Management of Critically Ill

Patients with Tuberculosis

in ICU : From Diagnostic to
Infection Control
dr. Dwi Hartanto,SpP,FISR
 Contents
1. Introduction
2. Clinical Presentation in ICU
3. Management of Patients in ICU
• 3.1 Organ - Specific TB – management and support
• a. Pulmonary TB
• b. Central Nervous System TB
• c. Pericarditis TB
• d. Abdominal TB
• e. Further Extra Pulmonary TB Manifestation
• f. Disseminated TB
• 3.2 Anti TB Drugs and Treatment Regiment
• 3.3 The Use of Steroids
• 3.4 Management of HIV-Co-Infected Patient
• 3.5 Infection Control and Preventing Spread of Infection
• 4. Conclusions.
 Introduction
• WHO 2016 : 10.4 million new TB cases. 10% (1 million) + HIV
• 60% of new TB cases from 6 endemic area ( India, Pakistan,
Indonesia, China, Nigeria and South Africa)
• 2016 estimated 490.000 cases MDR
• TB disease struggle or multiplied organ
• Comorbid
• Sub-clinical disease manifest/reactif during intensive Care unit
Clinical Presentation in ICU
• Early TB deaths Acute Cardiorespiratory Failure
• Comorbidity with HIV and other Communicable disease Highly
prevalent
• Acute Respiratory Failure, septic shock, MODS
most reason for ICU admission
• Common causes of critical …. And patient with active TB :
- Bacterial co Infection
- Anti TB drug toxicity
- Tromboembolic complication
Management of Patient in ICU :
Pulmonary TB
• The most commonly affected organ in TB
• Acut Respiratory Failure with pulmonary TB Relatively Low (1,5-5%)
• Co - HIV Infection / Extensive ( miliary) / Advanced infection
cause of critical illness
• Mycobacterium induced injury of the alveolar capillary membrane
increased extra vascular lung water ,induced a ventilation perfusion
mismatch and increase the alveolar artrial gradient
• Interstitial granulomatous infections and obliterative
endarteritis…contributory factors in the patohysiology of ARF due to
pulmonary TB ..clinically as ARDS..in advanced disease, air spaces become
destroyed by caseating granulomas and fibrocavity lesion.
• The mortality of patients TB – associated ARDS exceeds that of patients
with ARDS from any other cause. ( admission during anti-TB treatment )
• The failure rate of non- invasive ventilation in patients with TB-
associated ARDS is High, Invassive ventilation do not differ from other
patients with ARDS…need for mechanical vent support often prolonged.
• Complications : Bacterial infection, pulmonary haemorrhage, pleural
effusion/empyema and or pneumothorax... Px with underlying
Immunosuppresion and prolong mec ventilation…Nosocomial bacterial
inf…VAP etc.
• Management of complications …appropiate with type of complications
Central Nervous System TB
• TB –associated pathologies of the CNS : delirium,TBM, tuberculoma of
the brain or spinal cord and stroke
• Complicates military TB ( in children ) and HIV – positive subjects.
• Mortality rate 67 % in HIV- positif patients
• Approximately half of survivors suffer from neurological sequele
• Pathophysiology : haematogeneous spread of TB bacilli.
• Symptoms : fever, headache, loss of appetite,malaise, vomiting..sub
acute onset. Agitation, cranial nerve palsies.
• Diagnosis : Fundoscopy ( papillordema, neovascularization) and lumbar
puncture. CT scan, MRI. Cerebrospinal fluid analysis, smear microscopy
stain Ziehl Neelsen
• Patients withTBM requiring ICU ( agitation and decreasing level of consciousness.
• 75 % of critically ill patients required intubation and mechanical ventilation.
• WHO guidelines recommend timely initiation of anti TB treatment with first line
drugs, although new data suggest a promising role of fluoroquinolones.
• Steroid therapy with dexamethasone or equivalent doses of prednisolone is
recommended..duration steroid tx 2 months with weaning of the steroid dose over
this period.
• Neuro surgical : indicated for evacuation of large a tuberculoma.
• General neuro intensive care : regarding temperature control, cardiorespiratory
management and blood sugar control.
• Complication : hydrocephalus,seizures, sodium disturbaces and stroke
Pericarditis TB
• Pericarditis TB and Pericardial effusion : haematogenous spread of a
lung lesion or rupture of a caseous lymph node into pericardium.
• Diagnosis : clinical symptoms, ecg and pericardial puncture.
• Tx : OAT, steroid ( prednisolone 60 mg / d for 4 week followed by 30
mg/d for 4 weeks and then 15 mg/d for2 week and 5 mg/d for 1 weeks
• Large pericardial effusions with or without tamponade …percutaneous
puncture and or surgical drainage.
Abdominal TB
• Abdominal TB complicates one third of cases with pulmonary TB.
• Mainly includes gastrointestinal TB and peritonitis TB
• 75 % cases.. Results from ingestion of infected sputum in acute pulmonary TB and
involves the terminal ileum and ileocaecal.
• Haematogeneous seeding and direct spread from infected lymph node are the
pathogenetic mechanisms leading to peritonitis TB
• Clinical symptoms..depend on the underlying pathology, 30% acute abdomen, 75 %
abdominal pain, 60 % ascites, 50 % weight loss.
• Diagnosis : CT Scan, ascitic puncture, laparoscopy or blind peritoneal biopsy
• Tx : anti TB drugs and supportive, surgery for px with perforation, complete
obstruction or massive bleeding.
Further extrapulmonary TB manifestations
• Haematogeneous seeding involve essentially all bodies tissues
and organs such as the liver, spleen, kidneys including urinary
tract ( potential to cause uretral strictures and hydronephrosis).
• TB laryng resulting in hoarsenes, cough and severe cases pain
and airway obstruction
• Bones and joints, the lower thoracic spine is affected most
frequently
• Tuberculous uveitis can cause blindness
• Conjunctivitis and erythema nodusum represent
hypersensitivity reaction to bacilli antigens in px with acute TB
Disseminated TB
• Miliary TB due to characteristic miliary pattern seen on chest X-ray
• Associated with mycobacteriaemia and multiple organ involvement (
lung, liver, spleen,meninges and kidney )
• Many patients present with ARDS and shock
• Disseminated intravascular coagulation and multiple organ
dysfunction are common.
• The Mortality of disseminated TB is High
Anti TB drugs and treatment regimens
• Anti- TB drugs are mainsty of TB treatment
• 2 months Intensive and 4 month a continuation phase
• Infection MDR and XDR.. Strains of M tb carries an exceptionally high
mortality and is growing challenge in many part of the world
• The tratment success of standard regimens under trial conditions in drug-
succeptible Tb is 95 % in non- critically ill patients.
• Treatment success critically depends on adequate blood levels of anti TB
drugs, while pharmacokinetic variability to a single drug of the regimen
can cause treatment failure or induce drug resistance.
• Pharmacokinetics is extensively altered by physiological and
pathophysiological change during critical illness
• Multiple factors may influence pharmacokinetics in critically illness
patients ( intestinal absorbtion delayed, intestinal paralysis, ulcer
profilaxsis,enteral nutrition,and critical illness-associated change ofthe
microbiome.
• To avoid inadequate intestinal drug absorption, it appears pragmatic
to,at least initially untill gastrointestinal function is restored,
administer anti- TB drugs intrvenously to critically ill patients.
• The use of empirical intravenous fluoroquinolones was suggested to
improve survival of critically ill patients admited for pulmonary tb
mimicking severe commnity aquired pneumonia
• Rifampicin high dose ( 15 mg/kg/d ) + Fluoroquinolom ( Levo 20 mg /
kg/d )..improved survival of TB.
• Rifampicin + INH change the activity of cytocrome P450 isoenzymes
and are responsible for interaction with several drugs commonly
adminietered in crytical ill patient
• Drug level monitoring and dose adjustments of other drugs are
frequently necessary.
• Rifampicin may reduce blood level of selected second line anti-TB
drugs such as moxifloxacin
• Another key chalenge of anti-TB drugs relates to their side effects.
• INH- Induced peripheral neuropathy
• Ethambutol- Induced retrobulbar neutitis
• Rifampicin, INH, Pyrazynamid-Induced liver injury
• Drug Induced- may cause critical illness during the subsequent
treatment phase
 The use of Steroids
• Glucocorticoids alter the immune response to M .tb.
• Current evidence and guidelines suggest that adjunctive steroid
therapy reduces mortality and probably long-term sequelae in HIV-
negative patients with meningitis TB and pericarditis.
• The effects of steroids on mortality of patients with pulmonary or
extrapulmonary TB other than meningitis or pericarditis remain
controversial.
• A recent meta-analysis reported that steroid could decrease mortality
for all form TB…most consistent in patients with a high disease severity
such as Miliary TB or TB-associated septic shock
• Adrenal Insufficientcy can be causes by exaggerated pro-inflamatory
response,tuberculous infiltration, or adrenal haemorhage.
• Rifampicin increase cortisol metabolsm and can precipitate
hypocortisolism
• The incidence of adrenal insufficiency in critically ill patients with TB is
unclear
• Similarly, No Studies have addressed the question wheter steroid
replacement improve organ function and / or outcome in patients with
TB and criticall illness related corticosteroid insufficiency.
 Management of HIV-co Infected Patients
• HIV infection inceases the risk of TB infection/re-activation and death.
• TB accelerates HIV replication and disease progression.
• CD4 < 200 per cubic mm..the presentation of TB may atypical
• CD4 < 75 per cubic mm..pulmonary symptomsTB are usually absent and
mycobactemia with miliary TB common.
• Antiretroviral therapy increase treatment succes, significantly reduces all-
cause mortality and recurrence rate in M tb and co-infected patients.
• The WHO recommends initiation of antiretroviral therapy within the first
eight weeks after start of anti-TB treatment
• HIV-positive patents who are already on antiretroviral therapy at TB
diagnosis should be continued on antiretroviral without interuption
• All patients with M tb co-infection receive Trimethopim-sulfamethoxazole
profilaxis at this substantially reduced the risk of pneumocystis,
toxoplasmosis, malarial and bacterial infections,as well as mortality.
• The immune reconstitution inflammatory syndrome ( IRIS )is characterized by
worsening of clinical symptoms after initiation of antiretroviral therapy.
• Severe forms are rare but can manifest as increasing tuberculomas,
worsening of pulmonary gas exchange and ARDS… suggested that the
propensity to develop IRIS was linked to the quantity of mycobacteria in
circulation.
• No standard treatment for IRIS has been recommended.
• Management is usually symptomatic and includes steroid in severe cases.
 Infection Control and Preventing spread of
infection
• M tb bacilli are aerobic, non-spore forming and slow growing bacteria
which are resistant to severe adverse environmental conditions.
• Humans are the only reservoir for Mtb and it is predominantly spread
by airborne droplet expectorated ..of patients with pulmonary TB.
• Infection control measures are crucial to prevent infection of other
patients or staff.
• Rarely, Tb transmitted via ingestion, inoculation or vertical
transmission.
• One of the most important measures to prevent the spread of
infection is early diagnosis and rapid implementation of airborne
infection isolation.
• Infection control measures include isolation of patients with TB in single
room whose air should ideally be under negative pressure relative to the
other and with air changes greater than six times per hour or more.
• Staff should adhere to strict hand hygiene standards and wear N95 ( FP2)
masks when entering the room.
• N98 ( FP3 ) masks should be worn during handling of respiratory secretion,
in-or extubation.
• Closed suction systems and filters ( in expiratory limb ) should be used in
mechanically ventilated patients.
• Diagnostic and therapeutic interventions outside of the isolation are should
be kept a minimum, particularly in patients with MDR-TB.
• Spontaneously ventilatoring patients should wear a surgical mask when
leaving the isolation room.
• De-escalation of isolation can occur when three consecutive sputum
smear microscopy are negative.
• Pragmatically, de-isolation may be considered after 2 week-course of
anti TB drugs, however diabetic patients , patients with drug resistance
can be smear positive for longer periode of isolation.
• High-level room disinfection ( including ultraviolet light ) is
recommended for adequate environmental decomentation.
• Suspected or confirmed cases must be reported to regional or national
health departments and active contact tracing of household members
performed.
 Conclusions
• Acute Respiratory Failure, septic shock and multi organ dysfunction are
the most common reasons for intensive care unit admission of adult and
paediatric patients with active tuberculosis.
• The mortality of patients with confirmed TB requiring intensive care is
high ( > 68.7 % )
• Infection withmulti-drug and extensively resistent strains of MTB carries
an exceptionally high mortality and growing challenge in many parts of
the world.
• To avoid inadequate intestinal drug absorbtion administer anti – TB
drugs intravenously until gastrointestinal function is restored.

• Adjunctive steroid therapy reduces mortality in tuberculous meningitis

and reduces constrictive pericarditis. It is unclear wheter steroid may
benefit other form of tuberculosis
THANK YOU