Pleural empyema

Disclaimer These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline.  Read the full PCH Emergency Department disclaimer.

Aim

This guideline provides a clinical framework for the assessment, investigation and management of children and adolescents presenting to PCH with a pleural empyema.

Background  

There is no agreed standard treatment regimen for childhood empyema.

Current literature suggests that there is no significant difference in outcomes between chest drain with intrapleural fibrinolytics or VATS. Chest drain and intrapleural fibrinolytics may offer the same clinical benefit but at a lower cost. The course of treatment depends on several factors including the child’s respiratory function, size and loculation of the fluid collection, as well as the response to initial interventions. Whilst some data suggests a slight reduction in length of stay with Video-Assisted Thoracoscopic Surgery (VATS) compared with chest drain, primary management with small bore catheter and fibrinolysis is sufficient in the vast majority of paediatric patients who require drainage. ^{1, 3-5}

Definitions

Pleural empyema develops most commonly secondary to bacterial pneumonia. 

PPE: Parapneumonic effusion: 

• PPE and empyema represent a continuum from clear fluid with low white cell numbers to overt pus. 
• A simple PPE may progress from the exudative stage with anechoic non-septated fluid (stage 1), through hyperechoic fluid with fibrinous septation (stage 2) to an organisational stage with hyperechoic loculations with or without thick pleural peel (stage 3). ^1,2

VATS: video-assisted thoracoscopic surgery.

Key Points

• Streptococcus pneumoniae is the most common pathogen associated with pleural empyema⁶
• The possibility of PPE should be considered in all children with pneumonia.
• Chest X-ray (CXR) and chest ultrasound are the central radiological investigations 
• Routine CT chest is not indicated, but should be considered if:
  • An infective cause is in doubt 
  • Thoracotomy is being considered
  • There is complex disease 
• Empiric intravenous antibiotics are the first line of treatment (see Acute respiratory tract infection - ChAMP guideline)
• If there is a moderate-large collection seen on ultrasound, chest drain insertion and intrapleural-fibrinolytic installation should be considered in conjunction with antibiotics.
• VATS should be reserved for failure of conservative management.

Aetiology

• Most children and adolescents with empyema are previously healthy²
• The most common pathogens in Australia are Streptococcus pneumoniae and Staphylococcus aureus (both methicillin susceptible S.aureus - MSSA and methicillin resistant S.aureus - MRSA)⁶
• Other organisms include Group A Streptococcus; Streptococcus milleri group, Haemophilus influenzae. 
• Uncommon causes are Mycoplasma pneumonia, Chlamydia pneumonia, Pseudomonas aeruginosa, Burkholderia pseudomallei and Klebsiella species. In children at risk of aspiration, anaerobic organisms should be considered.
• Mycobacterium tuberculosis may present with pleural effusion with or without underlying lung changes.

Management Overview (see quick guide)

Initial investigations

• CXR and chest ultrasound 
• Routine CT chest is not indicated

Initial Treatment^1,2,7,8

• Empiric intravenous antibiotics are the first line of treatment.
• Chest drain insertion and intrapleural-fibrinolytic instillation should be considered as early as possible for moderate and large PPE.
• Small bore chest drain is as effective as a large bore chest drain.⁸

Surgical Treatment

• Surgical interventions include VATS, mini-thoracotomy or open decortication.
• There is some evidence that primary VATS may reduce hospital length of stay in some patients, however any invasive procedure should be reserved for failure of conservative management. ^{3, 5, 9}

Diagnosis

1. History

• Patients usually present with symptoms of pneumonia - cough, shortness of breath, fever, lethargy and chest or abdominal pain. 
• In a patient with pneumonia, empyema should be considered where there is persisting fever or a lack of clinical improvement after 48 hours of antibiotics.

2. Physician examination

• Parapneumonic effusion is typically characterised by reduced chest movement, dullness to percussion and reduced breath sounds.

3. Imaging

Chest X-Ray 

Early signs include blunting of the costophrenic angle and a lateral rim of fluid around the lung. With large effusions there may be a complete ‘white out’ of the lung field making it impossible to differentiate between pleural fluid and consolidated lung; the presence of mediastinal shift away from the pathology supports the diagnosis of a pleural collection and ultrasound can provide non-invasive differentiation.

Chest Ultrasound

Ultrasound is the central investigation in empyema. It is non-invasive, portable, and cheap and does not involve ionising radiation. It can differentiate pleural fluid from consolidated lung, demonstrate fibrinous strands within the fluid, assess loculation of fluid, estimate the size of effusion and guide chest drain placement. 

CT Chest

• Chest CT does not provide benefit over ultrasound for determining the size and nature of parapneumonic effusions. Chest CT does provide information about parenchymal changes of the underlying lung. Chest CT is often useful when a patient’s clinical situation worsens, does not improve as expected, or if surgical intervention (e.g. decortication) is being considered.
• Chest CT is also considered in cases where there is concern that infection is not the cause, particularly in those with late presenting empyema, blood stained pleural fluid or in a case that is not clinically improving despite appropriate treatment.⁷

4. Blood tests 

• Full blood count (FBC), C-reactive protein (CRP), serum electrolytes (U&E), liver function tests (LFT)¹⁰ and blood cultures should be performed:
  • Serial White Cell Count (WCC) and CRP are helpful for monitoring response to therapy.
  • U&E helpful to monitor for increased antidiuretic hormone (ADH) secretion
  • Low serum albumin common in children with pleural empyema
  • A blood culture should be taken although the isolation rate is low (10 - 22%).
• Pneumococcal Polymerase Chain Reaction (PCR) can be considered on EDTA blood in children with empyema with negative blood cultures.¹¹A QuantiFERON-TB-Gold assay may be of use if tuberculosis is likely on clinical and/or epidemiological grounds. In cases of suspected tuberculosis discussion with the infectious diseases (ID) team is recommended.

5. Pleural fluid

• In children with a moderate or large effusion, a sample of pleural fluid should be obtained as early as possible to identify the causative organism. In most instances, the sample can be obtained at the time of chest drain insertion.
• Any pleural fluid that is available should undergo microbiological analysis including gram stain, culture and antibiotic sensitivity testing¹². Fluid should also be sent for cytological analysis as malignant cells may be observed. A lymphocytosis may indicate tuberculosis or malignancy.
• Both pneumococcal antigen testing and pneumococcal PCR can be performed on pleural fluid and have high sensitivity and specificity.^{7, 13, 14}
• In children with pleural effusions who are at risk of tuberculosis (birth or travel to high-incidence country, exposure to index case; symptoms for > 2 weeks), Acid Fast Bacteria (AFB) stains, mycobacterial culture and PCR is recommended on pleural fluid; discuss with ID team.

Pleural fluid and other specimen collections:

Specimen	Tests required
Pleural fluid x 3:  1. Sterile yellow-top cytospin container 2. BACTECTM PEDS PLUSTM blood culture bottle (1-5ml) 3. An EDTA Blood Tube (1-3ml)	On each of the samples: Cell count Gram stain and culture S. pneumoniae PCR+/- **AFB stain, mycobacterial culture and PCR (GeneXpert®)
± Sputum	Microscopy, culture and sensitivity (MCS) +/-**Additional respiratory specimens for AFB stain and mycobacterial culture
± Nasopharyngeal aspirate or throat swab	Respiratory virus PCR
±**Blood	S. pneumoniae PCR +/-**QuantiFERON-TB gold assay.
**If pleural tuberculosis is being considered (birth or travel to high-incidence country, exposure to index case or subacute presentation). Note that pleural TB can be paucibacillary resulting in negative AFB stain and culture. **Isolation in a negative pressure room is required if tuberculosis is being considered. Airborne precautions must be taken at all times, with highest risk during aerosol generating procedures like intubation, obtaining induced sputums and aspiration of pleural fluid.

Management

1. Supportive Therapy

• Oxygen supplementation if hypoxic (oxygen saturation <94%), 
• Fluid therapy 
• Adequate analgesia
• Physiotherapy for assistance with early mobilisation only. 

2. Empiric Antibiotics 

• Please also refer to ChAMP empiric guideline Acute Respiratory Tract Infection and ChAMP Medication Monographs 
  • IV Ceftriaxone 50mg/kg (to a maximum of 2 grams/dose) 24 hourly 
• In severe cases (including necrotising pneumonia) and in children known or suspected to be colonised with MRSA add:
  • IV Vancomycin 15mg/kg (to a maximum initial dose of 750mg) 6 hourly (therapeutic drug monitoring is required)
• Revise antibiotics on the basis of microbiology results. Most empyema is caused by amoxicillin-susceptible organisms.

Special considerations

Discuss the following clinical situations with an Infectious Diseases physician or Clinical Microbiologist:

• TB: **Isolation in a negative pressure room is required if tuberculosis is being considered. Airborne precautions must be taken at all times, with highest risk during aerosol generating procedures like intubation, obtaining induced sputum sample, gastric aspirates and aspiration of pleural fluid.
• For very ill children/admitted to Paediatric Critical Care (PCC)/necrotising pneumonia: discuss with ID on call regarding optimal antibiotics. 
• Geographic risks: If the child resides in the far north of Western Australia, consideration should be given to treating melioidosis (Burkholderia pseudomallei) or Acinetobacter infection, although Streptococcus pneumoniae, Staphylococcus aureus will still be the most likely pathogens. 
• Drug allergy: If there is a significant history of allergy to beta-lactams or vancomycin, alternative antibiotics will be required. 

Review of empiric antibiotics

• Antibiotics should be reviewed after microbiological results are available (blood culture, pleural culture and blood/pleural PCR) and with consideration of the child’s clinical response
• In children in whom no pathogen is identified, empiric intravenous therapy (IV Ceftriaxone +/- Vancomycin) should be maintained until clinical improvement.
  • MRSA nasal swab has high negative predictive value for MRSA pneumonia and may be used to guide de-escalation in culture-negative cases. 15, 16
  • Oral amoxicillin (30mg/kg/dose (to a maximum of 1g) 8 hourly) is the preferred oral step-down agent. If there is a high suspicion of MSSA or MRSA, discuss with ID.
• Most children with proven Streptococcus pneumoniae empyema can be treated with:
  • IV benzylpenicillin: 50mg/kg/dose (to a maximum of 1.2g) 6 hourly and then,
  • Oral amoxicillin: 30mg/kg/dose (to a maximum of 1g) 8 hourly
    • IV Ceftriaxone may be used if reduced susceptibility to penicillin is identified or to facilitate outpatient IV treatment.
• Most children with proven MSSA empyema can be treated with:
  • IV flucloxacillin: 50mg/kg/dose (to a maximum of 2g), 6 hourly and then,
  • Oral cephalexin: 40mg/kg/dose (to a maximum of 1.5g) 8 hourly.
  • Children with MRSA empyema should be discussed with an ID Physician or Clinical Microbiologist as sensitivity of individual pathogens vary.

Duration of antibiotics

• Fever can persist for several days, even on appropriate antimicrobial therapy.
• Children should receive IV antibiotics until afebrile for at least 24 hours. 
• Consideration should be given to inserting a mid-line or Peripherally Inserted Central Catheter (PICC) line at the same time as pleural drainage, to avoid issues with venous access. Refer to CVAD Indications, Referral, Booking and Insertion - Clinical Practice Manual (internal WA Health only).
• Oral antibiotics should be given after discharge for a period of 1-4 weeks, longer if necessary. The length of treatment depends on factors including the severity of the disease, causative organism and complications. 

3. Chest drain versus no chest drain 

• Children with a small effusion and minimal respiratory distress usually respond to antibiotics alone, whereas those with a moderate to large sized pleural effusion and/or signs of respiratory distress or hypoxia often require drainage.

Note:

• Some children with a small pleural effusion, who are being appropriately managed with antibiotics alone, will progress to develop a moderate to large sized pleural effusion requiring drainage. If no clinical improvement at 48hrs and/or deterioration, repeat the CXR and chest ultrasound.
• Importantly, the appearance of loculations on ultrasound does not predict success of chest tube drainage and fibrinolytic therapy.

4. Intrapleural interventions 

• At PCH, chest drain plus fibrinolysis is the preferred option for children/ adolescents with a pleural empyema requiring drainage, unless specific circumstances dictate otherwise.
  • Intrapleural interventions have been associated with significantly shorter hospital stays compared with intravenous antibiotics alone, while instillation of intrapleural fibrinolytics offers benefit beyond simple chest tube drainage in shortening length of hospital stay.¹
• Children with empyema who have a positive blood culture and/or require intensive care are at the highest risk for requiring repeat pleural drainage procedures.¹⁷
• A small pigtail catheter is preferred for chest drainage^21,22 and is inserted either in PCC, Interventional Radiology or Theatre with appropriate analgesia and sedation or general anaesthesia.
• The pigtail catheter should be connected to continuous Under Water Seal drainage (UWSD). However free drainage is preferred for extremely ill children with large effusion.
• Please refer to Chest Drain Management guideline in the Clinical Practice Manual (internal WA Health only).
• There is no evidence that 4 hourly aspiration confers any advantage over UWSD.
• The UWSD should remain clamped for one hour following initial drainage (or once 10mLs/kg pleural fluid has been removed) to reduce the very small risk of re-expansion pulmonary oedema.^2,18
• The UWSD should also be clamped for one hour following the instillation of fibrinolytics.
• If the patient’s clinical status deteriorates at any time (e.g. increased shortness of breath, chest pain, increasing oxygen requirement):
  • Examine the patient
  • UNCLAMP drain if applicable
  • Attempt sterile aspiration of the chest drain
  • Consider an urgent portable CXR. 

Fibrinolytics 

Intrapleural Alteplase (tissue type plasminogen activator, tPA) should be instilled from the outset if the pleural fluid obtained is turbid or if there is evidence of loculations on ultrasound. ^9,18

Dose

• For patients >10 kg, instil alteplase 0.1mg/kg (maximum 6mg) in 1mL/kg Sodium Chloride 0.9% (maximum volume 50mL). Clamp the drain for 1 hour^12,14. Give once daily for 3 days only.
• For patients <10 kg, instil alteplase 0.1mg/kg in 10mL Sodium Chloride 0.9%. Clamp the drain for 1 hour.^12,14 Give once daily for 3 days only.

Minor side effects

• Transient chest pain during instillation and transient blood staining of the pleural fluid. For analgesia, intrapleural bupivicaine 0.25% can be instilled (0.5-1.0mL/kg) at the same time as tPA if significant discomfort ⁹.

Rare cases of immediate hypersensitivity reaction and cases of bleeding have been reported in adults.

Pain

• Pleuritic pain as well as the discomfort of a chest drain may reduce deep breathing and affect the child’s willingness to cough.
• Adequate analgesia is essential to promote comfort and facilitate breathing exercises and mobilisation.

Chest drain removal

• The ongoing requirement for the chest drain should be discussed on a daily basis with the treating medical team and documented in the patient’s medical record.
• The timing of chest drain removal is a clinical decision. It may be useful to repeat the ultrasound when no draining is present to confirm the placement of the drain, its patency or the absence of a significant amount of fluid.
• It is not necessary to await complete cessation of drainage. The chest drain can generally be removed if drainage is less than 1-2mL/kg/24h if the child has clinically improved.
• The chest drain should be removed briskly either while the child performs a Valsalva manoeuvre or during expiration
  • Refer to Chest Drain Management guideline (internal WA Health only) for intercostal catheter removal procedure.
  • Note: Some pigtail catheters require uncoiling prior to removal - ensure type of catheter is identified. See UreSil Pigtail Catheter Removal - Clinical Practice Manual (internal WA Health only) if this type of catheter is used.
• There is no recommendation to complete a CXR as routine practice following uncomplicated chest drain removal.^19,20
  •  However, if the child shows respiratory distress after removal of the chest drain, complete an immediate clinical examination. If a pneumothorax is determined to be one of the differential diagnoses for the clinical signs after chest drain removal, then request a CXR and escalate care in accordance with escalation protocols.

Discharge planning and follow-up

• Patients should be advised they must be followed up as an outpatient until they have fully recovered and their CXR has returned to normal; this can take up to 6 months.⁹ If a patient continues to improve a CXR should not be performed before 4 months after intravenous treatment.
• All patients with suspected or confirmed TB will be managed by the ID team and followed up in the Anita Clayton Centre within 2 weeks of discharge.
• For other patients, an initial outpatient clinic review by the treating medical team should be scheduled for six weeks after discharge to complete, or earlier if required:
  • A thorough physical examination, checking for catch-up growth, and no residual or new complications of the cardiorespiratory and chest-wall musculoskeletal systems.
  • Respiratory function testing and CXR
    • If there is persistent reduced exercise tolerance and poor catch-up physical growth.
    • If there is persistent cough and/or chest pain
  • Routine immune function tests are not necessary, but may be considered in selected cases⁹. Immune studies should be completed if there is a past history of severe, recurrent and/or prolonged episodes of bacterial infection, prolonged and/or poor healing and recurrent boils and/ or abscesses, infection with an unusual pathogen, or infection with a pneumococcal vaccine serotype. Immune studies should be considered if there are persistent symptoms not resolved from the acute episode.
  • In young infants with a pleural empyema secondary to Staphylococcus aureus or Pseudomonas aeruginosa consider a sweat test to exclude cystic fibrosis.

Long term follow up

• CXR - Pleural thickening and underlying consolidation are frequently observed following treatment and, in isolation, do not mean failed therapy. CXR changes (particularly pleural thickening) may persist for 3–6 months following successful treatment
• Lung Function

Most patients make a complete recovery. Management should aim to minimise short-term morbidity (e.g. pain, time to resolution of fever, length of hospital stay).

References

1. Course CW, Hanks R, Doull I. Question 1 What is the best treatment option for empyema requiring drainage in children? Archives of Disease in Childhood. 2017;102(6):588-90.
2. Strachan R.E. , Gulliver T, Martin A, McDonald T, Nixon G, Roseby R, et al. Paediatric Empyema Thoracis: Recommendations for Management. Position statement from the Thoracic Society of Australia and New Zealand 2010.
3. Oyetunji TA, Dorman RM, Svetanoff WJ, Depala K, Jain S, Dekonenko C, et al. Declining frequency of thoracoscopic decortication for empyema — redefining failure after fibrinolysis. Journal of Pediatric Surgery. 2020 2020/01/10/.
4. Derderian SC, Meier M, Partrick DA, Demasellis G, Reiter PD, Annam A, et al. Pediatric empyemas – Has the pendulum swung too far? [Level III] Journal of Pediatric Surgery 2019 2019/12/30/.
5. Pacilli M, Nataraja RM. Management of paediatric empyema by video-assisted thoracoscopic surgery (VATS) versus chest drain with fibrinolysis: Systematic review and meta-analysis. Paediatr Respir Rev. 2019 Apr;30:42-8. PubMed PMID: 31130425. Epub 2019/05/28. eng.
6. Haggie S, Fitzgerald DA, Pandit C, Selvadurai H, Robinson P, Gunasekera H, et al. Increasing Rates of Pediatric Empyema and Disease Severity With Predominance of Serotype 3 S. pneumonia: An Australian Single-center, Retrospective Cohort 2011 to 2018. Pediatr Infect Dis J. 2019 Dec;38(12):e320-e5. PubMed PMID: 31634299. Epub 2019/10/22. eng.
7. Walker W, Wheeler R, Legg J. Update on the causes, investigation and management of empyema in childhood. Archives of Disease in Childhood. 2011;96(5):482-8.
8. Thomson AH, Hull J, Kumar MR, Wallis C, Balfour Lynn IM. Randomised trial of intrapleural urokinase in the treatment of childhood empyema. Thorax. 2002 Apr;57(4):343-7. PubMed PMID: 11923554. Pubmed Central PMCID: PMC1746300. Epub 2002/03/30. eng.
9. Janahi I, and, Fakhoury K. Management and prognosis of parapneumonic effusion and empyema in children. Up To Date 2020 [updated May 5, 2020]. Available from: https://www-uptodate-com.pklibresources.health.wa.gov.au/contents/management-and-prognosis-of-parapneumonic-effusion-and-empyema-in-children?search=Management%20and%20prognosis%20of%20parapneumonic%20effusion%20and%20empyema%20in%20children&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1.
10. Prais D, Kuzmenko E, Amir J, Harel L. Association of hypoalbuminemia with the presence and size of pleural effusion in children with pneumonia. Pediatrics. 2008 Mar;121(3):e533-8. Doi:10.1542/peds.2007-0317.
11. Murphy J, O’ Rourke S, Corcoran M, O’ Sullivan N, Cunney R, Drew R. Evaluation of the Clinical Utility of a Real-time PCR Assay for the Diagnosis of Streptococcus pneumoniae Bacteremia in Children: A Retrospective Diagnostic Accuracy Study. The Pediatric Infectious Disease Journal. 2018;37(2):153-6. PubMed PMID: 00006454-201802000-00009.
12. Balfour-Lynn I, Abrahamson E, Cohen G, Hartley J, King S, Parikh D, et al. BTS guidelines for the management of pleural infection in children. Thorax. 2005;60(Suppl 1):i1-i21. PubMed PMID: PMC1766040.
13. Casado Flores J, Nieto Moro M, Berron S, Jimenez R, Casal J. Usefulness of pneumococcal antigen detection in pleural effusion for the rapid diagnosis of infection by Streptococcus pneumoniae. Eur J Pediatr. 2010 May;169(5):581-4. PubMed PMID: 19806363. Epub 2009/10/07. eng.
14. Harris KA, Turner P, Green EA, Hartley JC. Duplex Real-Time PCR Assay for Detection of Streptococcus pneumoniae in Clinical Samples and Determination of Penicillin Susceptibility. Journal of Clinical Microbiology. 2008;46(8):2751-8. PubMed PMID: PMC2519471.
15. Dangerfield B, Chung A, Webb B, Seville MT. Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia. Antimicrob Agents Chemother. 2014;58(2):859-64. PubMed PMID: 24277023. Epub 2013/11/25. eng.
16. Linfesty D, Manaloor J. Use of MRSA Nasal Swab to Guide Empiric Antibiotic Treatment of Hospital Acquired or Community Acquired Pneumonia in a Pediatric Population. Open Forum Infect Dis. 2017;4(Suppl 1):S502-S. PubMed PMID: PMC5630895. eng.
17. Livingston MH, Cohen E, Giglia L, Pirrello D, Mistry N, Mahant S, et al. Are some children with empyema at risk for treatment failure with fibrinolytics? A multicenter cohort study. J Pediatr Surg. 2016 May;51(5):832-7. PubMed PMID: 26964704. Epub 2016/03/12. eng.
18. Pierrepoint M, Evans A, Morris S, Harrison SK & , Doullet IJ. Pigtail catheter drain in the treatment of empyema thoracis [Level III-3]. Archives of Disease in Childhood. 2002;87(4):331-2.
19.  Johnson B, Rylander M, Beres AL. Do X-rays after chest tube removal change patient management? J Pediatr Surg. 2017 Jan 30. PubMed PMID: 28189452. Epub 2017/02/13. eng.
20. Cunningham JP, Knott EM, Gasior AC, Juang D, Snyder CL, St Peter SD, et al. Is routine chest radiograph necessary after chest tube removal? J Pediatr Surg. 2014 Oct;49(10):1493-5. PubMed PMID: 25280653. Epub 2014/10/05. eng.

Approved by:	CAHS Medication Safety Committee	Date:	Sep 2021
Endorsed by:	CAHS Drugs & Therapeutics Committee	Date:	Oct 2021
		Review date:	Sep 2024

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