Clinical Management of Tuberculosis

Dato Dr Hj Abdul Razak Muttalif MBBS, MSc, M.Med, AM, FCCP Consultant Chest Physician & Head Department of Respiratory Medicine Hospital Pulau Pinang

Diagnosis of Tuberculosis

Pulmonary Tuberculosis
 Symptoms & Signs  Investigations

Sputum AFBs X 3, AFB C&S (egg based media, BACTEC)

 Chest X-rays  Mantoux test

Duration of symptoms from first visit
70 60 50 40 30 20 10 0 Days Weeks Months Years Percent

Razak,Norhafizah,Norlidar,Norhashimah. C.C.HKT

2.Microbiology
 

Sputum AFB/AFB C+S Most cost effective method Categorization for treatment
 

AFB +ve AFB -ve

3. Serology
 Mantoux Test  Antibody/antigen  PCR

More than 10mm is positive

2TU in 0.1 ml, read after 72 hours

In children more than 15 mm

4.CXR
 Upper lobe opacity  Cavity ( 1 cavity= 1 million bacilli)  Miliary  Effusion

Radiological classification
 Minimal

Slight lesion without cavitations, confined to a small part of one or both lungs. Total extent of lesions should not exceed the volume of lung which lies above the second chostosternal junction and the spine of the fourth vertebra

Radiological classification
 Moderately advanced

One or both lungs may be involved. Total extent of lesion should not exceed the following:

i) Not exceeding total volume of one lung  ii)Dense lesions not exceeding one third lung volume  Iii)Total diameter of cavity less than 4cm

Radiological classification
 Far advanced

Lesions more extensive than moderately advanced

Extra pulmonary TB (TB outside the lung
parenchyma)
     

Tuberculous lymphadenitis by LN biopsy sent for DS, C&S, cytology TB effusion by pleurocentesis, pleural biopsy GUT by radiological, urine C&S TB bones/joints by x-rays, HPE Miliary TB by CXR,liver biopsy TB meningitis CSF microscopy, biochemestry C&S, PCR for TB

Tuberculosis Classification
 Pulmonary tuberculosis
 

Smear positive Smear negative

 Extrapulmonary tuberculosis  Pulmonary with Extrapulmonary

tuberculosis

Pulmonary Tuberculosis
 Smear positive
  

Two sputum DS positive One sputum positive with CXR changes of TB One sputum positive with culture positive Three DS negative with CXR abnormalities and decision to treat as TB Initial sputum DS negative but culture positive

 Smear negative

Extra Pulmonary TB
 Extra-pulmonary TB
 

TB of organs other than lung parenchyma Based on culture, histology or strong clinical evidence and a decision to treat Tuberculosis involving lung parenchyma as well as any other part of the body

 Pulmonary with extra-pulmonary

Extrapulmonary TB classification of severity
 Severe

Meningitis, miliary, pericarditis, peritonitis, bilateral or extensive pleural effusion, spinal, intestinal, genito-urinary Lymph node, unilateral pleural effusion, bone (excluding spine), peripheral joint, skin

 Less severe

Definition of terms
 New case  Relapse case  Chronic case  Cure  Treatment failure  Treatment after interruption  Transferred in case

Definition
 New case  Newer had TB treatment or has take treatment for less than 4 weeks in the past  Relapse case

Sputum positive relapse  Declared cured of any form of TB in the past by a doctor has become sputum smear positive Sputum negative relapse  As above, developed active disease based on bacteriological, histological clinical and radiological assessment

Definition
 Chronic case

A patient who remained or becomes smear positive again after completing a fully supervised re-treatment regimen A smear positive patient has negative sputum at the end of treatment and another negative sputum one month or more prior to completion of treatment

 Cure

Definition
 Treatment failure  A patient while on treatment becomes again smear positive 5 months or later after commencing treatment  A patient who was initially negative became positive after second month of treatment  Treatment after interruption

A patient who interrupts treatment for 2 months or more then returns with smear positive or negative but still active TB based on clinical or radiological assessment

Definition
 Transferred in case

A patient transferred from another centre for continuation of treatment. The new centre undertakes the responsibility of treatment Not considered a transfer if a patient just come to centre for treatment only

Tuberculosis in children
 Infection from adults via coughing and

droplets  From milk and food  Through skin

Changes after infection in children
 Primary complex  Pleural effusion  Acute cavitation of focus  Ring shadow  Lymph node at root of lung  Blood spread

Liver, bones, brain kidneys

?TB in children
 Failed to gain weight  Wheezing, cough, fever, LOA, LOW  Pleural effusion  Ascites  Joint swelling, spinal lump  Lymph node, discharging sinus  Headache, irritability

FAMILY HISTORY OF TB!!!!

“Two Diseases - one Patient”

Tuberculosis
T helper lymphocytes
Protective Immunity

Immunopathology Stress Glucocorticoids
Th1

and disease

Th1

+

Th2

Tissue damage
Macrophage activation

The immune response

Altered cytokines in HIV/TB patients
Normal CD4 INF IL-12 IL-10 TNF 231 759 7.5 0.6 Tb 569 10 12.5 424 370 TB/HIV 201 2.2 4 735 232 21 Advanced HIV 130 0.1 2.2

TH1 cytokines---IL-12,INF Inhibitory cytokines IL-10

S.swaminathan et al 2002

Effect of TB on HIV
 TB causes release of TNF and

stimulates multiplication of virus inside T cells  TB helps in destruction of CD4 cells  Helps release of new virions from HIV infected cells

Effect of HIV on TB
 Decrease macrophage activating

lymphokines  Increase in number of CD8 cells  Increase tissue destruction  T4 lymphopenia  HIV promotes T4 destruction and CD4 cells impairment

Effect of HIV on TB

HIV Status Negative Positive

Lifetime risk of developing TB 5-10% 50%

Chest Imaging (in HIV +ve case)
 Not used for screening  Limited to symptomatic  Variety of manifestations  Normal CXR in 15%,CT scan used only

for further diagnostic procedures  Gallium scan for PCP

CXR findings in HIV patients (1)
 Normal

PCP, MTB, Histoplasma, Kaposi PCP, MTB, bacterial, Cryptococcus,aspergillus PCP, MTB, bacterial Cryptococcus, histoplasma

 Focal infiltrates

 Diffuse infiltrates

CXR finding (2)
 Nodular  PCP, Cryptococcus, Histoplasma, Norcardia, CMV, Toxo  Cavitary

Bacterial, PCP, MTB, Aspergilluss

 Lymphadenopathy  PCP, MTB, Cryptococcus, Kaposi, lymphoma  Pleural effussion

Bacterial, PCP, MTB, lymphoma

 Pneumothorax  PCP, MTB

Pneumococcal

Staphylococcal

Lung abscess

Acceleration of TB in HIV patients
Among 30 residents from a housing facility for HIV infected persons, 11 patients had active TB and were noted to have the same restricted fragment length polymorphisms (RFLPs) 4 others had positive TST 6 of the 28 staff members had positive TST Conclusion: Newly acquired TB infection in HIV infected patients can spread readily and progress rapidly to active disease. Heightened surveillance for TB in facilities as this is needed
Charles et al. NEJM 1992;326:231-5

PTB mini epidemic in a church Gospel Choir
 Five cases of TB, one index and three

secondary  All three had same DNA fingerprinting  All three were tenors (not sopranos)  Singing, location of ventilation and exposure time were contributing factors

Bonita et al Chest 1998; 113: 234-37

PTB in early and late HIV infection

Features of PTB

Stage of HIV infection
Early Late
Often resembles primary PTB Often negative Often infiltrates with no cavities

Clinical picture Sputum smear CXR

Often resembles post primary PTB Often positive Often cavities

CD4 count and CXR
 35 subjects, 26 had CD4 <200cells/L  21 of these subjects had atypical CXR  Atypical CXR
    

Diffuse lower lobar opacities Pleural effusion Mediastinal lymphadenopathy Interstitial nodes Normal x-ray
Kelper et al. Chest;107:74-80

CXR in HIV patients
 225 Haitians tested for HIV  67 positive and 158 negative  Intrathoracic adenopathy more common then

parenchymal infiltrates (p<0.05)  80% of patients with AIDS has CXR consistent with primary TB (p<0.05)

R Long et al Chest; 99: 123-127

Pulmonary nodules in HIV patients*
Diagnosis
Bacterial PCP Lymphoma Tuberculosis Kaposi NTM Aspergillus Lung Ca CMV

Number
88 26 25 23 16 15 9 4 2

* 242 HIV patients who had CT chest

Robert et al Chest 2000; 117:1023-1030

CD4 count and lung nodule
CD4 cell count Diagnosis Pneumonia TB PCP Aspergillus Kaposi 0-49 17 4 2 3 9 50-99 1 5 0 0 1 100-199 >200 8 4 0 0 1 4 1 1 0 0

87 HIV patients with lung nodules

Robert et al Chest 2000; 117:1023-1030

Undiagnosed TB in patients with HIV infection (Dept of Med, U of Souther Califonia Medical
Center) Flora et al

 11 patients with HIV TB undiagnosed  9/11 had pulmonary complaints  8/11 had x-ray suggestive of TB  Non of these patients had TST  AFBs in only 3 patients and bronchoscopy in

only 4  PCP was the main presumptive diagnosis  Three had post mortem diagnosis of TB and 7 had evidence of disseminated TB

Chest 1990 Vol 98 1056-1059

Significance of abnormal CXR findings in patients with HIV infection and respiratory symptoms
 44 patients were eligible  86% had CD4 count <200cells/uL  Nodular disease was commonest (57%)  Adenopathy (17%)  Most common diagnosis was TB followed by

NTM  Only 18% with TB had diagnosis by sputum

Jeffrey A Gold et al. Chest 2002;121:1472-1477

Other Investigations

Variables
Nodules Adenopathy Infiltrate Cavity Mass Effusion

CXR
22 7 5 4 4 2

27% 38%

11% 3% 5% 8% 8%

Scope TTNA Surgery Thoracentesis FNA Clinical Sputum

Diagnosis Infectious Neoplasia Lymphoproliferative Others Unknown

Percent 52 (MTB 26, NTM 23) 19 (KS 12, NSSCa 2, HL 2 ) 7 7 14

Bronchoscopy

Treatment of Tuberculosis

Aims of treatment
 To reduce morbidity  To prevent mortality  To prevent relapse of tuberculosis  To decrease transmission  To prevent the emergence of MDR TB

Treatment of TB
 Responsibility is to the public health, not

patient  Patient centered  Each patient management plan should be individualised  DOTS

First line drugs
 Isoniazid (H)  Rifampicin ( R )  Pyrazinamide (Z)  Streptomycin (S)  Ethambutol (E)

Treatment categories

Category I New case

Category II

Category III

Relapse Treatment failure

Chronic case

Sputum positive, MO boleh treat

Treatment after interruptio n

Refer to physician/che st

Treatment regimens
 Intensive or initial phase

Three or four drugs given daily for rapid sputum conversion and amelioration of clinical symptoms Two or three drugs given intermittently for sterilizing effect and to eliminate remaining bacilli and reduce chance of relapse

 Maintenance or continuation phase

Category I (New case)
 Intensive phase

2SHRZ or 2EHRZ or 2HRZ two months of daily doses 4H2R2 or 4S2H2R2 or 4HR or 4H3R3 or 4S3H3R3 durations extended for severe form of TB or extrapulmonary TB

 Continuation phase

Category II (Relapse, Treatment failure,
Treatment after interruption)

 Send MTB C&S (rapid culture if

available)  Do not initiate standard treatment  Refer to chest physician or physician in charge of chest clinic  Subsequent drug regimen based on sensitivity results and clinical response

Category III (Chronic case)
 Send MTB C&S (Rapid culture if

available)  Refer to chest physician or physician in charge of chest clinic

Anti TB drugs
Daily dosage mg/kg Isoniazid H Rifampicin R Streptomycin S Ethambutol E Pyrazinamide Z 5-8 10-15 15-20 15-25 20-40 max 300 600 1000 1200 1500 Biweekly dosage mg/kg 15-20 15-20 15-20 50 50 max 1200 600 1000 2000 3000

Multi- drugs(first line)
Intracellular RIF INH PZA SMC Extracellular Cavity

+ + + _

+ + _ +

+ _ _ _

Flow Chart for 6 months regimen
1. 0 mo (0 w) 2SHRZ/2EHR Z Baseline Ix:FBC,LFT,RP,HIV,R BSSpt AFBs DS, AFB culture Spt AFB DS, spt culture if smear positive,CXR

2. 2 mo (8w) 3. 2 mo (8w)

4SHR2
Continue Rx

4HR2

Continue RxSpt AFB DS, CXR

4. 2m (8w)

Completion of 6 mo Rx

Spt AFB DS, CXR

5. 6mo(24w)

Follow up

Spt AFB, CXR

Practical Aspects
 All anti TB drugs given together, do not

split dosing  Vigilant for drug interactions  Empty stomach? After food?  AntiTB drugs should not be stopped or minor side effects especially RIF

NOTIFICATION!!! !!

Patient Monitoring
 Treatment response

All patients with positive sputum have repeat sputum smears every two months

 Patient compliance by DOTS  Hospitalisation

Gravely ill, acute disseminated TB,TB of vital organs,MDRTB,frequent defaulters,complications, severe side effects, homelessness

Contact tracing!!!
 Family members  Workplace  Close contacts  Inmates  Institution

Drug toxicity monitoring and management

Monitoring for drug toxicity
 All patients should have baseline Ix  Monitored clinically for adverse reaction  Routine blood Ix for asymptomatic

patients not required  If symptoms suggesting drug toxicity, perform appropriate Ix

Drug Toxicity
 Minor side effects  GI intolerance  Arthralgia  Mild rash  Serious side effects
     

Hepatitis Severe skin rash Thrombocytopenia Shock Renal failure, eight cranial nerve damage Visual impairement

Drug interactions
 Isoniazid
 

Raises the level of phenytoin,carbamazepine Absorption of INH impaired by allumonium hydroxide Need to increase dosages of PIs,steroids, OCP,OHA, anti-coagulants, phenytoin, cimetidine, theophylline and digitalis

 Rifampicin

Outcome analysis
 Cure  Smear negative on two occasions at completion of treatment  Treatment completed  Completed treatment without proof of cure  Treatment failure  Remains positive of becomes positive again at five months of treatment  Died  Dies for any reason during course of treatment  Treatment interrupted  Treatment interrupted for two months or more

TB in Children
 Diagnosis is difficult  Features:

Recent contact, symptoms and signs, unresolving pneumonia, positive mantoux, hilar nodes, segmental collapse, pleural effusion, LN calcification

 Gastric lavage for DS and culture  Bronchoscopy if necessary

Anti-TB in children
 Intensive phase

HRZ for 2 months (syrup preparation) Daily RH is preferred Biweekly RH fully supervised

 Maintenance phase
 

 Avoid ethambutol and streptomycin

TB meningitis
 Total duration is 12 months  Steroids in acute stage  Observe for late complications like

hydrocephalus

TB in pregnancy and lactation
 Standard treatment and dosage  Avoid streptomycin  Breast feeding best avoided for 2 weeks

in a mother who is a new smear positive case  BCG and INH prophylaxis given if needed

TB and OCP
 Rifampicin interacts with OCP  Decreases protective efficacy against

pregnancy  Use a higher dose of oestrogen or other form of contraception

TB and liver impairment
 Established chronic liver disease
  

i) 2SHRE/7H2R2 ii) 2SHE/10HE Iii)2SH/12S2H2 Hepatitis unrelated to TB or TB treatment, defer treatment until hepatitis is resolved if treatment is necessary, 3SE/6HR

 Acute hepatitis (viral hepatitis)

TB and renal impairment
 Streptomycin and ethambutol avoided  If need to be given, monitor renal function

closely  2HRZ/6HR is safest regimen

TB and HIV
 Initial therapy

INH, RFP, PZA , ETM IHN and RFP for 7 months biweekly or for 6 months after culture is negative

 Long term

Antiretroviral Drugs
 Nucleoside reverse transcriptase inhibitors (NRTI)
   

Zidovudine (AZT) Didanosine (ddI) Zalcitabine (ddC) Stavudine (d4T) Efavirenz (Stocrin) Nevirapine (Viramune) Indinavir Ritonavir Saquinavir

 Non-nucleoside reverse transcriptase inhibitors (NNRTI)
 

 Protease Inhibitors (PI)
  

Managing HIV/TB co-infection
 HAART decreased death by 60-90%  In absence of HAART higher mortality

due to OIs  HAART /anti-TB has overlapping toxicity, drug interaction, non-adherence, paradoxical reactions  Recommended to delay HAART until first two months of TB treatment

Anti TB and HAART
 PIs and NNRTIs inhibit or induce

cytochrome P450 (CYP450)  Rifampicin induce CYP450 and decrease levels of anti-retrovirals  NRTIs (AZT,ddI,ddC,d4T,3TC) are not metabolised by CYP450  Concurrent use of NRTIs and rifampicin is not contraindicated and does not require dose adjustment

TB treatment in HIV patient
 In patients with no HIV treatment, usual

regimen  In patients with HIV treatment, omit rifampicin and rifabutin or add streptomycin

Two options for TB Rx
 INH + RBT + PZA +  INH + PZA + ETH +

ETH for two months then  INH + RBT for 4 months  Do not use ritonavir, delavirdine, dose of PI adjusted
RBT=rifabutin

SM for 2 months then  INH + PZA + SM for 7 months  PIs can be used at usual dose

New options
 Rifampicin can be used in 3 situations:
  

I) NNRTI (efavirenz) + 2 NRTIs II) Ritonavir + one or two NRTIs III)Use of two Pis (ritonavir + saquinavir)

 Use of non rifampicin included regimen

with longer duration

Pharmacologic interactions between rifampicin and efavirenz Coltres et al
24 HIV positive patients randomised into 3 groups: 1. Rifater + E(600mg qd) + 2NRTIs (D8-D14) 2. Rifater + E(800mg qd) + 2NRTIs (D8-D14) 3. Rifater + E(800mg qd) + 2NRTIs (D1-D14)

Result: 30% decrease in E level in group 1. No change in rifampicin levels Conclusion: Rifampicin and efavirenz can be used concomittently with a higher dose of efavirenz. Advise use of FDCs

8th Conference in Retroviruses and OIs February 2001, Chicago

Paradoxical worsening of TB in HIV infected persons (Johns Hopkins)
 HAART results in partial restoration of

cell mediated immunity  36% of patients who receive anti-TB and HAART compared to TB treatment alone  Low CD4 counts higher risk  Occurred 4-10 weeks after initiating treatment  Increased risk of TB relapse
Karen A Wendel et al. Chest 2001;120:193-197

Drug malabsorption and resistant TB in HIV patients (Kalpana Patel, Hartford Hospital)
Drug INH RIF PZA ETH Cipro Optimum Level 3-5 8-24 20-60 2-6 4-6 Patient One 0.80 0 24.9 0.40 0.47 Patient Two 0.92 0 34.81 0.86 1.3

Serum levels measured after 2 hours of oral administration in ug/ml

Drug malabsorption may contribute to MDRTB

Fixed Dose Combinations (FDC)
 Rifinah/Rimactazid/Rifamate (RFP and

INH)  Rifater (RFP, INH and PZA)  Myrin (ETM, RFP and INH)  Myrin P (ETM, RFP, INH and PZA)

FDC
 Advantages
   

Decreases MDRTB An effective regimen No medication errors Patient compliance Bioavailability, use only FDC approved Cost Dosage adjustment

 Disadvantages
  

DOTS

Directly Observed Treatment, Short-course (DOTS)
 Government commitment to a NTCP  Case detection by sputum microscopy  A standardised short course treatment

under direct observation  A regular uninterrupted supply of quality anti TB drugs  A monitoring and reporting system to evaluate treatment outcome

Advantages of DOTS
 Cure rates of up to 95%  Integrated with primary health care  Microscopy is cheap and reliable  Trained health care workers or community volunteers    

can supervise No hospitalisation or isolation Prevents MDRTB Reording system ensures cure Cost effective

Combined chemotherapy strategy in TB control
DOTS
No specific chemotherapy

T B

Drug susceptible TB Specific chemotherapy

Time

Defaulter tracing and retrieval
 Defaulter

Missed 25% of treatment doses in one month

 Retrieve by phone call, letter on same

day  Home visit if not turn up by 3rd day

Prevention of TB among Health Care Workers (HCW)
 Transmission of TB to HCWs depends

on:
    

Number of patients with active TB The infectiousness of the index case The ventilation rate of the worker The duration of exposure The air-exchange rate in the interior space

TB and HCW
 Administrative controls

Developing and implementing effective protocols for rapid identification, isolation and treatment Effective work practices by education, training and counseling Prevent spread and reduce concentration of infectious droplet nuclei (exhaust fan, unidirectional flow, ultraviolet germicidal irradiation, biological safety cabinets classII)

 Engineering control

 Personal respirator protection

Surveillance of HCWs for TB
 All HCW have CXY on employment  Those working in high risk area, have

CXR every two years  Workers with symptoms should be evaluated for TB  Infected HCW given long leave

Latent TB Infection (LTBI)
 2 billion people worldwide have LTBI  Most cases of active TB arise from LTBI  Improved diagnosis and treatment of

LTBI is a major route of preventing and decreasing incidence and mortality from TB  Direct TST to population at risk  Offer simple short course regimens (2 months of RIF and PZA)
6th Annual IUATLD Conference Chicago 2001

Drugs for preventing TB in HIV infected persons
 Seven trials were reviewed  Preventive therapy compared with placebo  Lower incidence of active TB (46%) in preventive group  Incidence of TB reduced in people with positive TST

compared with negative TST  Death were less frequent in those with positive TST and taking preventive medicine  Any regimen (INH alone, INH +RIF or INH + RIF+PZA) has similar protective effects  Preventive therapy is effective in reducing death and active TB in positive TST group

Wilkinson D, Cochrane Review Abstracts

Targeting persistence
 One third of worlds population infected

(1.8 billion)  8 million with the latent disease develop reactivation  30% only fully treated in the world  5-20% reactivate after treatment  Stanford researchers identified genes involved in latency

Persistence and latency
 48 genes involved  Ability of bacteria to respond to low

oxygen levels and increased nitric oxide  The genes transform the physiological state, biochemical pathways and structure of organism  Drug strategy for latency

Surgery in Tuberculosis

Surgery in Tuberculosis
 Pneumothorax  Empyema  MDRTB

Pneumothorax
Treatment  Observation & bed rest  Aspiration  Chest tube drainage  Pleurodesis  Surgery

Pneumothorax Treatment Observation
Small (<20%), asymtomatic, good health Rate of air resorption = 1.25% or 50-70ml/day O’Rourke and Yee Chest 96:1302 1989 - 5% (2/40) mortality - tension pneumothorax - 22.5% - subsequent chest drain Prolonged observation (>14 days) Entrapped lung with chronic pneumothorax
-

Chest tube or aspiration if not re-expanded after one week

Pneumothorax Treatment Aspiration
 Success rate = 50%  Recurrence rate = 20-50%

Pneumothorax Treatment Tube Thoracostomy
 Moderate – large pneumothorax  Rapid re-expansion of the lung  Air leak usually stops within 48 hours  Allow chemical pleurodesis to be

performed. Eg talc, tetracycline, bleomycin

Pneumothorax Treatment Recurrence
 Observation

30%  Aspiration 20-50%  Chest tube drainage 20-30%  Pleurodesis (tetracycline) 25%  Pleurodesis (talc) 7%
 Surgery

2%

Pneumothorax Indications for Surgery
First episode  Tension pneumothorax  Bilateral pneumothoraces  Haemo-pneumothorax <5%
 Non re-expansion of the lung  Prolonged air leak (>3-4 days) – 3-5%  Occupational hazard (flight personnel, divers, frequent flyers)  Associated single large bullae  Live in isolated remote area with no medical facilities

Second episode  Ipsi-lateral recurrence  Contra-lateral recurrence

Pneumothorax Treatment Surgical Approach
Thoracotomy  Conventional  Limited muscle sparing VATS (Video assisted thoracoscopic surgery)  Three small incisions  Allow bilateral procedures

EMPYEMA THORACIS Indication for Surgery

Empyema Thoracis
Paget 1896  “….unhealed empyema is, as a rule, the direct result of patient’s neglect, or of the surgeon’s delay, or of inadequate and useless surgery. ”

Empyema Thoracis
Sir William Osler 1892 “ It is sad to think of the number lives which are sacrificed annually by the failure to recognize that empyema should be treated as an ordinary abscess by free incision” Open drainage with rib resetion recommended

Empyema Thoracis
Evarts Graham – Am J Med Sci 1918 Open drainage – 30% mortality

Empyema Thoracis
The Empyema Commission – Evarts Graham 1925
 Recommended closed tube drainage

5-10% mortality

American Thoracic Society Pathological Stages
Acute 1: Exudative, pleural swelling 2: Fibrinopurulent, with heavy fibrin deposits Chronic 3: Organization with in growth of fibroblasts and deposition of collagen (4-6 weeks)

Empyema Thoracis
Complications
 Pulmonary fibrosis and contraction of chest wall  Spontaneous Drainage

1. empyema necessitatis 2. brochopleural fistula 3. osteomyelitis 4. pericarditis 5. mediastinal abscess

Management Acute Empyema
 Nutrition, physiotherapy, underlying

medical condition
 Anti TB treatment is vital  Drainage

Management Acute Empyema
Drainage – cornerstone 1. evacuation of pus 2. apposition of pleural surfaces and obliteration of pleural space Must be performed as early as possible

Acute Empyema Pleural Drainage
Conservative 1. Closed tube drainage 2. Intra-pleural fibrinolytics (streptokinase or urokinase) Surgical 1. Video assisted thoracoscopy 2. Thoracotomy – limited, muscle sparing, full Refer early

Acute Empyema Pleural Drainage

Minimum size 32F recommended  Works best before formation of loculi Principle All infected fluid and pus must be drained

Empyema Thoracis Indications for Surgery
 Evidence of significant residual effusion on CXR    

despite chest drain insertion Non-reexpansion of the lung after evacuation of empyema Multiple loculated collections demonstrated on ulrasound or CT Chronic empyema with trapped lung Complications

Empyema Thoracis Pleural Drainage
CT or ultrasound guided pigtail catheter drainage in multi-loculated pleural empyema: a recommended procedure?.
Maier A Respirology. 5(2):119-24, 2000 Jun.

RESULTS:  Image-guided drainage failed in all (14/14) patients.  Septic symptoms disappeared within 24-48 h after surgery with decortication.

Empyema Thoracis Intrapleural fibrinolytics
38-100% Success in Resolution of empyema  69% (18/26) of patients. Temes RT. Chest. 110(1):102-6, 1996 Jul.  77% (10/13 patients) Robinson Ann Thor Surg 1994;57:803
Cochrane Database of Systematic Reviews [computer file]. (3):CD002312, 2000

- Results not consistent across studies to recommend routine use

Empyema Thoracis Intrapleural fibrinolytics
 Controlled trial of intrapleural streptokinase in the treatment of pleural

empyema and complicated parapneumonic effusions.
Chin NK. Lim TK. Chest. 111(2):275-9, 1997 Feb.

 RESULTS: The incidence of surgical decortication was 17% and mortality

was 15%.

 There were no significant differences between the two treatment groups in

terms of the need for surgical intervention, or mortality rates.
Twenty-nine patients were treated with Drain only 23 received, in addition, repeated daily SK, 250,000 U in saline solution (mean, 5.3 days).

 

Empyema Thoracis Operative Drainage
 Mortality rate

drain alone 24%

vs SK+ early OP = 3%

 The average duration of hospital stay in the SK+early OP

group was significantly shorter than in the Drain and IPSK groups.

Lim TK. Chin NK. National University Hospital, Singapore Empirical treatment with fibrinolysis and early surgery reduces the duration of hospitalization in pleural sepsis.  European Respiratory Journal. 13(3):514-8, 1999 Mar.
  

1) Drain (n=29, chest catheter drainage); 2) IP-SK (n=23, adjunctive intrapleural fibrinolysis with 250,000 U x day(-1) SK) 3) SK+early OP (n=30, early surgical drainage was offered to patients who failed to respond promptly following initial drainage plus SK).

Empyema Thoracis Video Assisted Thoracoscopy VATS
 Fibrino-purulent stage with loculated collections

Success rate  71% (48/67)
Striffeler H. Gugger M. Annals of Thoracic Surgery. 65(2):319-23, 1998 Feb.

 68% (30/44)
Lawrence DR. Ohri SK Annals of Thoracic Surgery. 64(5):1448-50, 1997 Nov.

 28% (2/7) children
Steinbrecher HA. Najmaldin AS.Journal of Pediatric Surgery. 33(5):708-10, 1998 May

Chronic Empyema Options
1. Thoracotomy and decortication 2. Rib resection & open drainage 3. Space sterilization 4. Muscle or omentum transposition 5. Thoracoplasty 6. Total pleuro-pneumonectomy

Empyema Thoracis Thoracotomy
 Significant complications in children who had

delayed thoracotomy.  Early thoracotomy hasten patient recovery regardless of the stage of disease.

Recommend aggressive early operative approach to empyema thoracis
Shankar KR. Acta Paediatrica. 89(4):417-20, 2000 Apr Renner H. Gabor S. European Journal of Cardio-Thoracic Surgery. 14(2):117-22, 1998 Aug.

.

Empyema Thoracis Conclusions (1)
 Acute empyema is easily treated  Chronic empyema has high morbidity

and mortality Chronic empyema is avoidable

Empyema Thoracis Conclusions (2)
 Early chest drain insertion  Early surgical referral

Aggressive = Quick Recovery Conservative x8 mortality
Lim TK. Chin NK. European Respiratory Journal. 13(3):514-8, 1999 Mar.

Empyema Thoracis
“Early recognition of complicated empyema and institution of surgical interventions as primary therapy rather than as a last resort will likely result in improved survival and shortened hospital stay”
Ferguson MK: The Healing Hand. Chest 97:4, 1990

Chest Drain

Chest Drain Closed Water seal System
 Gotthard Bülau 1891 –Hamburg,

Germany

Indications for Chest Tube
 Pneumothorax  Haemothorax  Empyema  Pleural effusion  Chylothorax  Post-op – Thoracic & cardiac

Chest Tubes
 6Fr (paediatric) to 40Fr  Pure pneumothorax – minimum 24Fr  Haemothorax, effusion and empyema –

minimum 28Fr recommended
 Drains with multiple side holes preferred

Insertion site
 3rd to 5th intercostal space in the anterior axillary    

or mid-axillary line behind the pectoralis muscle Advantages No muscles other the intercostals Scars less visible More comfortable

 Avoid the front (muscles and breast) and the

back ( painful)

Insertion technique
 Aseptic technique  Local anesthesia with lignocaine 3mg/kg

from skin down to pleura  Aspirate air or fluid to confirm location

Insertion technique
 2cm incision just above the rib  Blunt dissection with artery forceps over

the superior border of the rib into the pleural space  Finger palpation to confirm entry into the pleural space; absence of adhesions and loculated space  Introduce the drain to apex or basal space

 Anchor the drain with a simple skin stitch

( number 1 or 0 size)  Another simple stitch for later skin closure after removal of drain  Confirm the drain is swining well / bubbling or draining
 CXR to check position / lung re-

expansion / drainage

Insertion technique
 Should be painless if done properly (infiltrate

lignocaine widely and the right space)
 Avoid trocar ( can puncture lung, heart, spleen,

liver, oesophagus, aorta and diaphragm)
 Avoid purse-string ( ugly puckered scar)  Simple dressing

Tube Management
Monitoring  Early and daily CXR  Air leak and fluid drainage
 Maintain tube patency (swinging)  Ensure air–tightness of closed system

Tube Removal
 Complete lung re-expansion >48 hours  No air –leak  Drainage <100ml / 24 hour  Clamping of tube not necessary, probably in

cases with intermittent air leak

 Removed at and inspiration or when

peforminga Valsava maneuver  Check CXR

One way Drainage System

One way Drainage System
Advantages  Cheap  Simple Problems  Higher resistance with fluid accumulation  Foaming

Suction Device

Indications for Suction
 Failure of lung to re-expand with good

size patent chest drain  To promote drainage of blood and fluid Contra-indications  Massive bleeding  Pneumonectomy