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Respirology (Carlton, Vic.) Oct 2019Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion... (Review)
Review
Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion with loculations, pleural thickening and even frank empyema, all of which may have a lasting effect on lung function. The pathogenesis is a combination of true pleural infection and an effusive hypersensitivity reaction, compartmentalized within the pleural space. Diagnostic thoracentesis with thorough pleural fluid analysis including biomarkers such as adenosine deaminase and gamma interferon achieves high accuracy in the correct clinical context. Definitive diagnosis may require invasive procedures to demonstrate histological evidence of caseating granulomas or microbiological evidence of the organism on smear or culture. Drug resistance is an emerging problem that requires vigilance and extra effort to acquire a complete drug sensitivity profile for each tuberculous effusion treated. Nucleic acid amplification tests such as Xpert MTB/RIF can be invaluable in this instance; however, the yield is low in pleural fluid. Treatment consists of standard anti-tuberculous therapy or a guideline-based individualized regimen in the case of drug resistance. There is low-quality evidence that suggests possible benefit from corticosteroids; however, they are not currently recommended due to concomitant increased risk of adverse effects. Small studies report some short- and long-term benefit from interventions such as therapeutic thoracentesis, intrapleural fibrinolytics and surgery but many questions remain to be answered.
Topics: Adenosine Deaminase; Antitubercular Agents; Body Fluids; Drug Resistance, Bacterial; Humans; Interferon-gamma; Pleural Effusion; Thoracentesis; Tuberculosis, Pleural
PubMed: 31418985
DOI: 10.1111/resp.13673 -
Life (Basel, Switzerland) Jan 2023Pleural space infections have been a well-recognized clinical syndrome for over 4000 years and continue to cause significant morbidity and mortality worldwide. However,... (Review)
Review
Pleural space infections have been a well-recognized clinical syndrome for over 4000 years and continue to cause significant morbidity and mortality worldwide. However, our collective understanding of the causative pathophysiology has greatly expanded over the last few decades, as have our treatment options. The aim of this paper is to review recent updates in our understanding of this troublesome disease and to provide updates on established and emerging treatment modalities for patients suffering from pleural space infections. With that, we present a review and discussion synthesizing the recent pertinent literature surrounding the history, epidemiology, pathophysiology, diagnosis, and management of these challenging infections.
PubMed: 36836732
DOI: 10.3390/life13020376 -
Respiratory Medicine Jan 2022Pleural effusion is a frequent complication of acute pulmonary infection and can affect its morbidity and mortality. The possible evolution of a parapneumonic pleural... (Review)
Review
Pleural effusion is a frequent complication of acute pulmonary infection and can affect its morbidity and mortality. The possible evolution of a parapneumonic pleural effusion includes 3 stages: exudative (simple accumulation of pleural fluid), fibropurulent (bacterial invasion of the pleural cavity), and organized stage (scar tissue formation). Such a progression is favored by inadequate treatment or imbalance between microbial virulence and immune defenses. Biochemical features of a fibrinopurulent collection include a low pH (<7.20), low glucose level (<60 mg/dl), and high lactate dehydrogenase (LDH). A parapneumonic effusion in the fibropurulent stage is usually defined "complicated" since antibiotic therapy alone is not enough for its resolution and an invasive procedure (pleural drainage or surgery) is required. Chest ultrasound is one of the most useful imaging tests to assess the presence of a complicated pleural effusion. Simple parapneumonic effusions are usually anechoic, whereas complicated effusions often have a complex appearance (non-anechoic, loculated, or septated). When simple chest tube placement fails and/or patients are not suitable for more invasive techniques (i.e. surgery), intra-pleural instillation of fibrinolytic/enzymatic therapy (IPET) might represent a valuable treatment option to obtain the lysis of fibrin septa. IPET can be used as either initial or subsequent therapy. Further studies are ongoing or are required to help fill some gaps on the optimal management of parapneumonic pleural effusion. These include the duration of antibiotic therapy, the risk/benefit ratio of medical thoracoscopy and surgery, and new intrapleural treatments such as antibiotic-eluting chest tubes and pleural irrigation with antiseptic agents.
Topics: Chest Tubes; Drainage; Exudates and Transudates; Fibrinolytic Agents; Humans; Pleura; Pleural Effusion
PubMed: 34896966
DOI: 10.1016/j.rmed.2021.106706 -
Breathe (Sheffield, England) Dec 2023Pleural tuberculosis (TB) is a common entity with similar epidemiological characteristics to pulmonary TB. It represents a spectrum of disease that can variably... (Review)
Review
UNLABELLED
Pleural tuberculosis (TB) is a common entity with similar epidemiological characteristics to pulmonary TB. It represents a spectrum of disease that can variably self-resolve or progress to TB empyema with severe sequelae such as chronic fibrothorax or empyema necessitans. Coexistence of and progression to pulmonary TB is high. Diagnosis is challenging, as pleural TB is paucibacillary in most cases, but every effort should be made to obtain microbiological diagnosis, especially where drug resistance is suspected. Much attention has been focussed on adjunctive investigations to support diagnosis, but clinicians must be aware that apparent diagnostic accuracy is affected both by the underlying TB prevalence in the population, and by the diagnostic standard against which the specified investigation is being evaluated. Pharmacological treatment of pleural TB is similar to that of pulmonary TB, but penetration of the pleural space may be suboptimal in complicated effusions. Evidence for routine drainage is limited, but evacuation of the pleural space is indicated in complicated disease.
EDUCATIONAL AIMS
To demonstrate that pleural TB incorporates a wide spectrum of disease, ranging from self-resolving lymphocytic effusions to severe TB empyema with serious sequelae.To emphasise the high coexistence of pulmonary TB with pleural TB, and the importance of obtaining sputum for culture (induced if necessary) in all cases.To explore the significant diagnostic challenges posed by pleural TB, and consequently the frequent lack of information about drug sensitivity prior to initiating treatment.To highlight the influence of underlying TB prevalence in the population on the diagnostic accuracy of adjunctive investigations for the diagnosis of pleural TB.To discuss concerns around penetration of anti-TB medications into the pleural space and how this can influence decisions around treatment duration in practice.
PubMed: 38125799
DOI: 10.1183/20734735.0143-2023 -
JAMA Pediatrics Apr 2020Clinical guidelines recommend that children with pleural empyema be treated with chest tube insertion and intrapleural fibrinolytics. The addition of dornase alfa... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of Intrapleural Tissue Plasminogen Activator and Dornase Alfa vs Tissue Plasminogen Activator Alone in Children with Pleural Empyema: A Randomized Clinical Trial.
IMPORTANCE
Clinical guidelines recommend that children with pleural empyema be treated with chest tube insertion and intrapleural fibrinolytics. The addition of dornase alfa (DNase) has been reported to improve outcomes in adults but remains unproven in children.
OBJECTIVE
To determine if intrapleural tissue plasminogen activator (tPA) and DNase is more effective than tPA and placebo at reducing hospital length of stay in children with pleural empyema.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, parallel-group, placebo-controlled, superiority randomized clinical trial included children diagnosed as having pleural empyema requiring drainage aged 6 months to 18 years treated at 6 tertiary Canadian children's hospitals. A total of 379 children were assessed for eligibility; 281 were excluded and 98 were randomized. One child was excluded after randomization for not meeting the inclusion criteria. Data were collected from March 4, 2013, to December 13, 2017.
INTERVENTIONS
Participants underwent chest tube insertion and 3 daily administrations of intrapleural tPA, 4 mg, followed by DNase, 5 mg (intervention group), or 5 mL of normal saline (placebo; control group). Participants, families, clinical staff, and members of the study team were blinded to allocation.
MAIN OUTCOMES AND MEASURES
The primary outcome was hospital length of stay from chest tube insertion to discharge. Secondary outcomes included time to meeting discharge criteria, time to chest tube removal, mean fever duration, additional pleural drainage procedures, hospital readmissions, and total health care cost.
RESULTS
Of the 97 analyzed children with pleural empyema, 52 (54%) were male, and the mean (SD) age was 5.1 (3.6) years. A total of 49 children were randomized to tPA and DNase and 48 were randomized to tPA and placebo. Treatment with tPA and DNase was not associated with decreased hospital length of stay compared with tPA and placebo (mean [SD] length of stay, 9.0 [4.9] vs 9.1 [5.3] days; mean difference, -0.1 days; 95% CI, -2.0 to 2.1; P = .96). Similarly, no significant differences were observed for any of the secondary outcomes. Of the 14 adverse events in the tPA and DNase group, 6 (43%) were serious; of the 21 adverse events in the tPA and placebo group, 8 (38%) were serious. There were no deaths.
CONCLUSIONS AND RELEVANCE
The addition of DNase to intrapleural tPA for children with pleural empyema had no effect on hospital length of stay or other outcomes compared with tPA with placebo. Clinical practice guidelines should continue to support the use of chest tube insertion and intrapleural fibrinolytics alone as first-line treatment for pediatric empyema.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01717742.
Topics: Adolescent; Chest Tubes; Child; Child, Preschool; Deoxyribonuclease I; Empyema, Pleural; Female; Fibrinolytic Agents; Health Care Costs; Humans; Infant; Length of Stay; Male; Patient Readmission; Recombinant Proteins; Tissue Plasminogen Activator
PubMed: 32011642
DOI: 10.1001/jamapediatrics.2019.5863 -
Turk Gogus Kalp Damar Cerrahisi Dergisi Jan 2024Empyema is the infection of the fluid in the pleural space due to different causes. The most common cause of empyema in children is parapneumonic effusion. Although its... (Review)
Review
Empyema is the infection of the fluid in the pleural space due to different causes. The most common cause of empyema in children is parapneumonic effusion. Although its frequency has decreased significantly with the use of antibiotics, it is still a significant cause of morbidity and mortality worldwide. The main aim in the treatment of empyema is to drain the pleural cavity to provide reexpansion of the compressed lung, to treat the parenchymal infection with appropriate antibiotic therapy, and to prevent complications that may develop in the acute and chronic periods. Treatment options for this disease vary depending on the stage of the disease. Treatment success in childhood empyema detected at an early stage is high. The diagnosis and treatment of empyema in children differs from adults. Due to rapid tissue regeneration in childhood, healing can occur without the need for aggressive treatment options.
PubMed: 38584781
DOI: 10.5606/tgkdc.dergisi.2024.25759 -
American Journal of Respiratory and... Dec 2023Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized... (Randomized Controlled Trial)
Randomized Controlled Trial
Early Video-assisted Thoracoscopic Surgery or Intrapleural Enzyme Therapy in Pleural Infection: A Feasibility Randomized Controlled Trial. The Third Multicenter Intrapleural Sepsis Trial-MIST-3.
Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively ( = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) ( = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) ( = 0.023). One serious adverse event was reported in the VATS arm. This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).
Topics: Humans; Thoracic Surgery, Video-Assisted; Feasibility Studies; Communicable Diseases; Pleural Diseases; Sepsis; Enzyme Therapy
PubMed: 37820359
DOI: 10.1164/rccm.202305-0854OC -
The Cochrane Database of Systematic... Oct 2019Pleural infection, including parapneumonic effusions and thoracic empyema, may complicate lower respiratory tract infections. Standard treatment of these collections in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pleural infection, including parapneumonic effusions and thoracic empyema, may complicate lower respiratory tract infections. Standard treatment of these collections in adults involves antibiotic therapy, effective drainage of infected fluid and surgical intervention if conservative management fails. Intrapleural fibrinolytic agents such as streptokinase and alteplase have been hypothesised to improve fluid drainage in complicated parapneumonic effusions and empyema and therefore improve treatment outcomes and prevent the need for thoracic surgical intervention. Intrapleural fibrinolytic agents have been used in combination with DNase, but this is beyond the scope of this review.
OBJECTIVES
To assess the benefits and harms of adding intrapleural fibrinolytic therapy to standard conservative therapy (intercostal catheter drainage and antibiotic therapy) in the treatment of complicated parapneumonic effusions and empyema.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase, ClinicalTrials.gov and the World Health Organization (WHO) trials portal. We contacted trial authors for further information and requested details regarding the possibility of unpublished trials. The most recent search was conducted on 28 August 2019.
SELECTION CRITERIA
Parallel-group randomised controlled trials (RCTs) in adult patients with post-pneumonic empyema or complicated parapneumonic effusions (excluding tuberculous effusions) who had not had prior surgical intervention or trauma comparing an intrapleural fibrinolytic agent (streptokinase, alteplase or urokinase) versus placebo or a comparison of two fibrinolytic agents.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. We contacted study authors for further information. We used odds ratios (OR) for dichotomous data and reported 95% confidence intervals (CIs). We used Cochrane's standard methodological procedures of meta-analysis. We applied the GRADE approach to summarise results and to assess the overall certainty of evidence.
MAIN RESULTS
We included in this review a total of 12 RCTs. Ten studies assessed fibrinolytic agents versus placebo (993 participants); one study compared streptokinase with urokinase (50 participants); and one compared alteplase versus urokinase (99 participants). The primary outcomes were death, requirement for surgical intervention, overall treatment failure and serious adverse effects. All studies were in the inpatient setting. Outcomes were measured at varying time points from hospital discharge to three months. Seven trials were at low or unclear risk of bias and two at high risk of bias due to inadequate randomisation and inappropriate study design respectively. We found no evidence of difference in overall mortality with fibrinolytic versus placebo (OR 1.16, 95% CI 0.71 to 1.91; 8 studies, 867 participants; I² = 0%; moderate certainty of evidence). We found evidence of a reduction in surgical intervention with fibrinolysis in the same studies (OR 0.37, 95% CI 0.21 to 0.68; 8 studies, 897 participants; I² = 51%; low certainty of evidence); and overall treatment failure (OR 0.16, 95% CI 0.05 to 0.58; 7 studies, 769 participants; I² = 88%; very low certainty of evidence, with evidence of significant heterogeneity). We found no clear evidence of an increase in adverse effects with intrapleural fibrinolysis, although this cannot be excluded (OR 1.28, 95% CI 0.36 to 4.57; low certainty of evidence). In a sensitivity analysis, the reduction in referrals for surgery and overall treatment failure with fibrinolysis disappeared when the analysis was confined to studies at low or unclear risk of bias. In a moderate-risk population (baseline 14% risk of death, 20% risk of surgery, 27% risk of treatment failure), intra-pleural fibrinolysis leads to 19 more deaths (36 fewer to 59 more), 115 fewer surgical interventions (150 fewer to 55 fewer) and 214 fewer overall treatment failures (252 fewer to 93 fewer) per 1000 people. A single study of streptokinase versus urokinase found no clear difference between the treatments for requirement for surgery (OR 1.00, 95% CI 0.13 to 7.72; 50 participants; low-certainty evidence). A single study of alteplase versus urokinase showed no clear difference in requirement for surgery (OR alteplase versus urokinase 0.46, 95% CI 0.04 to 5.24) but an increased rate of adverse effects, primarily bleeding, with alteplase (OR 5.61, 95% CI 1.16 to 27.11; 99 participants; low-certainty evidence). This translated into 154 (6 to 499 more) serious adverse events with alteplase compared with urokinase per 1000 people treated.
AUTHORS' CONCLUSIONS
In patients with complicated infective pleural effusion or empyema, intrapleural fibrinolytic therapy was associated with a reduction in the requirement for surgical intervention and overall treatment failure but with no evidence of change in mortality. Discordance between the negative largest trial of this therapy and other studies is of concern, however, as is an absence of significant effect when analysing low risk of bias trials only. The reasons for this difference are uncertain but may include publication bias. Intrapleural fibrinolytics may increase the rate of serious adverse events, but the evidence is insufficient to confirm or exclude this possibility.
Topics: Anti-Bacterial Agents; Drainage; Empyema, Pleural; Fibrinolytic Agents; Humans; Pleural Effusion; Randomized Controlled Trials as Topic; Streptokinase; Thrombolytic Therapy; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator
PubMed: 31684683
DOI: 10.1002/14651858.CD002312.pub4