference standard at p<0.05. Thus, the presence of apocarotenoids in the essential oil might be responsible for the antioxidant activity [32].

Conclusion

Twenty-six compounds were identified in the leaf essential oil of M. barteri. The essential oil is non-toxic and displayed significant antioxidant and antimicrobial activities. The essential oil is rich in apocarotenoid (49.4%). Apocarotenoid has been found to exhibit numerous biological activities in in-vitro and in-vivo experiments, including free radical scavenging, sunburn preventive, chemo preventive, antimicrobial, insect repellent and attractive effects. The essential oil of M. barteri displayed a significant free radical scavenging activity with percentage inhibition ranging from 90.04-84.73%. The leaf essential oil showed susceptibility against bacterial and fungal strains and the brine shrimp lethality test revealed that the essential oil was non-toxic. These results justify the medicinal applications of M. barteri in ethno-medicine.

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Substance Abuse and Partner Violence: The Case for Couples Therapy - Juniper Publishers

 

Addiction & Rehabilitation Medicine - Juniper Publishers

Abstract

Intimate partner violence continues to be a profound public health concern, with 25% of women and 10% of men report experiencing intimate partner violence in their lifetime. Many cases of intimate partner violence go undetected and untreated, however, identifying different ways of conceptualizing violence and alternative modalities of treatment may provide clinicians with the opportunity to intervene at higher rates. Given the men admitted to treatment for substance misuse problem report high rates of partner violence, this setting may provide an important point of contact for identification and treatment. Research using Behavioral Couples Therapy address non-severe forms of violence within a substance abuse treatment setting with promising outcomes. Future research is needed to identify the best technique to manage more severe forms of violence and in which settings.

Keywords: Clinical psychology; Substance abuse; Intimate partner violence; Behavioral therapy; Couples therapy

Abbreviations: IPV: Intimate partner violence; BCT-SUD: Behavioral Couples Therapy for Substance Use Disorders; SAMHSA; Substance Abuse and Mental Health Services Administration

Introduction

Intimate partner violence (IPV) remains a tremendous public health concern which transcends age, gender, ethnicity, and social standing [1]. National surveys of couples reveal 25% of women and 10% of men are victims of intimate partner violence [2]. As alarming as these statistics seem, they pale in comparison to rates of partner violence reported among men admitted into substance abuse treatment [3]. As these cases often go undetected and untreated, the challenge for clinicians and researchers alike is to identify different ways of conceptualizing violence and consider alternative modalities of treatment.

What is IPV?

A challenge when investigating partner aggression has been the lack of consensus on the definition. Intimate partner violence and family violence, including the threat of violence, can be conceptualized as violence that occurs between the partners of a romantic relationship [4]. A number of theories have been proposed to explain IPV including feminist, family violence, and psychopathology. The feminist perspective understands IPV through the historical traditions of male dominance and is largely concerned with power and control [5,6]. The feminist perspective states violence and aggression are indicators of social power, and that IPV is a result of disparity in the perceived equality of the genders [7]. According to family violence theory, familial stressors may foster a conflictual environment, in which violence is used as a method of conflict resolution [8]. Finally, the psychopathology perspective emphasizes individual problems, including emotional deregulation, personality disorders, and early life experiences [7]. In fact, 80-90% of male-female IPV cases involve and assaulter with a personality disorder, compared to the 10-15% of individuals in the general population with a personality disorder [7].

It is important to note that IPV is often conceptualized as a homogenous phenomenon, when in fact, it encompasses a wide range of physically aggressive behaviors which may differ along dimensions such as:

a. Type and severity of aggression.

b. Frequency.

c. Emotional and physical impact [7].

In an effort to more accurately capture types of partner aggression, Johnson [9] developed a control-base typology, describing three types of IPV that appear to be conceptually and etiologically distinct. Intimate Terrorism, is characterized by severe male-to-female physical aggression (e.g., punching, threatening with weapons), with less severe female-to-male violence occurring during these episodes as a form of self-defense (i.e., Violent Resistance). In cases of Intimate Terrorism, female partners are at an increased risk of physical injury and there is a heightened fear of the male partner. In this case, the goal of the aggressor is to exert power and control over the partner. Violent Resistance typically occurs in response to a partner’s violent and controlling behavior (e.g., Intimate Terrorism); this type is violent but not used as a form of control and may be best thought of as defensive responding. Situational Couple Violence is characterized by bidirectional partner aggression, which is mild to moderate in severity and is the result of an escalation in conflict. Situational Couple Violence is a method used to exert power or control, nor is it used to instill fear. Situational Couple Violence is likely to be akin to violence reported among substance misusing clients, whereas Intimate Terrorism more closely resembles the violence found in clinical samples.

Treatment Options

Treatment-as-usual: standard substance abuse treatment

One option for identifying IPV involves training staff to identify and assess for partner violence and refer those patients to domestic violence intervention programs (i.e., coordinated response approach). Given the prevalence of IPV among men entering substance abuse treatment, these programs may be an important point for identification and referral. However, research indicates substance abuse treatment providers rarely make referrals to batterers treatment due to the lack of formal assessment of IPV during intake and treatment and/or use of inadequate measures [10]. Consequently, the lack of formal IPV screening during intake and treatment results in these issues going undetected and inappropriately addressed. Given the link between substance use and violence, it is plausible that engagement in substance abuse treatment and decreased substance use may result in reduced partner aggression. However, substance abuse clients have high rates of relapse, and so this decrease in partner aggression may be contingent on the client’s ability to remain abstinent-thus, this approach is inherently flawed. Moreover, referral to domestic violence treatment programs (i.e., batterers’ treatment) presents two important challenges:

a. Existing research suggests that clients rarely followthrough and engage with domestic violence prevention programs and those that do, tend to drop out prematurely.

b. The evidence for the effectiveness of batterers’ programs in reducing partner violence has been mixed [11]. These programs tend to be tailored to the most severe forms of violence and do not take the different forms of IPV into account [11]. As a result, domestic violence treatment is not suitable or a good fit for many offenders.

Behavioral couples therapy for alcoholism and substance abuse: effects on IPV

Partner-involved conjoint therapies are among the most controversial treatment approaches. Critics argue that addressing IPV in a relational context will place female victims in the role of having to manage their partner’s violent behavior [12]. Critics also argue that conjoint approaches encourage honest and open disclosure, which, in turn, could lead to conflict in therapy sessions that could escalate to violence outside of therapy. However, given the interactional and bidirectional nature of some types of violence, carefully screened and controlled partner-involved treatments may have advantages for couples who engage in non-severe forms of IPV [13].

Couples therapy may allow for a more effective conceptualization of the IPV, as treatment focuses on violence reduction, encouraging partners to discuss emotionallycharged topics, and fostering adaptive communication [13]. Partner aggression often occurs in the context of disagreements between partners and is often mutual and bidirectional [13]. This escalation in conflict frequently results in a vicious cycle, in which one behavior serves to reinforce the other in a continuous feedback loop. Thus, addressing the reciprocal nature of violence may provide an opportunity to alter the interaction patterns that precede it and learn healthier ways of resolving conflict. Because relationship distress is a powerful predictor of partner aggression [13], improvements in relationship functioning should reduce the likelihood of IPV.

Behavioral couples therapy for alcoholism and substance abuse: effects on IPV

Behavioral Couples Therapy for Substance Use Disorders (BCT-SUD) is a conjoint treatment for alcohol and drug abuse with extensive empirical support for its clinical and cost effectiveness. According to “Substance abuse treatment and family therapy” [14] the US government regulatory panel, titled Substance Abuse and Mental Health Services Administration (SAMHSA), recognizes BCT-SUD as an evidence-based treatment. The focus of BCT is twofold:

a. Improve relationship functioning.

b. Reduce or eliminate substance abuse.

BCT-SUD posits that problems within the relationship can serve as a trigger for substance use and that problematic substance use negatively impacts relationship functioning. As a result, the couple is caught in a cycle in which each problem serves as both the antecedent and consequence, and continuously reinforces the other. Partners engaged in BCTSUD are taught communication and conflict resolution skills for managing emotional disagreements and conflict (for a review, see Fals-Stewart et al. [15]). Nonsubstance-abusing partners are also taught skills to increase safety when faced with a situation where a relapse to drugs, violence, or both are likely. It is important to note that BCT does not rely on abstinence as the mechanism of action for nonviolence; thus, BCT is designed to decrease IPV even in the event a relapse occurs.

Several noncontrolled studies have examined the effects of BCT on IPV prevalence and frequency among alcohol and drugabusing men and their nonsubstance-abusing female partners [16,17] and reported up to a 60% decrease in IPV prevalence in the year following treatment compared to baseline levels. O’Farrell and Fals-Stewart [18-20] collected a sample of drugabusing couples with and without a history of IPV and found that significantly smaller proportion of drug-abusing couples who received BCT reported episodes of IPV compared to those who participated assigned to a treatment-as-usual condition.

Conclusion

Partner violence remains a tremendous public health concern. Given the rates of IPV reported among men admitted to treatment for substance misuse problem, this setting may serve as an important point of contact for identification and treatment. The results of the studies listed above reveal the promise BCT holds as an intervention to address non-severe forms of violence within a substance abuse treatment setting. However, additional research is needed to determine how best to manage more severe forms of violence and in which settings.

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Understanding The Acute Interventions for Complicated Pleural Effusions - Juniper Publishers

 

Pulmonary & Respiratory Sciences - Juniper Publishers

Abstract

Pleural effusion affects approximately 1.5 million individuals in the U.S. annually. A significant subset of these cases evolves into complicated parapneumonic effusions due to bacterial infections, intense inflammation, or other causal factors, presenting considerable diagnostic and therapeutic challenges. If untreated, the condition’s sequential progression can culminate in restrictive respiratory dysfunction. This review examines the diverse interventions available for diagnosing and treating complicated pleural effusions. The therapeutic spectrum ranges from minimally invasive procedures such as thoracentesis and Intrapleural Enzymatic/Fibrinolytic Therapy (IPET) to surgical interventions, including Video-assisted Thoracoscopic Surgery (VATS) for pleurodesis and pleurectomy/decortication, and open pleurectomy/decortication. Notably, the combined use of agents in IPET presents a significant advancement, especially for patients unsuitable for surgery. Furthermore, VATS emerges as a promising, less invasive surgical alternative, and the role of pleurectomy/decortication in managing malignant mesothelioma becomes more pronounced, offering advantages over other surgical modalities. The diagnostic and therapeutic landscape for complicated pleural effusions is vast and continues to evolve, with an increasing emphasis on minimizing invasiveness and optimizing patient outcomes. As clinical approaches diversify and improve, ensuring patient-centric care becomes paramount. The future of this domain rests on refining current practices and further investigating newer interventions to elevate patient outcomes.

Keywords: Pleural Effusion; Parapneumonic Effusion; Thoracentesis; Video-assisted; Pleurectomy

Abbreviations: VATS: Video-assisted Thoracoscopic Surgery; IPET: Intrapleural Enzymatic/Fibrinolytic Therapy; LDH: Lactate Dehydrogenase; CT: Computed Tomography; EPP: Extrapleural Pneumonectomy; TPA: Tissue Plasminogen Activator; DNase: Deoxyribonuclease; rTPA: Recombinant Tissue Plasminogen Activator; P/D: Pleurectomy/Decortication; MIST: Multicenter Intrapleural Sepsis Trial

Introduction

Pleural effusion, characterized by the accumulation of fluid between the parietal and visceral pleura within the pleural cavity [1], can become a complex condition when infected by bacteria or other microorganisms, leading to a complicated parapneumonic effusion with positive Gram stain or significant inflammation [2,3]. As the most prevalent among all pleural diseases, pleural effusion affects approximately 1.5 million patients annually in the United States, with parapneumonic effusion developing in about 20% to 40% of hospitalized pneumonia patients, accounting for nearly 1 million cases yearly [1,2]. The progression of parapneumonic effusion encompasses distinct stages: the exudative stage, marked by fluid accumulation in the pleural space; the fibrinopurulent stage, characterized by the deposition of fibrin clots and fibrin membranes within the pleural cavity; and the organizing stage, during which fibroblasts transform fibrin membranes into a thick, nonelastic pleural peel, leading to trapped lung and restrictive respiratory dysfunction [2].

Clinical presentation of parapneumonic pleural effusion includes chest pain, cough, fever, and systemic manifestations. Physical examination often reveals signs of volume gain, reduced tactile vocal fremitus, dullness on percussion, shifting dullness, and diminished or absent breath sounds [1,2,4]. Chest radiographs play a crucial role in confirming the presence of an effusion. At the same time, further analysis of pleural fluid involves a battery of commonly performed tests, including measurement of fluid pH, protein, albumin, LDH (lactate dehydrogenase), glucose, triglycerides, cell count differential, gram stain, culture, and cytology [1,4]. The management of parapneumonic pleural effusion may encompass various approaches, such as therapeutic thoracentesis, intrapleural enzymatic/fibrinolytic therapy, video-assisted thoracoscopic surgery, or open surgery. This narrative review aims to provide an informative overview of the current concepts related to the early diagnosis and multidisciplinary management of parapneumonic pleural effusion, emphasizing the significance of timely and comprehensive care for affected patients.

Epidemiology, Etiology & Pathophysiology

The mortality rate from thoracic empyema remains high, ranging between 6%-24%. Pleural infection develops in 65,000 patients annually in the United States and the United Kingdom. A significant proportion of pleural space infection complicates community or hospital-acquired pneumonia. However, a proportion of pleural space infection results from iatrogenic causes; it is also known that pleural infection may develop without pneumonia, so-called primary empyema [5,6]. A significant proportion of pleural space infection presents as complications in the community or hospital-acquired pneumonia. Other causes include penetrating chest trauma, thoracic surgery, and esophageal rupture. Independent risk factors for empyema development include age under 60 years old, poor oral hygiene, disorders with a predisposition to aspiration (seizure, alcoholism, central nervous system disease), IV drug misuse, diabetes, cardiovascular disease, liver cirrhosis, other immunocompromised states (HIV infection, malignancy) [7,8].

A three-stage classification of parapneumonic effusion (exudative, fibrinopurulent, and organizing) was proposed in 1962. Early observations suggested that it took 2 to 3 weeks for the early exudate to become purulent [6]. However, the time to progress from one stage to another is highly variable [7-9]. Exudative stage initial bacterial infection causes an acute inflammatory response between the pulmonary parenchyma and visceral pleural. Proinflammatory cytokines cause increased capillary permeability leading to an influx of neutrophil-rich fluid into the pleural space. This exudative fluid is usually free-flowing. Fibrinopurulent and loculated is the second stage. Without appropriate treatment, the effusion can become complicated via the deposition of fibrin clots and membranes, resulting in isolated fluid collections in the pleural space [6-9]. At this stage, bacteriology usually becomes positive, and the effusion warrants antimicrobials and drainage. The last stage is chronic organizational if not drained; fibroblasts merge to form a thick pleural peel between the visceral and parietal pleura. This peel can ultimately encase the underlying lung parenchyma and complicate the clinical course by inhibiting adequate gas exchange, trapped lung, or chronic forms of empyema [9,10].

Clinical Presentation & Diagnostic Approach

The clinical presentation of complicated pleural effusions can vary widely and often depends on the underlying etiology and the extent of pleural involvement. Patients may present with symptoms such as dyspnea, pleuritic chest pain, cough, fever, and general malaise [11-14]. On physical examination, decreased breath sounds, dullness to percussion, and decreased tactile fremitus may be observed over the affected area. In large or loculated effusions, there may be signs of respiratory distress, such as increased respiratory rate, use of accessory muscles, and cyanosis [11-15]. The diagnostic approach involves a thorough medical history, physical examination, and imaging studies. Chest X-ray is often the initial imaging modality, which may reveal pleural effusion and thickening. Computed tomography (CT) scan provides more detailed information and can help identify loculated effusions, pleural masses, or signs of infection [13,14]. Thoracentesis is a crucial diagnostic procedure, allowing for pleural fluid analysis.

Laboratory analysis of pleural fluid includes evaluation of cell count, protein, lactate dehydrogenase (LDH), glucose, pH, and cytology. An elevated white blood cell count, low glucose, elevated LDH, or positive cytology may indicate infection or malignancy. If infection is suspected, pleural fluid culture and Gram stain should be performed. In some cases, further imaging studies like ultrasound or pleural biopsy may be necessary to establish the underlying cause [11-13]. The management of pleural effusions is largely based on the underlying cause. Based on fluid chemistry, pleural effusions are broadly categorized as transudates or exudates. This classification helps guide further evaluation to determine the underlying etiology. Acute interventions for complicated pleural effusions depend on the specific etiology. Therapeutic thoracentesis can be performed for symptomatic relief and diagnostic purposes. Drainage of large effusions may require the placement of a chest tube to facilitate fluid removal and lung re-expansion [13-15].

In cases of empyema, a more aggressive approach may be necessary, such as video-assisted thoracoscopic surgery (VATS) or open thoracotomy with decortication. Antibiotics are initiated promptly in cases of infection, and appropriate broad-spectrum coverage should be considered until the causative organism is identified. In some instances, pleurodesis may be performed to prevent fluid re-accumulation and manage recurrent pleural effusions. In conclusion, the clinical presentation of complicated pleural effusions can be diverse, with prominent respiratory symptoms [12-15]. A comprehensive diagnostic approach, including imaging studies, pleural fluid analysis, and possibly biopsy, aids in determining the underlying cause. Acute interventions depend on the specific etiology and may involve therapeutic thoracentesis, chest tube placement, surgical interventions, and appropriate antimicrobial therapy [15].

Therapeutic Thoracentesis & Thoracocentesis

Indications

The indications for thoracentesis are relatively broad, including diagnostic and therapeutic clinical management. Thoracentesis should be performed diagnostically whenever the excessive fluid is of unknown etiology. It can be performed therapeutically when the fluid volume is causing significant clinical symptoms. Typically, diagnostic thoracentesis is a small volume (single 20cc to 30cc syringe). Unless the etiology is evident, a first-time thoracentesis should have a diagnostic sample collected for laboratory and pathology analysis. Typically, therapeutic thoracentesis is a large volume (multiple liters of fluid). A small sample of a large volume thoracentesis should be sent for analysis when the etiology of the fluid is unknown, or there is a question of a change in the etiology (e.g., new infection, decompensated chronic condition). If the fluid volume is anticipated to reaccumulate quickly, a drain is often left in place to collect this fluid. This often is seen in trauma (e.g., hemothorax), cancer (e.g., malignant effusion), post-operatively (e.g., cardiothoracic post-operative healing/inflammatory conditions), and end-stage metabolic conditions with the systemic excessive colloid leak (e.g., cirrhosis or malabsorption syndromes). A fluid collection that is believed to be infected should be drained to eliminate the source of infection and/or reservoirs of the infection [16,17].

Contraindications

There are no absolute contraindications. Relative contraindications include any condition that prohibits safe patient positioning, uncontrollable coagulation deficits through medications/iatrogenic or intrinsic, or conditions in which the potential procedure complication outweighs the benefits [17].

Technique or treatment

The preferred site for the procedure is on the affected side in either the midaxillary line if the procedure is being performed in the supine position or the posterior mid-scapular line if the procedure is being performed in the upright or seated position. Bedside ultrasound should be used to identify an appropriate location for the procedure. Placing the patient in the upright seated position and using bedside ultrasound can aid in identifying fluid pockets in patients with lower fluid volumes. Prep and drape the patient in a sterile fashion. Cleanse the skin with an antiseptic solution. Administer local anesthesia to the skin (25-gauge needle to make a wheal at the skin’s surface) and soft tissue. After administering the local anesthetic, use a more significant 20- or 22-gauge needle to infiltrate the tissue around the rib, marching the needle tip just above the rib margin. Insert the needle or catheter attached to a syringe or the prepackaged catheter directly perpendicular to the skin.

If using a catheter kit, it may be helpful to make a small nick in the skin using an 11-blade scalpel to smoothly advance the catheter through the skin and soft tissue. Apply negative pressure to the syringe during needle or catheter insertion until a loss of resistance is felt and a steady fluid flow is obtained. This is paramount to detect unwanted entry into a vessel or other structure. Advance the catheter over the needle into the thoracic cavity. After you collect sufficient fluid in the syringe for fluid analysis, either remove the needle (if performing a diagnostic tap) or connect the collecting tubing to either the needle or the catheter’s stopcock. Drain larger volumes of fluid into a plastic drainage bag using gravity feed or serial syringe draw with a three-way stop-cock. After draining the desired amount of fluid, remove the catheter and hold pressure to stop bleeding from the insertion site [18].

Clinical significance

Thoracentesis may relieve pressure from fluid on the lungs treating symptoms such as pain and shortness of breath. Evaluation of the fluid removal may determine the underlying cause of excess fluid in the pleural space [16,17].

Complications

Complications include bleeding, pain, and infection at the needle entry point. If the approach is too high in the intercostal space, damage to the coastal vasculature and nerve injury is possible. If too much fluid is removed or if the fluid is removed too rapidly (e.g., using negative pressure chambers), re-expansion (aka post-expansion) pulmonary edema may occur. Removal of significant fluid volumes may also induce vasovagal physiology. If the procedural needle/catheter is passed through diseased tissue before entering the chest cavity, that process can be extended into the chest space. For example, passing the needle through a thoracic or pleural tumor can seed the thoracic cavity, or passing the needle through a chest wall abscess or otherwise infected tissue can result in empyema. If the insertion site is too low, splenic and hepatic puncture can occur. Except for localized pain from the actual procedure, pneumothorax is the most common complication reported in 12-30% of cases.

Pre and post-chest radiographs are appropriate routine practice. Rare cases of retained intrapleural or intrathoracic catheter fragments have been reported. This is typically only seen when a catheter over trocar technique is used. To aid in repositioning, the catheter is advanced back over the trochar resulting in tear and failure of the catheter integrity [16-19]. Documenting the presence and location of lung sliding before the procedure is essential. (Best examined with a greater than 5 MHz vascular probe). The disappearance of lung sliding or B-lines suggests the interval development of a pneumothorax. Indications of chest tube placement to manage the pneumothorax following thoracentesis are 1. large pneumothorax, 2. progressive, 3. symptomatic pneumothorax. The occurrence of pneumothorax in mechanically ventilated patients should be managed with chest tube placement [16-19].

Intrapleural Enzymatic/Fibrinolytic Therapy

Apart from antibiotics, surgery is an effective treatment for separating fibrous formation and potentiating fluid drainage. However, because of the mortality, it is still a controversial approach, especially for patients with comorbidities. Intrapleural fibrinolysis, on the other hand, has increasingly gained interest from physicians by activating plasmin to lyse fibrinous septations and turning back the balance between fibrin activators and inhibitors. Fibrinolytic therapy, including streptokinase, urokinase, alteplase, recombinant tissue plasminogen activator (TPA), and Deoxyribonuclease (DNase), is intended to improve drainage and reduce the need for invasive interventions and therefore likely decrease mortality. Patients diagnosed with complicated pleural effusion or empyema, who are also unsuitable for operative management, are indicated with rTRPA and DNase [20].

Although First Multicenter Intrapleural Sepsis Trial (MIST-1) conducted in infected pleural effusion shows that there was no difference between Intrapleural fibrinolytic agents (Streptokinase) and placebo in improving outcomes, in MIST-2, combined treatment with TPA and DNase increased drainage of infected fluid compared with placebo, TPA alone and DNase alone. More specifically, in a total of 193 patients randomized with (1) double placebo, (2) TPA plus placebo, (3) DNase plus placebo, and (4) TPA plus DNase, the TPA/DNase group resulted in a significant reduction in Chest Radiography, lower referral rate for surgery and shorter on average hospital stays than the three remaining groups [21,22].

In a cohort study in Loculated pleural effusion by Saleh Abu-Daff et al. [23] all patients with pleural effusions that showed no response to 24-hour drainage, including emphysema, complicated parapneumonic effusions (CPE), and haemothorax or malignant effusions were given Streptokinase or TPA. The procedure’s success was based on clinical + radiological improvement without further requirements. At the same time, the failure to resolve loculated pleural effusion or a complication necessitating resuscitation was defined as failure outcomes. In a total of 227 cases, 72% (163/227) patients had emphysema or CPE, and the overall success rate was 80% (181/227) in which empyema and CPE patients had a success rate of 85% (138/163). Streptokinase therapy had a success rate of 73,1%, while patients receiving t-PA had a success rate of 81,2% which was not statistically different [21]. Saleh Abu-Daff et al. also demonstrated that the major complication was bleeding, which occurred in 15 patients, 8 of whom needed blood transfusion for at least 1 unit of packed red blood cells, and 3 required emergency thoracotomies to control bleeding.

Other minor adverse effects were mentioned and easily manageable, including pain (19/227) which required analgesic requirement, shortness of breath in (8/227) patients who needed to be increased oxygen requirement, and fever (9/227), which required antipyretics [23]. When it comes to contraindications of intrapleural fibrinolysis, it is stated in MIST-2 that all patients who had a known sensitivity to DNase or TPA, a history of coincidental stroke, major bleeding or trauma, 5-day post-operation of major surgeries, or previous pneumonectomy were excluded from their study. These criteria can be a reference source to consider contraindication factors for patients before this procedure. Moreover, patients under 18 years or pregnant or lactating are also inappropriate for this therapy [23].

Video-assisted Thoracoscopic Surgery (VATS): Pleurodesis

Video-assisted thoracic surgery (VATS) for pleurodesis is a minimally invasive surgical procedure for managing recurrent pleural effusion or pneumothorax. Pleurodesis is a medical intervention aimed at creating adhesions between the two layers of the pleura (the lining of the lungs) to prevent the recurrence of fluid or air accumulation in the pleural space. During the VATS procedure, the patient is placed under general anesthesia, and small incisions (usually 0.5 to 1.5cm) are made in the chest wall. A thoracoscope, a tiny camera attached to a thin, flexible tube, is inserted through one of the incisions, providing the surgeon with a visual image of the pleural cavity on a video monitor. Through other incisions, surgical instruments are introduced to perform pleurodesis. The surgeon can use agents like talc, doxycycline, bleomycin, or other sclerosing agents to create inflammation and adhesions between the pleural layers, promoting the lung’s adherence to the chest wall [24].

The most common indication for pleurodesis is a malignant pleural effusion, typically refractory. Other indications for pleurodesis are recurrent pneumothorax and recurrent pleural effusions. While there are many management options for treating these pleural diseases, the decision to proceed with pleurodesis should be carefully undertaken after discussion with the patient and reviewing expectations from the procedure. Medical pleurodesis is a preferred approach for patients [25]. Indications for mechanical pleurodesis are similar to chemical pleurodesis, with the added benefit of treating the underlying cause if present during the same procedure. For example, the simultaneous inspection and resection of subpleural blebs and bullae could be the source of recurrent pneumothorax [26].

In recent years, there has been a growing tendency to treat patients with pneumothorax using video-assisted thoracoscopic surgery (VATS) to achieve resection of the bullae or blebs and achieve pleurodesis, either through local abrasion of the parietal pleura or localized apical pleurodesis. However, this procedure is expensive and requires general anesthesia and (usually) double-lumen tracheal intubation. Also, the recurrence rate varies wildly, depending on the identification and subsequent ablation of blebs, according to Naunheim et al. The use of VATS or conventional thoracoscopy and pleurodesis, or thoracotomy, is dependent upon several factors, and there is no precise technique of choice. VATS would be recommendable in young patients with recurrent pneumothorax, combined with some technique to induce pleural symphysis (usually mechanical pleural abrasion or apical talc pleurodesis) [24,27].

VATS pleurodesis showed a quantitative advantage, and it may be concluded that the average hospitalization when applying the VATS pleurodesis was shorter. Abouzgheib et al. mentioned in their retrospective study that the average duration of hospitalization was 9 days after VATS pleurodesis. Likewise, Fortin et al. mentioned that the hospitalization period was 4-7 days for VATS pleurodesis. Troter et al. and Mitrofan et al. mentioned that the hospitalization period for VATS pleurodesis with talc was 7-10 days [28].

Video-assisted Thoracoscopic Surgery (VATS): Pleurectomy/Decortication

VATS pleurectomy is performed under general anesthesia, single-lung ventilation, and double-lumen endotracheal ventilation with the patient in a lateral decubitus position. The incision is made in the 5th intercostal space at the anterior axillary line, approximately 4cm long. An incision for the camera trocar is occasionally made in the 7th intercostal space at the midaxillary line for approximately 1cm. The parietal pleura is separated using scissors, with the pleura on the diaphragm left intact. After resection, electrocautery is used to achieve homeostasis, and a 28-Fr chest tube is inserted and connected to a water seal system for drainage post-procedure [29]. One of the main indications for VATS Pleurectomy is primary spontaneous pneumothorax and recurrent spontaneous pneumothorax [30,31]. VATS permits the entire lung’s observation, identifying blebs and bullae and resecting these diseased areas [32]. Another upcoming indication for this procedure is palliative pleurectomy for malignant mesothelioma [31].

The long-term prognosis is excellent, with low recurrent rates for primary and secondary spontaneous pneumothorax with VATS procedures [33]. A study done by Nathan et al. concluded that there was a 2.5% recurrence among 39 patients following total thoracoscopic pleurectomy [34]. Another study by Leo et al. showed the recurrence rate difference between VATS-limited pleurectomy among 54 patients and wide pleurectomy and open pleurectomy in 36 patients. The recurrence rates were 4% and 0%, respectively [35]. VATS procedures generally have been found to have a low incidence of complications. The most common complication of a pleurectomy is dense adhesions in the chest cavity [29]. A rare complication is the formation of neopleura, leading to recurrence. Pleurectomy can also damage the sympathetic chain at the T2-T4 level, which can cause palmar anhidrosis and compensatory contralateral hyperhidrosis [36].

Open Surgery

Pleurectomy/decortication (P/D) surgery is a two-part procedure. Pleurectomy involves opening the chest cavity and removing the pleural lining around the lung and other cancerous tissues. The decortication then removes any visible tumor masses from the surface of the lung and the rest of the chest area. Pleurectomy/decortication can extend survival and significantly increase the quality of life for eligible patients, especially when it’s part of a multimodal treatment approach that includes chemotherapy, radiation therapy, immunotherapy, or other emerging treatment options [37]. The chest cavity is entered extrapleurally. A deliberate dissection is performed, mobilizing the pleura from the chest wall. A self-retaining Finochietto retractor is used to spread the ribs slowly to avoid fracturing the ribs. Blunt hand dissection is performed in the extrapleural plane between the parietal pleura and endo thoracic fascia to take down the parietal pleura intact. We place multiple sponge packs to help tamponade and limit blood loss. Moving systematically and organized throughout the chest to limit blood loss is paramount.

Once the parietal pleura are mobilized, the dissection is continued removing the mediastinal pleura. All mediastinal structures are carefully preserved. The superior vena cava, azygous trachea, left on the right side. The right main bronchus vein and esophagus are carefully protected, and on the left side, the esophagus, aorta, and vagus nerve, including the recurrent nerves, should be preserved. The phrenic nerves are identified and preserved whenever possible when the diaphragm is not resected. It es also essential to appreciate the location of the internal mammary vessels, which can inadvertently be injured and be a source of significant blood loss. If they are involved in a tumor, proper control of the vessels should be achieved and divided [38]. If the tumor involves the diaphragm, partial or complete resection is performed. Whenever possible, the peritoneal membrane is preserved.

Although every effort is made not to enter the peritoneum, this is often very difficult due to the thin nature of the diaphragm at the central tendon, and sometimes the tumor involves near the total thickness of the diaphragm [38]. With the parietal pleurectomy now complete, the decortication and resection of the visceral pleura are performed. The anesthesia team is made aware of this transition as this requires a change in ventilation management. A second ventilator is connected to the affected side, and the lung is inflated with room air at high tidal volumes (8-10 L/min). A ten-blade scalpel cuts vertically through the tumor and past the visceral pleura. This is perhaps the most crucial step, as the visceral pleura must be appropriately identified and removed. The tumor, visceral pleura, and parietal pleura are then stripped off the lung using a combination of blunt and sharp dissection.

Many techniques are used to achieve this, including suction dissection, ultrasound, or plasma, in order to lift the tumor layer off the lung. Air leaks can be large and are expected during this portion of the procedure. Packing with wet gauze or lap pads is helpful to reduce the air leak and encourage the formation of a coagulum on the surface of the lung. Due to the tedious nature of this dissection, it is essential to continue in a patient, systematic and organized fashion. The dissection is continued in the fissures removing the visceral pleura on both sides towards the pulmonary arterial branches. Any lymph nodes encountered in the fissure are removed for histológicas examination [38]. We next perform the mediastinal lymph node dissection. We routinely remove lymph nodes from levels 4,7 and 9. It is not unusual to find internal mammary, costophrenic, or nodes in the posterior intercostal space, which are also removed. We also remove any other nodes that appear abnormal during the dissection. Suppose the patient is a candidate for EPP.

In that case, mediastinal lymph node dissection is conducted earlier with a frozen section after the extrapleural mobilization of the parietal pleura before the final decision. If there is any concern for metastatic disease in any lymph node, we proceed with PD and not EPP in these candidates [38]. Complications that may occur include infection, bleeding air leak, pneumonia, cardiac complications, respiratory failure, and post-operative pain. A pleurectomy has a risk of failure with a mortality rate of around 3.1%. Macroscopic complete surgical resection with curative intent of malignant mesothelioma includes extrapleural pneumonectomy (EPP) and pleurectomy and decortication (P/D).

Various studies have demonstrated decreased short-term mortality with P/D compared to EPP and improved quality of life and safety in the elderly without increased morbidity and mortality. P/D was defined as parietal and visceral pleurectomy to remove all gross tumors without diaphragm or pericardial resection. Extended P/D (EPD) was defined as parietal and visceral pleurectomy to remove all gross tumors with the diaphragm and/ or pericardium resection [37,38]. Of the 2 types of surgeries for MPM, pleurectomy/decortication (P/D) is a lung-sparing approach that is less invasive than EPP. However, there is concern regarding local control. Cao and coworkers reported a systematic review and meta-analysis of P/D and EPP for MPM, stating that P/D is performed with lower morbidity and mortality outcomes and comparable long-term survival outcomes to EPP [38,39].

Conclusion

The discussed literature provides a comprehensive overview of various aspects of pleural effusion and its management, mainly focusing on parapneumonic effusion. Pleural effusion, characterized by fluid accumulation between the pleural layers, can become complex when infected by microorganisms, leading to a complicated parapneumonic effusion. This condition affects many patients annually, with clinical presentations involving various respiratory and systemic symptoms. The three-stage classification of parapneumonic effusion (exudative, fibrinopurulent, and organizing) highlights the progression and potential complications of the condition. Diagnostic approaches, including imaging studies, pleural fluid analysis, and sometimes biopsy, aid in identifying the underlying cause and guiding appropriate management strategies.

Therapeutic thoracentesis, intrapleural enzymatic/fibrinolytic therapy, video-assisted thoracoscopic surgery (VATS), and open surgery are discussed as potential interventions for pleural effusion management. Each approach has indications, contraindications, techniques, clinical significance, and potential complications. VATS procedures, including pleurodesis and pleurectomy/decortication, offer minimally invasive surgical options with potential benefits regarding recurrent pleural effusion prevention and improved quality of life. The literature underscores the importance of a multidisciplinary approach and timely intervention for managing parapneumonic pleural effusion. The management choice should consider individual patient factors, the underlying cause of the effusion, and potential benefits and risks associated with each treatment option. Overall, this narrative review provides valuable insights into the current concepts and practices in diagnosing and managing parapneumonic pleural effusion, highlighting the significance of comprehensive care for affected patients.

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