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BTS GUIDELINES |
1 Consultant in Paediatric Accident and Emergency and General Paediatrics, Chelsea and Westminster Hospital, London, UK
2 Consultant in Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK
3 Chief of Pediatric Cardiothoracic Surgery, Childrens Hospital and Regional Medical Center, Seattle, USA
4 Consultant Microbiologist, Great Ormond Street Hospital for Children, London, UK
5 Consultant Radiologist, Royal Hospital for Sick Children, Bristol, UK
6 Consultant Paediatric Surgeon, Birmingham Childrens Hospital, Birmingham, UK
7 Consultant in Paediatric Respiratory Medicine, Freeman Hospital, Newcastle upon Tyne, UK
8 Consultant in Paediatric Respiratory Medicine, John Radcliffe Hospital, Oxford, UK
9 Specialist Registrar, North Thames Paediatric Respiratory Medicine Training Scheme, UK
Correspondence to:
Correspondence to:
Dr I Balfour-Lynn
Consultant in Paediatric Respiratory Medicine, Royal Brompton Hospital, Syndey St, SW3 6NP London, UK; i.balfourlynn{at}ic.ac.uk
Keywords: guidelines; pleural infection; children; British Thoracic Society
"It seems probable that this study covers the period of practical extinction of empyema as an important disease." Lionakis B et al, J Pediatr 1958.
| 1. SEARCH METHODOLOGY |
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Each section of the guideline was researched and drafted by a subgroup of the Paediatric Pleural Diseases Subcommittee (itself a subcommittee of the BTS Standards of Care Committee). Publications were rated according to the SIGN criteria for the calibre of the methodology of the research to give levels of evidence (table 2
). Tables of evidence were then produced before writing the guideline sections using the SIGN grades of recommendations (table 1
). Once all parts were merged into one document, the whole group then met to discuss the first draft before redrafting took place. This draft was based, where possible, on the published evidence but this was then combined with clinical expertise as required. The resulting draft is therefore a blend of published evidence and clinical experience. This was sent to a group of specialist reviewers listed in the Acknowledgements.
The manuscript was then amended in the light of their comments and the document was reviewed by the BTS Standards of Care Committee following which a further drafting took place. The Quality of Practice Committee of the Royal College of Paediatrics and Child Health also reviewed this draft. After final approval from this Committee, the guidelines were submitted for blind peer review and publication.
1.3 Conflict of interest
All the members of the Guideline Committee submitted a written record of possible conflicts of interest to the Standards of Care Committee of the BTS. There were none. These are available for inspection on request from the Chairman of this Committee.
1.4 Acknowledgements
Funding for literature searches, photocopying and travel to the guideline meeting was kindly provided by the British Thoracic Society. The authors thank the library staff at the National Heart Lung Institute and John Vandridge-Ames at the Royal College of Radiologists for additional searches, Dr Juliet Hale (Consultant Paediatric Oncologist, Royal Victoria Hospital, Newcastle upon Tyne) for advice on malignant effusions, Dr Elizabeth Haxby (Consultant Anaesthetist and Lead Clinician for Clinical Risk, Royal Brompton Hospital, London) for advice on anaesthesia and sedation, Dr Jon Smith (Consultant in Paediatric Cardiothoracic Anaesthesia and Intensive Care, Freeman Hospital, Newcastle upon Tyne) for advice on analgesia, Dr Ravi Jayaram (Specialist Registrar, Royal Brompton Hospital, London) for advice on Appendix 3, and Jayne Wellington for the mountain of photocopying.
The following acted as specialist reviewers: Dr Robert Dinwiddie (Consultant in Paediatric Respiratory Medicine, Great Ormond Street Hospital for Children, London), Dr Iolo Doull (Consultant in Paediatric Respiratory Medicine, University Hospital of Wales, Cardiff), Mr Peter Goldstraw (Consultant Thoracic Surgeon, Royal Brompton Hospital, London), Dr Robert Primhak (Senior Lecturer and Honorary Consultant in Paediatric Respiratory Medicine, Sheffield Childrens Hospital), Dr Paul Seddon (Consultant Paediatrician with an interest in Respiratory Medicine, Royal Alexandra Hospital for Sick Children, Brighton).
The authors also thank the Quality of Practice Committee of the Royal College of Paediatrics and Child Health for reviewing the guidelines and particularly for their comments on methodology.
| 2. INTRODUCTION |
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This guideline has assessed available evidence and attempted to gauge consensus opinion where evidence is unavailable. The lack of paediatric data, in particular from randomised controlled trials, is reflected in the grading of levels of evidence and recommendations in this document. Although there are many grade D recommendations, some of these are safe current practice based on common sense but, since they have never been subjected to a randomised controlled trial, they remain a grade D. An example would be the recommendation to send pleural fluid for bacterial culture. Clearly a D label should not necessarily undermine the significance of the recommendation. For some issues, evidence from adult practice has been assessed and referred to if it seemed applicable to children. It is hoped that these guidelines will facilitate dissemination of evidence, standardisation of patient care, and reduce the morbidity in these patients.
2.2 Epidemiology
Parapneumonic effusion and empyema have an incidence of 3.3 per 100 000 children.4 It has been suggested that the incidence of childhood empyema increased in the UK in the mid to late 1990s,2,3 although this is not a universal finding.8 It is not clear whether this is related to different referral patterns, changes of antibiotic usage in primary care, or whether it was a genuine increase in disease incidence. Parapneumonic effusions and empyema are more common in boys than girls and are more frequently encountered in infants and young children.9 They are also more common in winter and spring,9 presumably due to their infective origin.
2.3 Definition and staging
The definitions of parapneumonic effusion (pleural fluid collection in association with underlying pneumonia) and empyema (the presence of pus in the pleural space) are best considered by reviewing the staging of pleural fluid associated with infection. Pleural infection is a continuum but classically it has been divided into three stages:10
Further complications are uncommon in children but may include bronchopleural fistula, lung abscess, or even perforation through the chest wall (empyema necessitatis).
| Abstracted bullet points Clinical picture
Diagnostic imaging
Diagnostic microbiology
Diagnostic analysis of pleural fluid
Diagnostic bronchoscopy
Referral to tertiary centre
Conservative management (antibiotics ± simple drainage)
Repeated thoracocentesis
Antibiotics
Chest drains
Intrapleural fibrinolytics
Surgery
Other management
Follow up
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2.4 Pathophysiology
The pleural space normally contains 0.3 ml/kg body weight of pleural fluid.12 There is a continuous circulation of this fluid and the lymphatic vessels can cope with several hundred millilitres of extra fluid per 24 hours.13 However, an imbalance between pleural fluid formation and drainage will result in a pleural effusion. In health, pleural fluid contains a small number of cells (mainly mesothelial cells, macrophages, lymphocytes) with a low protein concentration (0.1 g/l), as well as large molecular weight proteins such as lactate dehydrogenase (LDH). Compared with the serum, the pleural fluid has higher levels of bicarbonate, lower levels of sodium, and similar levels of glucose.6
These parameters are altered when disease processes such as infection affect the adjacent lung or vascular tissue and activate an immune response and pleural inflammation. Increased vascular permeability allows migration of inflammatory cells (neutrophils, lymphocytes, and eosinophils) into the pleural space. The process is mediated by a number of cytokinessuch as interleukin (IL)-1, IL-6, IL-8, tumour necrosis factor (TNF)-
, and platelet activating factorreleased by mesothelial cells lining the pleural space.12 The result is the exudative stage of a pleural effusion. This progresses to the fibropurulent stage due to increased fluid accumulation and bacterial invasion across the damaged epithelium.6 Neutrophil migration occurs as well as activation of the coagulation cascade leading to procoagulant activity and decreased fibrinolysis.14 Deposition of fibrin in the pleural space then leads to septation or loculation. The pleural fluid pH and glucose level falls while LDH levels increase.15
2.5 Aetiology
In a previously well child, pleural effusions are usually secondary to acute bacterial pneumonia9 and less often due to chronic infections such as pulmonary tuberculosis.16 When associated with infection, effusions are usually unilateral and bilateral empyemas are unusual, except in one large Turkish series of 515 children where 5% were bilateral.17 Bilateral effusions may indicate tuberculosis or a parasitic infection.18 The rate of parapneumonic effusion complicating pneumonia is said to be 1%,19 although it has been suggested that effusions may be found in up to 40% of adult cases admitted to hospital.10 The prevalence of small parapneumonic effusions is difficult to estimate (and often undetected), and they are unlikely to be reported in case series. Other infections such as lung abscess and chronic suppurative conditions such as bronchiectasis may also produce pleural effusion.9 Predisposing causes include immunodeficiencies, aspiration, post-surgery and trauma.
Pleural effusions are not always secondary to infection and may be genuinely sterile. Rarely, an effusion is the presenting sign of an underlying malignancy in a child who was well before the symptoms related to the effusion. Many of the other secondary causes of pleural effusion will be in children with a known underlying condition such as congenital heart disease, renal disease, connective tissue disorders, and trauma which includes post-cardiothoracic surgery. There are several published case series reporting causes of effusions in children but the proportion of non-infective causes is largely dependent on the referral base and case mix in the particular hospital.9,1921
2.6 Microbiology
The epidemiology has altered significantly over the last 70 years with the discovery of new antibiotics that have different spectra of activity for use in pneumonia. The reported rate of identifying an infectious organism from pleural fluid varies markedly, from 8% to 76%.9,19,21 Precise information is unavailable since much of the historical data is unhelpful due to differences in definitions and inclusion/exclusion criteria. This is further hampered by different pleural fluid sampling rates as well as different culture and identification techniques. Furthermore, in present day practice, pleural fluid culture is often sterile because of antibiotics used before obtaining a pleural fluid sample. In the recent multicentre UK study only 17% of cases were culture positive.22 Even using newer molecular techniquesfor example, pneumococcal or broad range 16S polymerase chain reaction (PCR)an aetiological agent was only detected in about 75% of culture negative cases, although this does represent an improvement.23,24
2.6.1 Acute bacterial infection
In the pre-antibiotic era, Streptococcus pneumoniae was the major pathogen recovered from pleural fluid, followed by ß-haemolytic streptococci (probably Streptococcus pyogenes) and Staphylococcus aureus.25,26 With the introduction of sulphonamides and then penicillin, the incidence of S pneumoniae and S pyogenes was markedly reduced and the relative proportion of S aureus increased, especially in the late 1950s as the rate of penicillin resistant S aureus began to increase.25S aureus was particularly evident in the first 6 months of life, and overall accounted for 29%9 to 63%27 of cases. There have also been reports of empyema due to methicillin-resistant S aureus in children.28,29
Following the introduction of penicillinase stable penicillins and other antistaphylococcal agents, the relative proportion of empyema due to S pneumoniae has increased once more. Currently it seems to be emerging as the predominant pathogen in childhood empyema, although this is not always reflected in culture results as many are culture negative.3,3032 Nevertheless, S pneumoniae was the principal organism in three recent case series from the USA,4,29,33 and the majority of culture negative cases in two UK series have been shown to be S pneumoniae by molecular techniques.23,24 In the Newcastle study, evidence of S pneumoniae was found in 75% culture negative pleural fluid samples by PCR methods as well as latex agglutination testing for pneumococcal antigen;24 53% of these were capsular serotype 1 and all were penicillin sensitive.
Other bacteria include S pyogenes,19,34Haemophilus influenzae type b,21Mycoplasma pneumoniae,35,36Pseudomonas aeruginosa,27,37 and other streptococcal species (including viridans streptococci38 and streptococci of Lancefield group F39). Rarer bacterial organisms isolated include Klebsiella,40Enterobacter,37Proteus species,37Salmonella,41 and Yersinia.42 Anaerobic organisms such as Bacteroides species and Peptostreptococcus are rarely isolated in children but may be associated with aspiration pneumonia or foreign bodies,12,43 as may Streptococcus milleri;22 they must always be considered in children with delayed neurodevelopment. Disseminated Fusobacteriumnecrophorum infection (Lemierre syndrome) is a potentially fatal condition which typically follows a severe pharyngitis and may be seen in older children (and young adults); although rare, it seems to be increasing in incidence.44
The bacterial aetiological profile differs in developing countries with S aureus being the predominant pathogen, especially during the hot and humid months when staphylococcal skin infections are more prevalent.17,45 There has been a decline in culture positive S pneumoniae, probably because of prior antibiotic use.45 Various Gram negative organismsfor example, Enterobacteriaceae such as Klebsiella spp and Pseudomonas aeruginosaare also more common than in the UK; they are not limited to infants and may be associated with protein energy malnutrition.27,37,45,46
2.6.2 Mycoplasma, Legionella and viruses
Pleural effusion is reported in association with mycoplasma infection although empyema is rare.47 Mycoplasma serology, when performed, suggests involvement in some cases30,36 but most series do not report serology results and paired samples may not have been taken. Legionella pneumophila48 and primary viral pneumonia49 may also be associated with pleural effusion but the contribution of these agents to pleural empyema is not accurately known as few studies report adequate investigations of all cases. Besides, a viral infection may simply precede a secondary bacterial infection which then causes the empyema. Certainly adenovirus36,49 and influenza virus35 can cause effusions, but they are rarely large.
2.6.3 Mycobacterial infection
Tuberculous empyema can result from progressive pulmonary tuberculosis. It has been reported to account for up to 6% of all empyema cases worldwide,6 but with aggressive modern antituberculous chemotherapy it is seldom seen in the UK.12
2.6.4 Other organisms
Fungal causes are usually nosocomial in origin50,51 or, in the case of the rare Histoplasma infection, follow exposure.52,53 Finally, there is a single case report of Entamoeba histolytica.54
2.7 Clinical picture
There are two common patterns of presentation. In the first, the child has classic symptoms of pneumoniafor example, fever, cough, breathlessness, exercise intolerance, poor appetite, abdominal pain, fetor oris (halitosis), lethargy and malaise.55 However, in the presence of an effusion they are often more unwell than with simple pneumonia alone. They may have pleuritic chest pain and may lie on the affected side to splint the involved hemithorax and provide temporary analgesia.12 On examination a pleural effusion is suggested by unilateral signs of decreased chest expansion, dullness to percussion, reduced or absent breath sounds, and scoliosis. There may also be cyanosis due to ventilation-perfusion mismatch. The effusion is often obvious on the initial chest radiograph. All children with parapneumonic effusion or empyema should be admitted to hospital.
The second scenario is of the child who has been diagnosed with pneumonia but does not respond to the usual and appropriate treatment. We would reiterate the recommendations from BTS guidelines for the management of community acquired pneumonia in childhood55 that, if a child remains pyrexial or unwell 48 hours after admission with pneumonia, re-evaluation is necessary with consideration given to possible complications. Careful clinical examination and a repeat chest radiograph are warranted.
2.8 Outcome and prognosis
The prognosis in children with empyema is usually very good. Follow up studies have shown that, despite the heterogeneity of treatment approaches, the majority of children make a complete recovery and their lung function returns to normal.5663 Other studies have shown minor abnormalities in lung function of both a restrictive64,65 and obstructive nature,61 but the children were still asymptomatic with normal exercise tolerance.61,64,65 The chest radiograph returns to normal in the majority of children (6083%) by 3 months, in over 90% by 6 months, and in all by 18 months.30,62
| 3. DIAGNOSIS |
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3.2 Physical examination
A pleural effusion is suggested by unilateral signs of decreased chest expansion, dullness to percussion, and reduced or absent breath sounds. The assessment of severity is the same as that for any childhood pneumonia (table 3
), but measurement of oxygen saturation (SpaO2) is particularly important with levels below 92% indicating severe disease.55 Examination should also include assessment of the childs state of hydration, their height and weight, the presence of a scoliosis, and any underlying disorders.
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Box 1 Initial investigations for suspected parapneumonic effusion
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3.4 Imaging
3.4.1 Chest radiograph
Obliteration of the costophrenic angle is the earliest sign of a pleural effusion, and a rim of fluid may be seen ascending the lateral chest wall (meniscus sign) on a posteroanterior or anteroposterior radiograph. If the film is taken when a (younger) child is supine, the appearance can be of a homogeneous increase in opacity over the whole lung field without blunting of the costophrenic angle or a classic pleural based shadow.66 When there is a "white out" it is not always possible to differentiate solid underlying severe lung collapse/consolidation from a large effusion. Radiographs alone cannot differentiate an empyema from a parapneumonic effusion.66 A lateral chest radiograph rarely adds anything extra, although can sometimes be helpful in differentiating pleural from intrapulmonary shadowsfor example, air in the intrapleural space v an intrapulmonary abscess cavity. Finally, any scoliosis can be detected on a plain chest radiograph.
3.4.2 Ultrasound scan of chest
Chest ultrasonography can detect the presence of fluid in the pleural space, so is particularly useful when there is a "white out" on the chest radiograph.6 Although ultrasound cannot reliably establish the stage of pleural infection,11 it can estimate the size of the effusion, differentiate free from loculated pleural fluid, and determine the echogenicity of the fluid.66 Ultrasound may also demonstrate pleural thickening and assist in the diagnosis of effusion secondary to tuberculosis (for example, the presence of diffuse small nodules on the pleural surface).67 Finally, it can be used to guide chest drain insertion or thoracocentesis with the radiologist or radiographer marking the optimum site for drainage on the skin.6871 Ultrasound can conveniently be carried out at the bedside with modern portable units.
3.4.3 Is a CT scan necessary in addition to ultrasound?
Radiation from a CT chest scan can be high (depending on several factors including the machine, scanning technique, and size of the child), ranging from up to 400 chest radiograph equivalents to as few as 20. There has been little research on the use of ultrasound and CT scanning in paediatric empyema. However, as discussed in section 3.4.2, ultrasound can confirm the presence of pleural fluid (differentiating it from pulmonary infiltrates) so is critical in the diagnosis of parapneumonic effusion/empyema. Although ultrasound cannot usually identify the stage of the pleural effusion,11 a study of 320 adults and some children showed that it might sometimes help to distinguish exudative pleural effusions from transudates.72 The exudates appeared as complex effusions or homogeneously echogenic effusions on ultrasound and these were due either to empyema or haemorrhage. Fibrinous septations are better visualised using ultrasound than CT scans. Ultrasound has also been shown to be good at distinguishing fluid from solid material in the pleural space.73 It will not predict those patients who will fail with chest drain and fibrinolytics alone and subsequently require surgery.11 Ultrasound scanning is now readily available and is the preferred investigation in children, especially as no sedation is necessary and it involves no radiation. It enables the exact location of any fluid collection to be determined and allows guided diagnostic aspiration if required.70,71 Ultrasound is sufficient in the majority of paediatric cases.
In a study of 30 children CT scanning was not helpful in differentiating empyema from parapneumonic effusion.74 Furthermore, in a review of ultrasound and CT scanning in a group of 50 adults with parapneumonic effusion requiring drainage, neither technique reliably identified the stage of the pleural effusion, although pleural thickness on the CT scan was greater in those with frankly purulent effusions.11 CT scanning of the chest with contrast enhancement assists in delineating loculated pleural fluid and can also detect airway or parenchymal lung abnormalities such as endobronchial obstruction or a lung abscess, as well as helping with mediastinal pathology.75,76 While unnecessary for most cases of paediatric empyema, it has a role in complicated cases (including initial failure to aspirate pleural fluid and failing medical management) and particularly in immunocompromised children where a CT scan could reveal other serious clinical problems. Many surgeons will require a CT scan before surgery (either open thoracotomy or thoracoscopy) to delineate the anatomy further and to check for an intrapulmonary abscess.
3.5 Blood tests
Are blood tests helpful in the investigation or management of parapneumonic effusions/empyema?
3.5.1 Blood cultures
In the BTS guidelines for community acquired pneumonia (CAP) in children it is recommended that blood cultures should be performed in all children suspected of having bacterial pneumonia.55 A recent large retrospective case series of 540 children in the USA with CAP, 153 of whom went on to develop an empyema, confirms that this is worthwhile.5 Blood cultures were positive in 15/153 (10%) with empyema and 25/387 (6.4%) of those with pneumonia alone. Another recent series in 76 children with complicated parapneumonic effusions found positive blood cultures in 22% compared with pleural fluid which was positive in 33% of cases.29 In another series, blood culture was positive in 10/56 cases (18%) of empyema in children, all with S pneumoniae, and in 7/10 positive blood cultures the pleural fluid was sterile.4
3.5.2 Acute phase reactants
Significant parapneumonic effusions/empyema are uncommon in viral infections. Acute phase reactants such as white cell count, total neutrophil count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin have been generally performed in the belief that they help distinguish bacterial from viral infections. However, a number of prospective studies have examined the usefulness of acute reactants in distinguishing bacterial from viral pneumonia and showed them to be unhelpful.7781 For example, Nohynek et al77 showed that the distribution of ESR, full blood count, and CRP values in children hospitalised for acute lower respiratory infection (n = 121) was wide, and they could not identify cut off points that would reliably distinguish bacterial from viral infections. Virkki et al81 studied 254 children with CAP and showed that the proportion with raised white cell count or ESR did not differ between bacterial or viral pneumonias, and that high CRP levelsalthough significantly more common in bacterial pneumoniawere too insensitive to be useful clinically.
No studies were found which examined the specific relationship between acute phase reactants and the development of a parapneumonic effusion/empyema. However, given the above, it is unlikely that they could be discriminatory. In addition, no studies were found which examined trends in acute phase reactants with clinical progress, but clinical practice has shown that serial measurements of CRP and the white cell count can be helpful.
3.5.3 Serum albumin
This is often low but albumin replacement is rarely necessary.
3.6 Microbiology (non-pleural fluid)
If the child is expectorating sputum (which is rare), it should be sent for bacterial culture as it is likely to represent the infecting organism from the lower airways. Bacteria cultured from the nasopharynx or throat may not necessarily be in the lower airways; however, if the child has a general anaesthetic, tracheal aspiration can be performed for bacterial culture. The importance of blood cultures has been discussed in section 3.5. The detection of an immune response may indicate the infecting organismfor example, mycoplasma serology, antistreptolysin O or viral titres.19,22,30 However, the need for paired serum samples often makes this irrelevant as the child will usually have recovered and been discharged, making a second venepuncture irrelevant. Additional tests may be performed but there are few data on sensitivityfor example, the detection of S pneumoniae antigen in serum. In the future, additional causative agents may be detected from circulating microbial DNA. Mantoux testing and sputum for acid-fast bacilli should be performed if risk factors for tuberculosis are presentfor example, recent travel to area of high prevalence, close contact with sputum positive tuberculosis, high risk ethnic population.
3.7 Pleural fluid
If there is any indication the effusion is not secondary to infection, consider a small volume diagnostic tap for cytological analysis before chest drain insertion, avoiding general anaesthesia/sedation (section 3.7.2).
3.7.1 Microbiology
The issue of causative organisms has been addressed in section 2.6. Although pleural fluid is often sterile due to prior administration of antibiotics,22 it must be sent for culture. However, additional simple or specialist alternative non-culture techniques are available which may improve the yield. These include:
3.7.2 Cytology
Whenever pleural fluid has been aspirated a sample should be sent for a differential cell count and Gram stain. A classic result of Gram positive cocci with 90% polymorphonuclear leucocytes on Gram stain differential is enough to make full cytological analysis unnecessary. If infection is not immediately apparent, a sample should be sent for cytological analysis to whichever laboratory performs a cytospin (rather than simply relying on the Gram stain differential from the microbiology laboratory). Parapneumonic pleural effusions are dominated by polymorphonuclear leucocytes but a predominance of lymphocytes in an exudate should raise the possibility of tuberculosis or malignancy.82 Staining and culture for acid-fast bacilli should be performed on pleural fluid samples anyway, but a Mantoux test should be considered when lymphocytes predominate, particularly if the history is suggestive of tuberculosis. As many as 10% of tuberculous pleural effusions, however, are predominantly neutrophilic.84
Most malignant effusions in children will be blood stained but, as in adults, cytological examination may not reveal malignant cells.82 A CT chest scan should be considered when malignancyfor example, lymphomaneeds to be excluded. Obtaining pleural fluid solely for the purposes of cytological analysis is rarely necessary in children. However, diagnostic aspiration of fluid should be performed if there are any atypical features to suggest the presence of malignancy, such as the absence of acute fever or pneumonia, or evidence of an underlying mediastinal mass or lymphadenopathy. Large volume aspiration and general anaesthesia pose a significant risk of sudden death in children with superior mediastinal obstruction related to malignancy.85 Aspiration of pleural fluid should therefore be of small volume (e.g. 5 ml) for diagnostic purposes only and general anaesthesia/sedation avoided under such circumstances. Since most paediatric malignancies are haematological, specimens should be sent to the haematology laboratory for cytospin and then forwarded to the cytology laboratory if other malignant cells are identified.
3.7.3 Biochemistry
In adult practice, biochemical analysis of pleural fluid plays an important part in the management of pleural effusions. Protein levels or Lights criteria differentiate exudates from transudates,82 while infection is indicated by pleural acidosis associated with raised LDH and low glucose levels.6 In terms of treatment, the pH may even guide the need for tube drainage, suggested by pH <7.2 in an infected effusion,82 although the absolute protein values are of no value in determining the likelihood of spontaneous resolution or chest drain requirements.6
There are no data to suggest that the biochemical characteristics of pleural fluid in children are any different from adults. However, biochemical analysis has not been shown to be of any value in the practical management of children with pleural effusions, but equally nor has it been shown to be of no value. This probably reflects the fact that the vast majority of these effusions are parapneumonic and most respiratory paediatricians in the UK do not use biochemical indices to plan management of an empyema. Certainly, routine aspiration of pleural fluid is not normally performed solely for the purpose of biochemical analysis.
3.8 Bronchoscopy
The role of bronchoscopy in empyema management has not been formally studied6 but there is no indication for routine flexible bronchoscopy in children. Although bronchoalveolar lavage may diagnose the infecting organism, this is unnecessary when pleural fluid is available. The possibility of foreign body aspiration must be considered in younger children and would be an indication for bronchoscopy.
| 4. TREATMENT |
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4.2 Referral to tertiary centre
If there is no facility to perform chest ultrasound and confirm diagnosis, refer immediately.
Once diagnosed by chest radiography and ultrasound, contact tertiary centre to discuss a management plan. It is not always necessary to transfer the child immediately, but it is worthwhile liaising with an experienced unit over further management.
Occasionally the child can stay in the secondary centre for conservative management, particularly if the effusion is small or the child is not unwell and has no oxygen requirement (section 4.3).
Our recommendation is that children who require chest tube drainage are transferred to a tertiary paediatric respiratory unit. However, some secondary centres are able to insert a chest drain, in which case treatment may be initiated without early transfer, but recent experience shows that many anaesthetists are unwilling to administer a general anaesthetic to a child with a pleural effusion and prefer the child to be transferred to an experienced centre. Furthermore, management of chest drains is best carried out on a ward with sufficient experience (section 4.5.17).
If there is a large effusion or the child is unwell (with respiratory distress and an oxygen requirement), it is recommended that the child is transferred immediately for further management. While this should be done promptly, transfer is rarely an emergency. In adult practice there is evidence that delay in chest tube drainage is associated with increased morbidity, hospital stay, and even mortality.6 Although such evidence is lacking in children, and accepting that their prognosis is generally much better than adults, it is still the case that management is harder in those with an advanced organised empyema, so prompt recognition and treatment remains important.
Refer to a paediatric respiratory unit rather than directly to paediatric or thoracic surgeons.
4.3 Conservative management (antibiotics ± simple drainage)
4.3.1 What proportion respond to conservative management and what is the "cost" in terms of duration of treatment and hospital stay?
Conservative management of pleural infection consists of antibiotic treatment alone or antibiotics plus simple drainage. Many small parapneumonic effusions will respond to antibiotics without the need for further intervention. However, effusions which are enlarging and/or compromising respiratory function in a pyrexial unwell child need drainage. Studies on conservative management are retrospective case series and many are historical. Since the mid 1990s, management strategies using fibrinolytics and early thoracoscopic surgery have evolved but six studies (three from Turkey) of conservative management in children have been published in the past 10 years.30,46,62,63,86,87 These studies suggest that, overall, 6080% of cases will respond to conservative medical management but hospital admission may be long.
Gocmen et al62 reported the successful treatment of 66 of 72 children (92%) with antibiotics and simple tube drainage between 1985 and 1990. Drainage was for a mean of 6 days (range 215) and hospital stay was a mean of 9 days (range 535). Three children failed treatment and went for surgery at a mean of 38 days after admission. Long term outcome was excellent with complete radiological clearance by 6 months and normal long term lung function. Less good results were reported by Tiryaki et al46 who treated 160 children between 1988 and 1994. Two were treated successfully with antibiotics alone, 17 had primary surgery, and 141 were treated initially with simple tube drainage. Of these, 30 had persistent symptoms at 10 days and went to surgery. Overall therefore in this series conservative treatment was successful in 70%. The duration of hospital stay was not reported. The third Turkish study86 was of 49 patients of whom only two went to surgery but the mean (SD) hospital stay was 28 (10.2) days. Chan et al87 reported on 47 cases over 26 years from Canada. Eight children had antibiotics alone (mean hospital stay 27 days), 32 children had additional tube drainage (mean hospital stay 23 days), and seven had surgery (hospital stay 40 days); these are much longer than would be expected currently in the UK. One UK study reported 54 children treated between 1989 and 1997.30 Forty seven patients had closed tube drainage for a median of 8 days (range 329) and 21 patients had surgery for persistent symptoms at a median of 10 days from admission. Overall, 33 patients (61%) responded to medical management and had a mean (SD) hospital stay of 13.4 (5.3) days, which was significantly less than the 18.6 (9.7) days for those needing surgery. The overall median hospital stay for the group was 14.5 days. Long term outcome was good with normal radiological appearances at 6 months. Finally, in a recent small case series from a secondary paediatric UK centre, 14 children were treated with antibiotics and tube drainage alone.63 Although none required surgery and lung function measured 324 months later in 13/14 children was excellent, the hospital stay was rather prolonged (median 14 days, range 528).
4.3.2 Is there a role for repeated thoracocentesis?
There has been one study reporting repeated ultrasound guided needle thoracocentesis in children and comparing the outcome with tube drainage.88 The study was not randomised and the two treatments were carried out in separate hospitals. Children with empyema and pleural fluid occupying over one third of lung space on the chest radiograph were eligible. Thirty five children had alternate day repeated needle drainage (16 FG) on a mean of 2.4 (range 14) occasions under local anaesthetic. Five children failed to respond (two had tube drainage plus urokinase and three had surgery). Thirty two children had closed tube drainage as initial treatment and five failed (two then responded to urokinase and three needed surgery). There was no difference between the groups in duration of pyrexia or duration of hospital stay (the latter was prolonged: mean (SD) 22 (7) days).
While simple needle thoracocentesis may be considered in older childrenparticularly when they can cooperate sufficiently to allow the use of local anaesthetic alonerepeated taps are not recommended and a drain should be inserted once it is clear a second tap is required. For those children who require a general anaesthetic for the procedure, it is prudent to insert a proper drain the first time or consider the early surgical approach.
4.4 Antibiotics
4.4.1 Initial "blind" antibiotic treatment
All cases should be treated with intravenous antibiotics. Management of early pneumonic changes should be according to the BTS guidelines on the management of community acquired pneumonia in children.55 Once an effusion has been identified, antibiotic selection should cover the likeliest organisms which have been discussed in section 2.6. This should take into account any predisposing condition and potential pathogen exposure. In particular, it is relevant whether pleural infection arises secondary to a community or hospital acquired pneumonia, whether it is postoperative or following trauma, and whether aspiration is likely to have occurred. Other causes should also be considered including exposure to mycobacterial infection. Broad cover is important in immunocompromised patients.
Adequate doses must be given to ensure pleural penetration although there are limited data in children. Standard doses can be obtained from the Royal College of Paediatrics and Child Health publication "Medicines for Children".89 Work in adults has shown good penetration into infected pleural fluid by several antibiotics including penicillin, carbenacillin, clindamycin and amikacin,90 as well as ciprofloxacin.91 Cefuroxime levels have been shown to be adequate in paediatric infection.92
Empirical treatment must cover S pneumoniae,S pyogenes and S aureus. Most strains of S pneumoniae causing serious infection in the UK are still predominantly susceptible to penicillin, although penicillin resistance is generally increasing.55 Antistaphylococcal cover is mandatory if pneumatoceles are evident. If aspiration is likely (relevant history or delayed neurodevelopment), cover for anaerobes and S milleri must be included and, in older children, cover for Fusobacterium is important. Metronidazole should be considered for older children (mid to late teens) to cover Fusobacterium unless co-amoxiclav or clindamycin are used. Mycoplasma is a rare cause of empyema and a macrolide need not be included.
The potential choice of agents is wide and has only been studied once in a randomised trial, comparing cefuroxime with dicloxacillin/chloramphenicol where equal efficacy was found.92 Recommendations are therefore not evidence based, and initial treatment should be guided by local antibiotic policy/restrictions where consideration must be given to the emergence of resistant organisms. Suitable options are shown below.
(A) Following community acquired pneumonia
Penicillin allergic patients can be treated with clindamycin alone.6 Other broad spectrum agents may be appropriate but are not indicated unless by local antibiotic policyfor example, piperacillin/tazobactam or meropenem.
(B) Hospital acquired pneumonia and following surgery/trauma/aspiration
Broader spectrum agents are indicated to include cover for aerobic Gram negative rods.
(C) Mycobacterium tuberculosis
Mycobacterial treatment should not be started empirically unless there is very strong circumstantial evidence. The BTS guidelines should be used and a tuberculosis specialist should be involved with the care.93
4.4.2 Continuation of antibiotic treatment
If the pleural fluid is culture positive, further antibiotic management should take into account antibiotic sensitivities.6 However, due to the frequency of culture negative cases, the initial blind antibiotic treatment is often continued, especially if clinical improvement is seen. There are no data from randomised trials on an appropriate length of treatment and no data on whether different organisms require different durations. Many UK centres continue with intravenous antibiotics until the child is afebrile or at least until the chest drain is removed. Oral antibiotics such as co-amoxiclav are then given at discharge for 14 weeks, but longer if there is residual disease.
4.5 Drain insertion
4.5.1 Who should insert the drain?
Who inserts the drain will depend largely on the size and type of drain being used. Rigid large bore drains will be inserted by paediatric surgeons or (paediatric trained) thoracic surgeons, and it would be expected that surgeons would insert drains required in the postoperative period following cardiac or thoracic surgery. Pigtail or small bore soft drains (inserted by the Seldinger technique) will be used by respiratory paediatricians or interventional radiologists. It is unlikely that general paediatric trainees will gain enough experience in chest drain insertion. Either way, adequate training and supervision is mandatory as it has been shown that this reduces the risk of complications.94 Whoever inserts the drain, it is vital to have a suitable assistant and trained nurse, particularly when this is done using local anaesthesia.
4.5.2 Pre-drainage check list
There is no published evidence in children or adults that abnormal blood clotting or platelet counts affect bleeding complications of chest drain insertion. However, where possible it is obvious good practice to correct any coagulopathy or platelet defect before drain insertion. Routine pre-procedure checks of platelet count and prothrombin time are only required in those patients with known risk factorsfor example, those on haemodialysis, following cardiac surgery or after chemotherapy.95 This is an uncommon scenario as the majority of children are well before the initiating pneumonia.
4.5.3 What radiological investigations should be performed before drain insertion?
As discussed in sections 3.4.1 and 3.4.2, a chest radiograph is mandatory, as is an ultrasound scan to confirm the diagnosis. The ultrasound can reveal the exact location of the fluid collection and the skin can be marked to indicate the optimum site for drain insertion.70,71,96 The position of the patient must be clearly documented so that it is the same when the aspiration is performed later. It is important though to ensure the "X" is not placed in a position that will make it more uncomfortable for the child to lie on once the drain is in place. If necessary, an interventional radiologist may insert the drain using either ultrasound or, rarely, CT scan guidancefor example, when initial aspiration fails.96101
4.5.4 Informed consent
The doctor carrying out the procedure, or an appropriately trained individual with sufficient knowledge of the procedure to explain its nature and risks, must obtain informed consent according to the General Medical Council guidelines.
4.5.5 Anaesthesia
Should general anaesthesia be used or sedation with local anaesthesia only?
It is difficult to insert a chest drain in most children without general anaesthesia as they need to cooperate and keep very still, although some older children and adolescents can do this. There is controversy and no consensus over the use of conscious sedation for procedures in children and practice varies across the UK. There is also little evidence on which to base guidelines. General anaesthesia is usually considered safer than intravenous sedation in children who have respiratory compromise (especially by anaesthetists), and it is the preferred option for non-cooperative children. Local anaesthetic will still be used in an anaesthetised patient for pain control and a paravertebral block with bupivicaine can be used to provide postoperative pain relief.102,103 Whilst under general anaesthesia, a percutaneously inserted long line can be placed in case the course of antibiotics is prolonged.
The main advantage of using sedation is logistic as it can be done at a convenient time. Safety remains paramount and it should only be carried out by someone trained in the use of conscious sedation, airway management, and resuscitation of children. Furthermore, the same level of monitoring used for general anaesthesia should be employed. It must be carried out in a suitable environment, with an experienced assistant in attendance to monitor the patients vital signs. Intravenous access is mandatory. Local anaesthetic is infiltrated into the skin at the marked site using a small gauge needle to raise a dermal bleb, before deeper infiltration in the intercostal space into the subcutaneous tissue, intercostal muscles, periosteum of the rib, and parietal pleura. Use 0.25% bupivacaine with a maximum dose of 2 mg/kg (0.8 ml/kg) in 8 hours, and in those aged 1218 years the maximum safe dose is 150 mg (60 ml) in 8 hours (such a large dose is unnecessary); or lignocaine (lidocaine) hydrochloride up to 3 mg/kg with a maximum in those aged 1218 years of 200 mg in 4 hours.89
4.5.6 Equipment
In the case of a general anaesthetic, the procedure will take place either in an anaesthetic room or operating theatre. In the case of sedation, it must be carried out in a properly equipped room which must include suitable lighting, a tipping trolley/bed, resuscitation and monitoring equipment, with oxygen and suction available. All the required equipment should be available before starting the procedure (Appendix 2).
4.5.7 Drain insertion site and patient position
Small bore drains will be inserted at the optimum site suggested by the chest ultrasound and marked with an "X".6871 Larger surgically placed drains are best inserted in the mid axillary line through the "safe triangle".95 This is the triangle bordered by the anterior border of latissimus dorsi, the lateral border of the pectoralis major muscle, a line superior to the horizontal level of the nipple, and an apex below the axilla. This position minimises risk to underlying structures and avoids damage to muscle and breast tissue resulting in unsightly scarring. A more posterior position may be chosen if suggested by the presence of a locule but, while this is safe, it is more uncomfortable for the patient to lie on after insertion and there is a greater risk of the drain kinking. In addition, the intercostal arteries run in the middle of the intercostal spaces posteriorly (whereas laterally they run under the ribs), so there is an increased risk of traumatic insertion if drains are placed posteriorly.
Under general anaesthesia the child will be flat on his/her back but, if the "X" is quite posterior, roll the patient to make access easier. The cooperative child who is undergoing local anaesthesia is preferably positioned for drain insertion on the bed, slightly rotated, with the arm on the side of the lesion behind the patients head to expose the axillary area.104 An alternative position may be upright leaning over an adjacent table with a pillow or in the lateral decubitus position.105
4.5.8 Drain size
Large bore drains were used in the past because of concerns that smaller tubes might become blocked by thick pus, and they tend to be preferred by surgeons.106108 Controversy still remains about the optimum drain size and no proper randomised trials have been performed. However, the majority of paediatricians now use smaller catheters (812 FG) and studies have shown (in adults) that these are as effective as larger bore tubes.109 The children are more comfortable and tolerate the procedure better;110 they also seem to move more freely with smaller soft drains which aids recovery. In the UK multicentre study of urokinase, post hoc analysis showed that a shorter hospital stay (geometric mean 7.2 v 9.4 days) was associated with the use of small percutaneous catheters (mean size 10.5 FG) rather than larger surgical drains (mean size 20.1 FG).22 It should be remembered, however, that this may have been due to a centre effect and the trial did not set out to study chest drain size. Ultrasonographically guided insertion of small pigtail catheters for treatment of early loculated empyema has been well studied in children and found to be effective.97
4.5.9 Sterile technique
Sterile technique is essential to avoid wound site infection or secondary empyema. Sterile gloves, gown, equipment and the use of sterile towels after effective skin cleansing