Cover PageManuscript type – Review Article Title - Empyema Thoracis in ChildrenName(s) of the author(s) - Dr. Dasmit Singh Khokar Affiliation(s) of author(s) –Prof. of Paediatric Surgery, B.J. Govt. Medical College, PuneCurrent affiliation and affiliation where the work was primarily carried out – Same as aboveName and postal address of corresponding author – Dr. Dasmit Singh Khokar, E – 201, Maestros, Wanawadi, Pune – 411040.Email address(es) – Running title – Empyema Thoracis in ChildrenEMPYEMA THORACIS IN CHILDRENAuthor: Dr.Dasmit Singh KhokarINTRODUCTION: Empyema is a condition in which pus and fluid from infected tissue collects in a body cavity. The name is derived from the Greek word empyein meaning pus-producing (i.e. suppurating). Empyema is most often used to refer to collections of pus in the pleural cavity, but refers to purulent collections in the gall bladder or the pelvic cavity also.A child gets an attack of a febrile illness associated with cough and breathlessness. On examination he is found to be suffering from Pneumonitis and Antibiotics are started. The child starts improving and the fever recedes so the initial response is judged to be good. However, after a few days, the fever returns but this time it is associated with chest pain. This is the classical presentation of Empyema.Empyema Thoracis is defined quite simply as an accumulation of pus in the pleural cavity i.e. pyothorax. It most often occurs as a sequel of Bacterial Pneumonitis but may also occur following trauma, intrathoracic oesophageal perforation or operations on the chest.The mortality may range from 6% to 24% if not treated according to accepted protocols as published by Ala Eldin in 2010.EPIDEMIOLOGY:The risk of empyema in children is around 0.7% to 1.5% in children hospitalized for community acquired pneumonia, although percentages up to 30% have also been reported by Byington et al. The spurt of high incidence in some hospitals is not only due to an endemically high invasive serotype but also overdiagnosis of small parapneumonic effusions. In the preantibiotic era, the commonest organisms were Pneumococci and Streptococci. In the 1950s and 1960s Penicillin resistant Staphylococci were more common. These days, Streptococci pneumoniae, Staphylococcus aureus, and Haemophilus influenzae predominate. Mycobacterium tuberculosis, anaerobic bacteria and fungal infections are also seen on occasions especially in immunocompromised paediatric patients.Le Monnier in an analysis of 78 children with community acquired pleural empyema, found no micro-organism in 27% of patients, Streptococcus pneumoniae in 51%, Streptococcus pyogenes in 9% and Staphylococcus aureus in 8%. This significantly differs from adults where negative pleural-fluid cultures were seen in 54% of patients and Streptococcus pneumoniae was grown in only 8% of patients as reported by Maskell NA et al.AETIOLOGY OF EMPYEMA:Empyema in the paediatric population usually results as a complication of pneumonia. However, it can also be caused by penetrating trauma of the chest, rupture of the oesophagus, as a complication after lung or other thoracic surgeries or unsterile thoracocentesis or insertion of a chest tube. It can also occur due to a tracking through of a subdiaphragmatic, liver or paravertebral abscess.PATHOGENESIS OF EMPYEMA:The pleural space has fluid which is in continuous circulation. The quantity is normally small (0.3 ml/kg body weight). Lymphatics can absorb plenty of extra fluid on a regular basis. When the delicate balance between pleural fluid secretion and absorption is disturbed, it results in pleural effusion. In response to an infection, the lung and vascular tissue initiate an immune response and the pleura gets inflamed. The increased permeability of the vessels allows migration of inflammatory cells into the pleural space. The process of migration of these neutrophils, lymphocytes and eosinophils is mediated by cytokines like interleukin IL-1, IL-6, IL-8, Tumour necrosis factor (TNF)-alpha and Platelet activating factor. These are released by the mesothelial cells of the pleura. This causes the exudative stage of pleuricy and effusion. This process is followed by the fibropurulent stage. The resultant Polymorphonuclear migration occurs along with the activation of the coagulation cascade which leads to a diminishing fibrinolysis. This allows Fibrin to get deposited within the pleural space leading to formation of septae and loculation. These systematic responses of the body’s defence mechanisms to an infection take place in three phases resulting in 4 stages of empyema:Exudative response: When infection of the pleura occurs, there is outpouring of thin fluid with a low cellular content. This is the immediate response. The quantity is quite small. This is the Stage of Exudative Pleurisy or Stage I EmpyemaFibrinopurulent response: Large quantity of fibrin rich fluid with Neutrophils fill up the pleural space. The lung starts getting compressed. As more and more cells are added into the fluid, the fluid gets thicker and attains the characteristic of pus. The lung becomes progressively less expandable. Loculation also begins and progressively increases. This includes two stages of empyema ; Stage II of Established Empyema and Stage III of Late Organising EmpyemaOrganizing response: As a last attempt at healing, the body resorts to laying down of fibrotic tissue. Fibroblasts grow into the exudate on both the surfaces of the pleura. The fibrosis of the visceral pleura forms an encasement over the lung and progressively reduces the expansile capacity of the lung. The fibrosis of the parietal pleura reduces the calibre of the intercostal spaces leading to reduced expandability of the chest wall, shortening of the ipsilateral chest and also scoliosis. Even if infection is somehow controlled at this stage, permanent disability with scoliosis, compromised lung function, reduced exercise tolerance and growth failure may occur. This is Stage IV or the stage of Chronic Empyema.In olden days each stage would last 2 to 3 weeks so Stage IV Empyema would be seen in chronic cases only after 4 to 12 weeks. With the changing trends of pathogenicity of organisms and antibiotic resistance patterns, nowadays each stage may be as short as a few days and pleural thickening may be evident within 10 days.Empyema Severity Scoring System has been proposed by Hoff et al but is not very useful for planning the treatment. They based it on the pleural fluid characteristics, chest radiography findings and type of infection. Although the pleural fluid investigations are good markers, this score utilized severity on a chest radiograph alone which is not accurate.CLINICAL PRESENTATION:The clinical history and examination findings are quite characteristic. The worsening Pneumonia is fairly apparent with the increasing or resurgence of chest symptoms and signs. In addition, abdominal pain, abdominal distention due to paralytic ileus and signs and symptoms of Septicemia may complicate the basic pathology. Diminished breath sounds and dullness on percussion clinch the diagnosis.Initially, during the phase of Simple empyema, wherein the pus is entirely liquid, the patient presents with fever, dry cough, tachypnoea, chest pain and loss of appetite.Complicated or Complex empyema occurs in the later stage of the illness. The pus when organized and loculation present, the child will have high spiking, remittent or intermittent fever, difficulty in breathing, increasing chest pain, weight loss and decreased breath sounds. It may also be associated with necrotising pneumonitis with the formation of a bronchopleural fistula with expectoration of copious, foul smelling sputum. This needs more aggressive treatment and timely surgery will be necessary to cure the child.Rarely, the pleural collection may herniate out through the intercostal space, a condition called Empyema necessitans or Empyema necessitatis. It can form a subcutaneous abscess, cause osteomyelitis or even involve other organs like Oesophagus, breast, retroperitoneum, peritoneum, pericardiac and paravertebral regions. It may eventually rupture through the skinINVESTIGATIONS: X-RAY OF THE CHEST: is the most important diagnostic investigation. Besides the AP or PA view, an additional decubitus view was used in the pre-Ultrasound era for confirming the presence of fluid in the pleural space. In the early Exudative phase, the fluid flows easily in the decubitus film. In advanced stages, the exudate becomes a solid mass of fibrin and does not move with change of position. In the Fibrinopurulent phase, loculations are characteristic. Air-fluid levels within the locules in the pleural space, suggests Anaerobic organisms or communication with the airways. Staphylococcal empyema may be accompanied by Pneumatocoels within the lung parenchyma. These represent dissection of air along the peribronchial and alveolar interstitium with ballooning of the thin-walled sac. Occasionally pneumatocoels are also seen in Klebsiella empyema.Thickened pleura is sometimes apparent by the underlying compression of the lung. Consolidation and collapse of the lung can indicate the cause. Erosion of the ribs or scoliosis are additional indicators of the disease process.DIAGNOSTIC THORACENTESIS: Diagnostic Chest tapping should be performed in all patients and the fluid sent for Gram stain, Biochemical estimation and Culture and Sensitivity.International Pediatric Endosurgery Group IPEG has provided the guidelines.IPEG GUIDELINES FOR DIAGNOSING EMPYEMA:One or more of the following;* PH < 7.2* GLUCOSE < 40 MG/DL* LDH >1000 IU/DL* PROTEIN > 2.5 G/DL* WBC > 500/µL* SPECIFIC GRAVITY GREATER THAN 1.018* THICK OPAQUE OR CLOUDY FLUID, * POSITIVE CULTUREThese values differentiate Empyema from a transudative sympathetic effusion.ULTRASONOGRAPHY: Ultrasound has emerged as a very useful tool in the management of Empyema. In the early stages it is very sensitive in diagnosing the presence of fluid in the pleural space. It serves as a useful guide for thoracocentesis, inserting an ICD safely; preventing injury to the underlying lung and other structures. It is also quite sensitive in diagnosing multiloculation of the fluid.CT SCAN: A High Resolution CT Scan of the thorax is also a very useful investigation at the later stages when a surgical intervention is being contemplated. It helps to determine the pathological anatomy to aid surgery. Both Lung windows and mediastinal windows are necessary to identify the pleural collection, thickness of the visceral and parietal pleura, presence of air within the pleural collection, parenchymal necrosis, air bronchogram, lung collapse, pneumatocoels etc.TREATMENT:The role of surgery in the treatment of lung infections is limited to those patients in whom despite the defence mechanisms, supportive treatment and appropriate antibiotics, a focus of infection and lung collapse still remains.Conventional treatment of Empyema:Traditionally, from the standpoint of treatment, Empyema management was divided into the following categories:Stage I : Exudative Pleurisy: Symptoms are present for 2 to 3 weeks. Since the fluid is quite thin and transudative, aspiration of the fluid is followed by complete expansion of the lung. Appropriate Antibiotics and supportive therapy including Nebulisation, Humidification, Bromhexine, Bronchodilators, Oxygen when needed, Ventilatory support if required, should also be instituted.Stage II : Established Empyema: Symptoms are present for 3 to 6 weeks. The fluid is thick and only an Intercostal tube drain (ICD) can drain out the fluid. In case a thin looking fluid is reported as an exudate according to the IPEG guidelines, then also and ICD should be inserted.This form of therapy would be sufficient in a majority of patients, but as reported by Ferguson, 15 to 40 percent of patients would require surgical drainage of the infected pleural space because of inadequate drainage due to loculations forming within the empyema.Stage III : Late organising Empyema: Symptoms are present for 6 to 9 weeks. The tenacious purulent exudate and presence of loculi, tend to block the free drainage of pus through an ICD. These cases will need a Thoracotomy with surgical Debridement followed by an ICD to allow the lung to expand. Mild pleural thickening will resolve over a period of time if the infection is controlled and the lung expands.Stage IV : Chronic Empyema: Symptoms are present for 9 to 12 weeks. The lung is encased in thick fibrous tissue which invades the visceral and parietal pleura. This thickened pleura is not only resistant to antibiotics but also does not allow the lung to expand. Thoracotomy and Decortication of the lung will be required at this stage to salvage the patient.It must be noted that the duration of symptoms as related to the stage has undergone an immense change in the present day scenario. Each stage may be as short as 4 to 7 days. This depends upon the body’s defence mechanisms, virulence of the bacteria or other organisms, improper treatment received, combination of organisms producing the disease etc.Other Modalities of treatment: Steroids have been used when early loculation has occurred to prevent the long term sequelae of chest wall fibrosis. The response is unpredictable and better modalities are now available.Fibrinolytic enzymes injection into the ICD have also been used but a favourable response is seen only in very early organising Empyemas and it prolongs recovery when compared to Thoracoscopy.Chest irrigation with the help of two catheters in the chest with instillation of Saline through one and the other acting as an outlet drain. This therapy is found to be useful only when there is single cavity containing pus. This can be achieved by an ICD alone hence not used nowadays.Thoracoscopic treatment of Empyemas (Video Assisted Thoracoscopic Surgery or VATS):The increasing use of Thoracoscopy has changed the management of Empyema immensely. It is now considered the modern-day answer to the prevention of a Thoracotomy. With increasing expertise of Paediatric Surgeons trained in Thoracoscopic surgeries, this modality of therapy could be put to great advantage.Advantages include: High margin of safetyEasy to performThe huge unsightly scar of a thoracotomy is preventedRecovery is fast with minimal morbidity and mortalityEquipment is readily available in most Institutions (same as Laparoscopic Surgical equipment)Relatively inexpensiveReduced hospital stayConsiderably reduced duration of Antibiotics Disadvantages include: Early referral is extremely important for a good resultThick, fibrous pleura and Bronchopleural fistula are not easily amenable to thoracoscopic decortication or surgery Technical expertise is required to perform it well The ideal time of performing a Thoracoscopy is when the fluid just begins to get loculated.This can be recognised by the following symptoms and signs:No reduction of fever inspite of an ICD and higher or appropriate antibioticsAir entry not improved inspite of an ICDLung not expanding even after adequate treatmentContinued drainage of pus through the ICDAppearance of loculi in Xray chest, USG of the chest or CT Scan of the chestThe time period for trial of the primary therapy instituted is not fixed, but a rough guideline would be about 2 to 4 days of treatment with ICD and Antibiotics. If the improvement is not adequate, then Thoracoscopy should be considered.A common error made is repeated tapping of pus from the pleural cavity instead of inserting an ICD. Any exudative report of pleural fluid is an early indication for insertion of an ICD. It should be emphasised that any patient who needs repeated tapping, in fact, needs an ICD. An ICD placed early can prevent loculation of the pus in the pleural cavity. Once loculation is suspected, the patient should be referred for consideration of Thoracoscopy.A timely inserted ICD should prevent a thoracoscopy.A timely performed thoracoscopy should prevent a thoracotomy.At Thoracoscopy, with the patient in lateral position under GA, one, two or three 5 mm and 3 mm ports are inserted into the chest. Chest debridement is carried out, thick and thin organized floccules of pus evacuated, loculi are broken, thickened pleura is peeled off and excised, adequate expansion of the lung is confirmed, an ICD is placed and the port incisions are sutured up. The average post operative hospital stay is 5 days and the child is discharged subsequently on oral antibiotics.It is now a well recognised fact that the Hospital stay and the total Cost of therapy is extremely favourable to the patient. This fact, coupled with the reduced morbidity and mortality of the child with empyema has led to an enormous increase in the usage of Thoracoscopic Surgery for an effective treatment of Empyema.Thus, while the basic principles of Empyema management have remained the same, the modalities of management have improved considerably thereby effectively tilting the odds in favour of the patients afflicted by this debilitating disease.THUMB RULES EXTRACTED FROM THE BTS GUIDELINES FOR THE MANAGEMENT OF PLEURAL INFECTION IN CHILDREN as published by Balfour-Lynn et al:Clinical PictureAll children with parapneumonic effusion or empyema must be admitted to hospitalIf a child remains pyrexial or unwell 48 hours after admission for pneumonia, a parapneumonic effusion/empyema must be excludedDiagnostic imagingPostero-anterior or Anteroposterior radiographs should be taken; there is no role for a routine lateral radiographUltrasound must be used to confirm the presence of a pleural fluid collectionUltrasound should be used to guide thoracocentesis or drain placementChest CT Scans should not be performed routinelyDiagnostic microbiology:Blood cultures should be performed in all patients with parapneumonicWhen available, sputum should be sent for bacterial cultureDiagnostic analysis of pleural fluid:Pleural fluid must be sent for microbiological analysis including Gram stain and bacterial culture.Aspirated pleural fluid should be sent for differential cell count.Tuberculosis and malignancy must be excluded in the presence of pleural lymphocytosisIf there is any indication the effusion is not secondary to infection, consider an initial small volume diagnostic tap for cytological analysis, avoiding general anaesthesia/sedation whenever possibleBiochemical analysis of pleural fluid is unnecessary in the management of uncomplicated parapneumonic effusions/empyemaDiagnostic bronchoscopy:There is no indication for flexible bronchoscopy and is not routinely recommendedReferral to tertiary centre:A respiratory paediatrician should be involved early in the care of all patients requiring chest tube drainage for a pleural infectionConservative management (antibiotics + simple drainage) Effusions which are enlarging and/or compromising respiratory function should not be managed by antibiotics aloneGive consideration to early active treatment as conservative treatment results in prolonged duration of illness and hospital stay.Repeated thoracocentesis:If a child has significant pleural infection, a drain should be inserted at the outset and repeated taps are not recommendedAntibiotics:All cases should be treated with intravenous antibiotics and must include cover for Streptococcus pneumoniaeBroader spectrum cover is required for hospital acquired infections, as well as those secondary to surgery, trauma and aspirationWhere possible, antibiotic choice should be guided by microbiology resultsOral antibiotics should be given at discharge for 1 – 4 weeks, but longer if there is residual disease. Empyema will generally require antibiotics for 6 weeks,Chest drains:Chest drains should be inserted by adequately trained personnel to reduce the risk of complicationsUltrasound should be used to guide thoracocentesis or drain placementIf general anaesthesia is not being used, intravenous sedation should only be given by those trained in the use of conscious sedation, airway management and resuscitation of children, using full monitoring equipmentLarge bore surgical drains should also be inserted at the optimum site suggested by ultrasound, but preferentially placed in the mid-axillary line through the “safe triangle”Neither substantial force nor a trocar should be used to insert a drainA chest radiograph should be performed after insertion of a chest drainAll chest tubes should be connected to a unidirectional flow drainage system (such as underwater seal bottle) which must be kept below the level of the patient’s chest at all timesA bubbling chest drain should never be clampedA clamped drain should be immediately unclamped and medical advice sought if a patient complains of breathlessness or chest painThe drain should be clamped for 1 hour once 10 ml/kg are initially removedWhen there is a sudden cessation of fluid draining, the drain must be checked for obstruction (blockage or kinking) by flushingThe drain should be removed once there is clinical resolutionIntrapleural fibrinolytics:Intrapleural fibrinolytics shorten hospital stay (in comparison to those cases treated without it) and are recommended for any complicated parapneumonic effusion (thick with early loculations) or empyema (overt pus) especially in medical facilities which lack the infrastructural resources for Video Assisted Thoracoscopic Surgeries or VATS.There is no evidence that any of the three fibrinolytics are more effective than the others, but only urokinase has been studied in a randomized controlled trial in children so is recommendedUrokinase should be given twice daily for 3 days (6 doses in total) using 40,000 units in 40 ml of 0.9% saline for children weighing 10 kg or above and 10,000 units in 10 ml of 0.9% saline for children weighing under 10 kgSuccess rate ranges from 24% to 78% only, that too in early stages as reported by Hoff et al.Surgery (VATS or Thoracotomy with Decortication):Failure of chest tube drainage, antibiotics and fibrinolytics should prompt early discussion with a paediatric surgeonPatients should be considered for surgical treatment if they have persisting sepsis in association with a persistent pleural collection despite chest tube drainage and antibiotics.Coote et al reported in the Cochrane Systematic Review on surgical versus non-surgical management of empyema in a randomized trial which studied immediate VATS vs. intrapleural streptokinase for 3 days instilled into a chest. The surgical group had a much higher primary treatment success (10/11 patients) and all streptokinase medical failures (5/9 patients) were salvaged by VATS without requiring thoracotomy. Surgical patients also had a shorter drainage (5.8 v 9.8 days) and a shorter hospital stay (8.7 v 12.8 days). The results of this early study threw light on the success rate of VATS although the sample size was small. VATS should be the treatment of choice for Loculated Empyema and early thickened pleuraLate Organized empyema with grossly thickened pleura in a symptomatic child will require thoracotomy and decorticationA lung abscess coexisting with an empyema should not normally be surgically drainedNecrotising Pneumonia should be gently debrided during VATSA small bronchopleural fistula remaining after VATS rapidly closes as the remaining lung expandsProgressive and slow withdrawal of the ICD can also help in non-operative management of a Bronchopleural fistula after an ICD or VATS has allowed the lung to expand.Bronchopleural fistula can be sutured during thoracotomyOther management:Antipyretics should be given when necessaryAnalgesia is important to keep the child comfortable, particularly in the presence of a chest drainChest physiotherapy is not beneficial and should not be performed in children with empyema who cannot cough.Secondary scoliosis noted on the chest radiograph is common but transient; no specific treatment is required but resolution must be confirmedFollow up:Children should be followed up after discharge until they have recovered completely and their chest radiograph has returned to near normalUnderlying diagnoses – for example immunodeficiency, cystic fibrosis- may need to be consideredFor further reading:Ala Eldin H.Ahmed and Tariq E. Yacoub: Clin Med Insights Circ Respir Pulm Med. 2010; 4 : 1 – 8.Balfour-Lynn IM, Abrahamson E, Cohen G, Hartley J, King S, Parikh D, Spencer D, Thomson AH, Urquhart D (2005). "BTS guidelines for the management of pleural infection in children". Thorax. 60 (Suppl 1): 1–21.Byington CL, Spencer LY, et al (2002). "An epidemiological investigation of a sustained high rate of pediatric parapneumonic empyema: risk factors and microbiological associations". Clinical Infectious Diseases. 34 (4): 434–40. Coote N. Surgical versus non-surgical management of pleural empyema(Cochrane Review). In: The Cochrane Library, Issue 1. Chichester, UK: JohnWiley & Sons, 2004.Ferguson AD, Prescott RJ, Selkon JB, Watson D, Swinburn CR (April 1996). The clinical course and management of thoracic empyema. QJM. 89 (4): 285–9.Hoff SJ, Neblett WW, et al. Postpneumonic empyema in childhood: selecting appropriate therapy. J Pediatr Surg. 1989;24:659–63. Le Monnier A, Carbonnelle E, et al (2006). "Microbiological diagnosis of empyema in children: comparative evaluations by culture, polymerase chain reaction, and pneumococcal antigen detection in pleural fluids". Clinical Infectious Diseases. 42 (8): 1135–40.Maskell NA, Davies CW, Nunn AJ, et al (2005). "U.K. controlled trial of intrapleural streptokinase for pleural infection". New England Journal of Medicine. 352 (9): 865–74.Prema Menon, Ravi Kanojia et al: Empyema Thoracis: Surgical management in children. J Indian Assoc Pediatr Surg 2009 Jul-Sep; 14(3): 85-93Strachan, Roxanne E et al. “Bacterial causes of empyema in children, Australia, 2007-2009.” Emerging infectious diseases vol. 17,10 (2011): 1839-45.Wait MA, Sharma S, 2.
