Surgical Infections III - Thoracic Empyema
This Review is part of a series dealing with Surgery and infection. Future reviews in this series will discuss Surgery and AIDS, wound infection, etc.
| References |
| Questions |
Introduction
Both in Africa and in the West, surgeons are often asked by our medical colleagues
to drain pleural effusions through the insertion of chest tubes. In Africa,
the most common reason for such a request is the post-pneumonic infected effusion
or empyema. In the majority of cases the primary care is left to the medical
service. While chest tubes are often sufficient to manage this problem, in
certain cases the infection may require more sophisticated therapy. Therefore,
it is incumbent on the surgeon to understand, in detail, the classification,
pathophysiology, diagnostic and therapeutic approaches to pleural space infections
(PSI).
This review will concentrate on the post-pneumonic empyema including those
associated with tuberculosis and HIV disease. It will deal briefly with post-traumatic
pleural infections but not with those occurring after thoracic resection.
For these the reader is referred to the following Reviews. (1
; 2) It will review the clinical presentations and range
of infectious agents as well as discuss the new therapeutic approaches of
video-assisted thoracic surgery (VATS) and fibrinolysis, which have impacted
the modern approach to loculated and chronic empyemas. Finally it will discuss
the role of various surgical modalities in the treatment of complex empyemas.
Pleural Effusions – Classification
Three very good reviews outline the classification and approach to the patient
with a pleural effusion. (3 - 5) Although
pleural effusions can be diagnosed through physical examination (dullness
to percussion, decreased breath sounds and vocal fremitus, shift of the trachea),
they are most commonly found on chest xrays. A standard upright posteroanterior
chest xray can detect 150 ml of fluid and the costophrenic angle is blunted
with up to 500 ml. The lateral decubitus chest ray is particularly sensitive;
if there is layering of fluid 1 cm in thickness the effusion is accessible
via thoracentesis - the standard diagnostic test.
Pleural effusions are first classified as transudates or exudates. Transudates,
commonly a result of congestive heart failure, nephrotic syndrome or cirrhosis,
are generally clear and straw coloured. Exudates occur with parapneumonic
effusions, malignancy, tuberculous pleurisy, pulmonary embolism, collagen
vascular disease, pancreatitis and other conditions. Transudates and exudates
are distinguished on the basis of their protein content. An exudate is characterized
by a protein content > 3.0 g/dL and LDH >200, but pleural/serum ratios
are more accurate: protein >0.5; LDH > 0.6.(6) Sadly
these tests are not available in every African hospital. Measurement of cell
count, pH and glucose level and culture of the fluid are particularly important
in infectious effusions (see below). Cytologic examination is important in
the diagnosis of malignant effusions. Pleural biopsy may play a role. (7)
Porcel (8) examined the characteristics of large or massive
effusions in 153 patients and found that most were secondary to infections
or malignancy.
Empyema – Infected
Effusions
Para-pneumonic exudative effusions occur in up to 50% of pneumonias. Pleural
space infections – empyemas need to be distinguished from these by the
presence of an infectious agent, (although culture may be negative in up to
30% of PSIs), their ability to cause morbidity and their need for specific
treatment. A number of excellent recent reviews discuss the nature and management
of thoracic empyema. (9 - 13) The majority,
40-60%, are post-pneumonic. Infections after thoracic surgery and trauma make
up the rest, with about 10% being idiopathic. A rare cause is the pyothorax
associated lymphoma arising in chests treated with chronic pneumothorax. (14)
Empyemas have been divided into three stages: 1st or exudative, 2nd or fibrinopurulent
and 3rd consolidative or chronic stage. Complex empyemas are multi-loculated.
In the exudative stage drainage may not be necessary. However if frank pus
is present or culture or gram stain is positive; if pH < 7.2, glucose <
35mg/dL, or LDH >1000 IU/L, then drainage is mandatory and should not be
delayed. Azoulay et al (15) used reagent sticks to measure
pH, protein content and leukocyte esterase levels and found good correlations
with standard laboratory methods and ability to distinguish infectious exudates.
This study is particularly relevant to the African context where laboratory
facilities are practically non-existent. Where tests such as these may not
be available it is better to err on the side of drainage.
Drainage is the sine qua non of empyema treatment. In the early stages before
fibrinous deposits have fixed the lung to the underlying chest wall, drainage
to an underwater seal must be maintained. In later stages open drainage with
rib resection has traditionally been used. Undrained, delayed or inadequately
drained pus results in pleural scarring and fibrosis, persistence of the lung
collapse and maintenance of the infection. (16) A chronic
empyema, which begins about 6 weeks after infection, requires surgical intervention
aimed at obliterating the cavity either by VATS or thoracotomy with decortication
of the lung and removal of the pleural peel, plus or minus lung resection,
or with thoracoplasty bringing the chest wall down to the lung. Bronchopleural
fistula complicates the decision process.
Microbiology
A wide range of infectious agents have been shown to cause PSI. While culture
of pleural fluid must always be done, blood cultures should also be taken
in febrile patients. Streptococcus pneumoniae (17) and staphylococcus
aureus (18) are generally the most common pathogens in children,
but anaerobes (19) and gram negative aerobes such as Klebsiella
(20) may predominate in adults. Unusual organisms like Salmonella
(21), Yersinia (22), Gemella (21)
and fungal disease (24) may cause empyemas; hydatid cysts
of the liver may rupture into the pleural space (25); even
trichomonas (26) has been isolated. Tuberculous pleurisy
is an important entity that will be discussed below.
Imaging
While the PA chest xray is the standard tool in the diagnosis of pleural effusion
and empyema, other imaging techniques play an important role. (27)
One of the major problems in the treatment of empyema is its failure to resolve
with tube thoracostomy. (see below) This may occur as a result of
the formation of septae and loculations in the pleural space resulting in
multiple, non-communicating cavities. Ultrasound plays an important role in
the diagnosis of this septation and can predict the success of simple thoracostomy
and the need for alternative measures. (28) Image guided
drainage can also be carried out.(29 ; 30)
CT scan identification of a pleural peel accurately predicts the need for
surgery. (31)
Post-Pneumonic Empyema
(32)
Interest has focused on which patients develop PSI. (33)
Multiple factors including underlying patient health, bacterial virulence
and promptness of drainage determine clinical outcome in PSI. (34
;35) In one retrospective study delaying drainage for 3
days after recognition was associated with an increase in mortality rate from
3% to 16%. Cell mediated immunity is depressed in empyema patients. (36)
Treatment failure has also been associated with the presence of antibiotic
resistant organisms (37) and with delay in diagnosis and
referral.
Children
In the last 10 years, only two reports in English are available from Africa
on the treatment of post-pneumonic PSI in children.(38 ;39)
In both the mean patient age was five. Fever, cough, dyspnea were the standard
presentations with radiologic evidence of pleural effusion. Pneumococci or
staphylococci were the most common organisms isolated. No patient in the Ethiopian
study and one in the Nigerian study received thoracotomy and decortication.
This may indicate lack of or inadequate utilization of surgical services.
The mortality rate ranged from 7-16%. In a recent study of 265 children with
empyema from India (40), staphylococcus was the most common
organism. Tube thoracostomy failed in 21% of cases classified as fibrinopurulent.
Decortication was required in 25% of all thoracotomies, particularly when
surgery was delayed. Eastham et al (17) present their experience
with 47 children from north England. In 75% of cases an infectious agent was
identified of which 86% were pneumococcci, although this diagnosis could only
be made through the isolation of bacterial DNA. The prior prescription of
antibiotics in 96% of cases may have played a role in the lack of positive
pleural cultures. PSI complicates 2-8% of pneumonias in children in the US.
Schultz et al (41) report on 230 children in Texas over
a 10 year period. 32% of pleural cultures were positive. The development and
use of pneumococcal vaccine resulted in staphylococci being the most common
organism isolated in the later period. Antibiotic resistance was a developing
feature.
Adults
Nadeem et al (42) reported on 105 consecutive patients older
than 10 years presenting to a Thoracic Surgical Unit in Peshawar, India. The
mean duration of symptoms was 6 weeks with 38% having had an unsuccessful
drainage prior to admission. The majority of patients required open surgery
with a mortality rate of 7%. Cheng (43) reported on 72 patients
from California treated with a non aggressive protocol with a mortality rate
of 6%. Tsai et al (44) compared empyema in Tawainese adults
older than 65 years with younger patients. The older patients had similar
mortality rates, but higher morbidity, rates of fungal infection and an increased
risk of associated malignancy.
Tuberculous pleurisy and empyema
Tuberculous pleurisy and empyema are discrete clinical entities requiring
specific approaches. Pleural effusions may complicate up to 30% of cases of
tuberculosis in Africa. (11 ;12) The association
between AIDS and TB is well known. In tuberculous pleurisy the effusion occurs
as part of the primary infection. The duration of symptoms is usually long
with a mean of 4 months. Chest xray may or may not show typical findings of
TB. Early on the pleural fluid shows a typical exudative character, later
lymphocytes may predominate. Pleural levels of adenosine deaminase (ADA) are
increased. Sputum may be positive for AFB in about 50% of cases. Mycobacteria
are cultured in less than 50% of samples of pleural fluid; the yield is improved
with histology and culture of pleural biopsies. While tuberculous pleurisy
may resolve spontaneously over several months, ATB therapy is indicated.
Tuberculous empyema is a much more serious condition with massive contamination
of the pleural cavity as a complication of pulmonary tuberculosis. The pleural
fluid is purulent and AFB are more commonly identified. A bronchopleural fistula
may be present. Al Kattan et al (45) report on 26 patients
from Saudi Arabia. The empyemas were classified using pleural aspirates and
CT scan findings. Aspiration and tube thoracostomy were adequate for exudative
collections alone, but more advanced stages required other interventions.
Decortication, pulmonary resections and open thoracostomies are important
treatment modalities. Olgac et al (46) recommended decortication
alone in patients with prolonged lung collapse and pleural infection secondary
to tuberculosis.
HIV-positive patients
It is uncertain whether PSI is more common in HIV-positive patients but it
is more serious. Borge et al (47) reported on 23 HIV-positive
patients who were all intra-venous drug users. Most empyemas were secondary
to community-acquired pneumonia with staph aureus and gram negative bacilli
being the most common organism. Closed thoracostomies and fibrinolytic therapy
was used. Patients with AIDS had higher risk of bronchopleural fistula and
prolonged hospital stay. Khwaja (48) found that AIDS patients
with CD4 counts < 200 had more complex empyemas requiring open drainage
and decortication.
Post-Traumatic Empyema
Tube thoracostomy is appropriate and necessary treatment for traumatic pneumothorax
and hemothorax. (49) Empyema and pleural fibrosis are significant
risks in undrained hemothoraces. Bailey (50) reviewed complications
of tube thoracostomy. Empyema occurs in about 2%. Maxwell et al (51)
found that post-traumatic empyemas were related to the degree of underlying
(particularly penetrating) lung injury and duration of tube placement. Concurrent
antibiotics did not appear to be preventative.
Treatment
Antibiotics
Antibiotic therapy, active against the common pathogens causing PSI, should
be initiated parenterally in all cases of empyema, before culture reports
are available. Since these include pneumococcus, staph aureus, anaerobes and
gram negatives, a broad spectrum penicillin with beta-lactamase resistance
along with an anaerobic agent is a good choice. Amoxicillin/clavulinate or
cefuroxime plus metronidazole are reasonable combinations. Palacios et al
(52) found that cefuroxime was as effective as dicloxacillin/chloramphenicol
in children. Teixeira et al (53) found significant differences
in pleural antibiotic levels among various agents. Aminoglycosides, which
are inactivated in pus and low pH, should probably be avoided. Paganini et
al (54) found that PSI from penicillin resistant organisms
was no more virulent. Surgeons should be aware of local antibiotic resistance.
Nutritional support
Empyema patients are often nutritionally depleted. Nutritional assessment
and support is vital to the resolution of the underlying infection.
Drainage
In 2000 the American College of Chest Physicians published a Consensus Statement
on the treatment of parapneumonic effusions. (55) They divided
patients into 4 groups, on the basis of risk of poor outcome and used quantity
of fluid, presence or absence of loculation, fluid culture reports, and pH
of pleural fluid, to develop recommendations regarding the necessity of drainage.
Basically if the effusion is small and free flowing, the culture negative
and the pH>7.2 drainage is unnecessary (groups 1 & 2). If the effusion
is greater than ½ hemothorax OR loculated OR culture positive OR pH<7.2
drainage is recommended (groups 3 & 4).
The main cause of treatment failure, morbidity and mortality in empyema is
the development of loculated, undrained pus resulting in pleural scarring,
fibrosis and chronicity of infection requiring surgical intervention. The
objective of treatment is not only to resolve the infection but prevent this
progression to chronicity. To succeed prompt and complete evacuation of infected
fluid must be achieved.
A number of treatment modalities are available. These include:
Thoracocentesis – Repeated ultrasound guided thoracocentesis has been compared to closed thoracostomy in a small study. (54) Excluding patients with massive empyema resulting in mediastinal shift, both modalities had similar number of treatment failures. Intra-pleural fibrinolysis was used as deemed necessary in both groups. I believe that this modality should only be used in the earliest and most responsive cases and mandates extreme vigilance.
Closed thoracostomy –
Closed chest tube drainage has been the standard first line therapy for empyema
throughout the last century. Large bore tubes have historically been inserted
to underwater seal and suction applied. Used with antibiotics alone, these
have a significant failure rate of up to 50%. Repeated chest xrays must be
taken to ensure prompt evacuation of all fluid. Chest tubes should not normally
be clamped. If drainage ceases a chest xray should be taken to assess if there
is kinking or if residual fluid remains. The tube can be irrigated. If the
tube is malfunctioning or drainage less than 100 in 24 hours, it should be
removed. A simple suture for closing thoracostomy incisions has been described.
(55) If significant fluid remains the next level of intervention
should be undertaken.
Huang et al (56) determined that pleural fluid WBC<6400/uL
and loculation were independent predictors of failure of tube thoracostomy.
Pierrepoint et al published a study using historical controls which showed
pigtail catheters to be superior to standard chest tubes in preventing the
need for surgical intervention.(30)
Fibrinolysis –
The intra-pleural instillation of fibrinolytic agents has been used to breakdown
loculations. Schiza et al (59) reviewed the agents used.
Generally 250,000 IU of streptokinase is diluted in 20-100 ml saline and instilled
via the chest tube which is clamped for 2-4 hours. Twice daily instillations
for three days are routine. This regime is applicable for children as well.(60)
Fever and allergic responses have been the most common side effects. Bleeding
complications are unusual. The treatment does induce the presence of anti-streptokinase
antibodies. (61)
The efficacy of fibrinolytics has been carefully scrutinized. Cameron et al
(62) examined the published RCTs for the Cochrane Database
and concluded there was insufficient evidence to recommend their use. This
lack of evidence has recently been resolved with the publication of the MIST
study from the UK. (63) This large, multicenter RCT in adults
clearly showed no difference between saline and streptokinase chest tube instillation
in terms of treatment failures, need for surgery or mortality. Need for surgery
and mortality rate were similar in both groups at 15%. A recent RCT from India
showed no difference in short term results between streptokinase and saline
(none of their patients failed) but a significant reduction in need for delayed
surgery in those with multiloculated empyemas who had received streptokinase.
(64) Another RCT from South Africa showed a significant
improvement in treatment success and avoidance of surgery in streptokinase
treated patients after seven days. (65) A recently published
RCT from Greece also showed an improved success rate and lowered mortality
rate with fibrinolysis compared to tube drainage alone. (66)
While the MIST study certainly casts doubt on the value of fibrinolysis, further
RCTs and meta-analyses can be anticipated. Although fibrinolysis may not be
useful, agents such as DNase, which actually reduce the viscosity of the pus,
may prove to be of value. (67)
Surgery
The unresolved fibrinopurulent or chronic empyema has always been the province
of the surgeon. Open thoracostomy with rib resection and Eloesser flap has
been the standard method of open and evacuating the cavity. Thoracotomy and
decortication with or without pulmonary resection has historically been reserved
for chronic empyemas where lung re-expansion is prevented by pleural fibrosis.
The development of video-assisted thoracoscopy (VATS) in the 1980s changed
that. (68) Now early exploration of the entire pleural cavity
under direct vision could be undertaken without the morbidity of a thoracotomy.
However, during this same period, the use of fibrinolysis and the proliferation
of imaging techniques, with the application of image guided drainage, have
in many cases delayed surgical referral with resulting negative consequences.
Avansino et al (69) using a meta-analysis of 23 years of
reports on empyema therapy in children has shown that primary operative therapy
compares favourably with non-operative therapy. The failure rate is significantly
reduced with primary operative therapy as are mortality rates, re-intervention
rates, hospital stay, duration of tube and antibiotics. Gates et al (70)
focusing on VATS reached similar conclusions. Other individual reports have
done the same.(71 - 73) Considering recent
doubts cast on the value of fibrinolysis, it is clear that all cases of stage
2 empyema which do not resolve promptly with tube thoracostomy or which have
thick, multiloculated fluid should have prompt surgical referral. The same
is true for all stage 3 empyemas. The Recommendations of the British Thoracic
Society BTS (disregarding the comments on fibrinolysis) would form a good
basis for therapeutic approach. (74) In light of this the
following recommendations can be made:
Open thoracostomy, rib resection and Eloesser flap
This historical approach to open surgical drainage is indicated when closed
drainage is unsuccessful, VATS is unavailable and adhesions have fixed the
lung to the overlying pleura. (75) A variable number of
ribs can be resected. It is particularly suitable when the patient is not
fit for general anaesthesia. BTS2.16 The cavity has historically been treated
with sterilizing solutions such as Dakin’s. Maruyama et al (76)
describes a slightly different approach.
VATS
Where facilities are available VATS is the procedure of choice for any empyema
not promptly (4-8 days) and completely responding to closed thoracostomy.
BTS2.15 General anaesthesia and double lumen endotracheal intubation are part
of this highly technical, but very effective, modality.(77)
Angelillo Mackinlay et al in 1996 favourably compared VATS with open thoracotomy
and recommended RCTs to define its role. (78) Sadly only
one RCT comparing immediate VATS with fibrinolysis has been published. VATS
was deemed to be more effective as a result of a significantly higher treatment
success rate, shorter hospital stay and duration of chest drainage. “Medical
thoracoscopy”, carried out under local anaesthesia and sedation, has
been described.(79)
Open thoracotomy with or without decortication
In settings where VATS is not available but where there is adequate surgical
expertise, open thoracotomy and drainage of abscess is indicated in stable
patients whose empyemas do not respond promptly (4-8 days) and adequately
to closed thoracostomy. (80) BTS2.15 Decortication is added
if a thick pleural peel prevents expansion of the lung. (81)
Lung resection may be necessary if there is a bronchopleural fistula or severely
damaged lung.
Thoracoplasty
In patients with chronic empyema, collapsed lung and pleural fibrosis who
are not fit for thoracotomy, a thoracoplasty can be done to collapse the chest
wall onto the lung thereby obliterating the cavity.
Pneumonectomy
Extra-pleural pneumonectomy can be carried for serious damaged lungs in the
presence of chronic empyema. (82) Most cases are associated
with chronic tuberculosis. This is an operation for experts.
Recommendations
1. All undiagnosed pleural effusions should be aspirated and have their protein
and LDH content measured and compared with serum levels. Exudates should have
cell counts and differentials, pH and glucose determination, gram and acid
fast staining and culture. Urine reagent sticks may be used in the absence
of formal chemical analysis.
2. Drainage is appropriate for all parapneumonic effusions which are greater
than ½ hemothorax OR loculated fluid OR culture or gram stain positive
OR pH<7.2. Other criteria such as frank pus, glucose<35mg/dL or LDH>1000IU/L
should also be considered.
3. Streptococcus pneumonia and staphylococcus aureus are the major pathogens
in childen; gram-negative aerobes and anaerobes predominate in adults.
4. Tuberculous pleurisy needs to be distinguished from TB empyema. The former
needs only ATB therapy, the later the full gamut of empyema strategies.
5. Chest tubes are important in traumatic pneumo- and hemothorax, but they
should be removed as soon as air and blood drainage cease. Risk of post-traumatic
empyema is a reflection of underlying lung injury.
6. Ultrasound examination should be undertaken in all pleural effusions and
especially those which do not resolve promptly with tube drainage. The presence
of septations is an indication of an increased risk of failure of tube drainage
and the need for surgical drainage.
7. Antibiotic protocols should be started before definitive culture reports
are available. These include amoxicillin/clavulinic acid or a second generation
cephalosporin such as cefuroxime plus an anaerobic agent like metronidazole.
In patients with penicillin allergy, a fluoroquinone like ciprofloxacin, a
carbapenem like imipenem, or perhaps chloramphenicol may be substituted.
8. Nutritional assessment and support should be offered to all empyema patients.
9. Empyemas should be classified as stage 1 – exudative; stage 2 - fibrinopurulent
and stage 3 - chronic.
10. Exudative empyemas (stage 1) which are less than ½ hemothorax,
are not loculated, with negative gram stain and culture and with pH>7.2
can be treated without drainage. These should be followed very closely with
xray and if necessary repeated thoracentesis to diagnose any progression to
stage 2 and ensure resolution.
11. In large or loculated stage 1 and all stage 2 empyemas the first line
therapy is prompt and adequate drainage, probably with closed tube thoracostomy.
Multiloculated collections have a higher risk of failure with tube drainage.
12. Failure of prompt (4-8 days) radiologic or clinical response after tube
drainage mandates surgical consultation.
13. In light of the MIST study, the role of intrapleural fibrinolysis in the
management of empyema is in doubt.
14. VATS, if available, is the procedure of choice for the evacuation of refractory
empyemas. VATS is probably one of the most useful minimally invasive procedures
in the African setting and is recognized in the FCS syllabus of COSECSA.
15. In the absence of VATS, thoracotomy, with or without decortication, is
indicated in multiloculated, inadequately drained empyemas.
16. All stage 3 empyemas require surgery as first line therapy. Thoracotomy
with decortication is required. Lung resection may be necessary in some cases,
particularly if there is a bronchopleural fistula. Some cases can be managed
by VATS.
17. Open thoracostomy with rib resection and Eloesser flaps should be used
in localized and inadequately drained empyemas, particularly when the patient’s
condition is poor or expertise lacking.
Dr. Brian Ostrow
Guelph, Ontario
Click here to join the Surgery in Africa Discussion Group