-
8/17/2019 FullText (88)
1/33
-
8/17/2019 FullText (88)
2/33
1
A retrospective descriptive study on pulmonary tuberculosis patients in ICU
By
Dr. Ho Ka Yee
This work is submitted to
Faulty of Medicine of the University of Hong Kong
In partial fulfillment of the requirements for
The Postgraduate Diploma in Infectious Diseases
PDipID (HK).
Date: 10th May, 2012
Supervisor: Dr. Susanna Lau
-
8/17/2019 FullText (88)
3/33
2
Declaration
I, Ho Ka Yee, declare that this dissertation represents my own work and it has not
been submitted to this or other institution in application for a degree, diploma or any
other qualifications.
I, Ho Ka Yee also declare that I have read and understand the guideline on “What is
plagiarism?” published by The University of Hong Kong and that all parts of this
work complies with the guideline.
Candidate: Ho Ka Yee
Signature: ______________________________________
Date: 10th May, 2012
-
8/17/2019 FullText (88)
4/33
3
Acknowledgement
I would like to thank my supervisor Dr. Susanna Lau for her kind support and
guidance in this research project.
-
8/17/2019 FullText (88)
5/33
-
8/17/2019 FullText (88)
6/33
5
Results
Eighty five patients were identified with active MTB in the study period. The
mean age was 55.1±1.7 years old. Twenty six (30.6%) of the patients were above 65
years old. Seventy one (83.5%) of the patients were male. Twenty one (24.7%) of the
patients had history of tuberculosis. Thirty two (37.7%) of the patients presented with
fever for more than 1 week; 35 patients (41.2%) presented with subjective weight lost
and 60% admitted to ICU due to respiratory failure. Sixty nine (81.2%) of the patients
were intubated. Fifty seven (67.1%) of the patients had at least four types of anti-TB
drugs started during hospitalization. Sixty (70%) of the patients had both isoniazid
and rifampicin included in their anti-TB regimen. Eleven (16.7%) of the patients
receiving anti-TB treatment were complicated with drug-induced hepatotoxicity.
Thirteen (15.3%) patients were diagnosed by physicians to have hospital acquired
pneumonia during ICU stay. The ICU all-cause mortality was 54.8% and the hospital
mortality was 58.8%.
-
8/17/2019 FullText (88)
7/33
6
Background
Tuberculosis is endemic in Hong Kong. There were 5,132 cases notified to the
Tuberculosis and Chest service of The Department of Health to have tuberculosis. The
all-cause mortality rate for this group of patients was 2.8 per 100, 000 populations in
2009 (1). There was a disproportionately large portion of the group was elderly
patients defined as older than 65 years old. The average age at MTB related death was
74.5 year old.
Intensive care support was required in 1-3% of all cases of tuberculosis and great
various clinical presentations were reported in overseas countries (3-4). However, we
do not have similar reported data in Hong Kong.
The TMH ICU, the largest ICU in Hong Kong, is a 26-bed mixed surgical and
medical intensive care unit. There were more than 8,000 cases admitted to the TMH
ICU during the study period. The average Acute Physiological and Chronic Health
Evaluation (APACHE) II scores of all admitted patients were between 18 and 19. In
2008, 10% of the reported TB cases diagnosed in Hospital Authority hospitals were
reported by TMH.
-
8/17/2019 FullText (88)
8/33
7
Study Objectives
To describe the demographic data, the all-cause mortality, the rate of developing
concomitant bacterial infection, the anti-tuberculosis drugs prescription pattern and
the rate of drug induced side effects such as hepatotoxicity in patients with
tuberculosis requiring ICU care.
-
8/17/2019 FullText (88)
9/33
8
Methodology
This is a retrospective study of critically ill patients with the diagnosis of active
MTB infection admitted to ICU of TMH in Hong Kong. The study period was
between January 2004 and December 2009. Adult patients older than 18 years old
diagnosed to have active MTB and admitted to TMH ICU during the study period
were recruited. With the assistance of microbiologists, patients admitted to ICU with
acid-fast bacilli (AFB) smear, AFB culture and TB polymerase chain (PCR) positivity
were identified. Patient’s hospital notes, Clinical Management system (CMS) record,
Elective Record (ePR) and ICU Clinical Information System (CIS) were reviewed.
Continuous values are expressed in mean ±SD. Categorical variables are presented as
number or percentage (%) in the tables and texts.
-
8/17/2019 FullText (88)
10/33
9
Results
Baseline characteristics and disease presentation of the patients
Socio-demographic data
The total number of patients included in this study is 85. The mean age of
patients is 55.1±1.7 years and twenty six (30%) of patients are above 65 years old.
Seventy-one (83.5%) was male. Fifty two (61.2%) of patients were smoker and thirty
one (36.5%) of them were drinker. Twenty nine (34.1%) of them were single and
thirty one (36.5%) were unemployed. Eight (9.4%) of patients were non-Chinese and
seven (8.2%) were new immigrants. (Table 1)
Co morbidities
Only one (1.2%) patients had co-existing HIV infection and 1 (1.2%) patient has
scoliosis. Twenty one (24.7%) patients had history of tuberculosis. Eight (9.5%)
patients had bronchiectasis; 16 (18.8%) patients had chronic obstructive pulmonary
disease (COPD); 6 (7.1%) patients had interstitial lung diseases and 2 (2.4%) patients
were on long term oxygen therapy. Eleven (12.9%) patients had diabetes mellitus and
4 (4.7%) of them on insulin therapy. Three (3.5%) patients were dialysis dependent
for chronic kidney failure and 5 (5.9%) had liver cirrhosis. Chronic hepatitis was
noted in 8 (9.4%) patients. Six (7.1%) patients were put on long-term steroid or
immunosuppressant therapy. (Table 1)
-
8/17/2019 FullText (88)
11/33
10
Table 1.Summarizing the socio-demographic data and co morbidities
Total number of patients 85
Data Number of patients Percentage (%)
Male 71 83.5
Smoker
Current smoker
52
28
61.2
32.9
Drinker
Current drinker
31
17
36.5
20
Single 29 34.1
Unemployed 31 36.5
Non- Chinese 8 9.4
New immigrants 7 8.2
Co-existing HIV infection 1 1.2
Scoliosis 1 1.2
History of TB 21 24.7
Bronchiectasis 8 9.5
Chronic obstructive lung disease 16 18.8
Interstitial lung disease 6 7.1
Long term O2 therapy 2 2.4
Diabetes mellitus 11 12.9
On insulin 4 4.7
Dialysis dependent 3 3.5
Liver cirrhosis 5 5.9
Chronic hepatitis 8 9.4
Long term immunosuppressant 6 7.1
-
8/17/2019 FullText (88)
12/33
11
Disease presentation
Nineteen (22.4%) of patients presented with reduced appetite; 35 (41.2%) had
weight lost and only six patients (7.1%) complained of night sweating. Forty five
(52.9%) were feverish and 32 (37.7%) of them had fever more than one week. Sixty
one (71.7%) of patients complained of shortness of breath and 50 (58.8%) had it for
more than one week. Only 11 (12.9%) patients presented with hemoptysis.
Thirty nine (45.9%) patients were suspected to have MTB within 24 hours of
hospitalization.
Most of the patients admitted for ICU support were due to respiratory failure (53,
62.4%) and unstable hemodynamics (9, 10.6%). The remaining patients were
admitted with the primary reasons of neurological symptoms, diabetes ketoacidosis,
hemoptysis or post-operative care. (Table 2)
Intubation and mechanical ventilation
Sixty-nine out of 85 patients (81.2%) were intubated and put on mechanical
ventilator during ICU stay. (Table 2)
-
8/17/2019 FullText (88)
13/33
12
Table 2. Summarizing the disease presentation
Symptoms Number of patients Percentage (%)
Night sweating 6 7.1
Fever
More than 1 week
45
32
52.9
37.7
Shortness of breath
More than 1 week
61
50
71.7
58.8
Haemoptysis 39 45.9
Suspected MTB within
24 hours of hospitalization
39 45.9
Admitted ICU due to
Respiratory failure
Shock
53
9
62.4
10.6
Undergoing invasive mechanical
ventilation
69 81.2
-
8/17/2019 FullText (88)
14/33
13
Investigations
There were 73 sputum samples and 36 (49.3%) were smear and culture positive
while 28 (38.4%) were culture positive only. Among the 37-bronchoalveolar lavage
samples, 14 (37.8%) were smear and culture positive while 20 (54%) were culture
positive only. There were 38 bronchial samples sent for TB PCR, 25 (65.8%) were
positive. Among the patients with positive TB PCR results, 12 of them were open TB
with positive AFB culture; 2 were culture positive only. Among the patients with
negative TB PCR results, 1 of them were open TB with positive AFB culture and 6
were culture positive only. (Table 3)
There were great variations in radiological features. 11 (12.9%) out of 85
patients developed cavitations and 15 (17.6%) cases showed military CXR pattern.
Eight (9.4%) patients had no consolidation on CXR; 13 (15.3%) had haziness over 1
quadrant, 22 (25.9%) had haziness over 2 quadrants, 11 (12.9%) had haziness over 3
quadrants and 27 (31.8%) had consolidation over 4 quadrants. Fifty nine (69.4%) of
CXR showed upper zone involvement.
-
8/17/2019 FullText (88)
15/33
14
Table 3. Summarizing the microbiological sample results
Sputum/
tracheal aspirate
Bronchoalveolar lavage
Total 73 37
Smear & culture positive 36 (49.3%) 14 (37.8%)
Culture positive only 28 (38.4%) 20 (54.1%)
Negative 9 (12.3%) 3 (8.1%)
Positive
Positive TB-PCR Negative TB-PCR
Total number 25 13
Smear &culture positive 12 (48.0%) 1 (7.8%)
Culture positive 2 (8%) 6 (46.2%)
Culture negative 11 (44.0%) 6 (46.2%)
-
8/17/2019 FullText (88)
16/33
15
Drug resistance rate
The mono-resistance rate to isoniazid (H) was 6.2% and to streptomycin (S) was
14.8%. There was 2.5% resistance to rifampicin (R) and 1.2% resistance to
ethambutol (M). (Table 4)
Table 4. Summarizing the drug resistant rate of current study compared with
data presented in 2008 Annual report
Resistance Current Study
(n=85)
General HK population
2008 Annual report
Mono-resistance to H
Mono-resistance to R
Mono-resistance to S
Mono-resistance to M
6.2%
2.5%
14.8%
1.2%
2.22%
0.21%
4.50%
0.07%
(H=isoniazid, R=rifampicin, S=streptomycin, M=ethambutol)
Anti-tuberculosis treatment regimens
Sixty-six patients had anti-TB treatment prescribed during the current
hospitalizations. Most of the patients had 4 drugs prescribed during their
hospitalization period. For maximum number of drugs used during ICU stay, 1 case
received 2 drugs, 8 cases received 3 drugs, 46 cases received 4 drugs, and 11 cases
received 5 drugs. For minimum number of drugs used during ICU stay, 1 case
received 1 drug, 4 cases received 2 drugs, 21 cases received 3 drugs, 38 cases
received 4 drugs and 2 cases received 5 drugs. Concerning the best regimen during
hospitalization, 5 patients received non-HR containing regimen, 1 patient received H
-
8/17/2019 FullText (88)
17/33
16
or R only, 10 patients received H and R containing regimen, and 50 patients had H, R
and Z containing regimen. For the poorest regimen during hospitalization, 12 cases
received neither H nor R, 7 cases received only H or R, 12 cases received H and R
containing regimen, and 35 cases received H, R and Z regimen.
Those patients received less than or equal to 3 anti-TB drugs containing regimen were
associated with higher mortality. There were 57 patients received more than 3 anti-TB
drugs in their regimen and 34 (59.7%) of them died while 9 patients received less than
or equal to 3 anti-TB drugs and 100% of them died.
Treatment related complications
There were 11 (11/66, 16.7%) patients diagnosed to have anti-TB drug related
hepatotoxicity based on clinical and serial liver function tests during hospitalization.
One (1/66, 1.5%) patient diagnosed to have renal toxicity by clinician and one patient
had ocular toxicity due to ethambutol. There were 6 (6/66, 9.1%) patients had
documented anti-TB treatment related thrombocytopenia, 1 (1/66, 1.5%) patient had
documented anti-TB treatment related eye side effect.
Rate of developing concomitant bacterial infection
There were 13 (15.3%) patients diagnosed by physicians to have nosocomial
pneumonia during ICU stay.
-
8/17/2019 FullText (88)
18/33
17
All-cause mortality
The hospital mortality of MTB patients requiring ICU care is much higher than
that of the patients managed in general medical wards. This is particularly prominent
for the subgroup of patients requiring organ supports especially mechanical ventilator
support. The all-cause ICU mortality is 54.8% and their hospital mortality is 58.8%.
There were 81.2% of MTB patients admitted to ICU requiring intubation and invasive
mechanical ventilator support. The mortality for this particularly group of patients is
up to 72.5%.
Disease severity as reflected by Acute Physiological and Chronic Health
Evaluation Score (APACHE II)
The total APACHE II score for all patients was 22.2±9.6. The APACHE score for
deceased patients was 26.1±8.6 and that for survived patient was 15.4±7.2.
-
8/17/2019 FullText (88)
19/33
18
Discussion
This retrospective analysis of 85 MTB patients admitting intensive care found an
in-hospital mortality rate of 58.8% and the hospital mortality among patients requiring
mechanical ventilation was 72.5%. Most of the patients died within the first 20 days
of ICU admission. Previous reported mortality rate ranged from 60% to 80%. Those
reporting higher mortality rate mainly recruited patients suffered from miliary
tuberculosis and severe acute respiratory distress syndrome (ARDS).
Eighty-four percent of the patients were male. This sex bias is observed in most
parts of the world and is reported in many large prevalence surveys. There are many
postulated reasons for this phenomenon. Biological differences such as sexual
hormones, genetic regulation and metabolism, make men more susceptible to and
development of MTB diseases. Other factors include the role of aging, migration of
workforce from the mainland China and tobacco consumption.
Only 20% of patients are current drinker in this review, the percentage is much
lower than the western MTB patients. (4) Nonetheless, smoking is more common in
deceased group. Smoking affects the clinical manifestations of MTB by increasing the
cavitary and miliary disease and rate of positive sputum culture (5-7). It is because of
the reduction in regulation of macrophage TNF alpha in lung may make the patient
more susceptible to severe MTB disease.
-
8/17/2019 FullText (88)
20/33
19
Thirty-five (41.2%) patients complained of recent weight lost or were described
as wasted or malnourished by clinicians on admission. Malnourished patients are
prone to MTB because starvation reduces the phagocytic ability of pulmonary
alveolar macrophages, which is important in local cellular defenses of pulmonary
system. It is also well known that it is an important predictor of mortality. Hence,
early and aggressive attention to improve the nutritional status is an important
treatment to reduce the mortality of MTB in ICU (8-9).
There are only one patient had HIV-TB co-infection in the studied population. It
is far more less than the rate reported in western countries like the United States. The
Centers for Disease Control and Prevention estimated that 16% of TB cases among
aged 25 to 44 are HIV-infected persons. While the rate of HIV sero-positivity in TB
patients amongst European regions was 3% according to WHO registry (10). In Hong
Kong, there were total 44 cases with TB-HIV co-infection reported from various
sources under Hong Kong TB-HIV Registry in 2008. This marked difference can be
further explained by the fact that HIV testing is performed in the Chest Clinic in a
voluntary basis; this may be resulted in undiagnosed HIV/ AIDS and TB co-infection.
Fifty three (62.4%) of the patients were admitted to ICU due to respiratory failure
(defined as PaO2< 8 kPa or SpO2< 90%, with or without pCO2>6 kPa, requiring high
flow oxygen support, mechanical ventilation or noninvasive ventilation). Sixty nine
-
8/17/2019 FullText (88)
21/33
20
(81.2%) patients of the admitted group ended up requiring intubation and mechanical
ventilation support. The mortality of these patients was expected to be worse than
those required O2 therapy only. Their mortality was up to 72.5% and this is coherent
with the pattern reported in the Western studies.
Accurate and early diagnosis of both TB and MDR TB are important for
containing the disease. Diagnostic delay and improper treatment leading to acquired
drug resistances and increased transmission rate are observed worldwide. However,
only half of the patients were suspected to have MTB within the first 24 hours of
hospitalization. Also, the diagnosis of MTB is usually difficult just based on the
nonspecific clinical symptoms and CXR findings.
Forty nine percent of TA or sputum and 37.8% of BAL specimens are positive
for AFB smear in the study group. It is approximately the same as WHO reported
figure 44% (11).
In TMH, we employ Auramine O staining (AO staining) as a screening test,
which is on average 10% more sensitive than conventional microscopy. The slides
with positive result using AO stain will be treated with Kinyoun’s carbolfuchsin stain
again and examined under light microscopy. Microscopic examination of smear is
rapid and inexpensive, however, only 34-80% of expectorated sputum samples are
positive and it is often negative in HIV-co infected patients due to their atypical
-
8/17/2019 FullText (88)
22/33
21
presentations (11).
We use both liquid and solid media for culture. Liquid cultures are more rapid
and sensitive than solid medium (12).
We also feature a rapid culture modality using the Bactec system. In the
incubator, Mycobacteria that present will metabolize the nutrients and consume the
oxygen. A built-in fluorescent sensor will reflect the concentration of dissolved
oxygen in the medium. A photo detector measure the level of fluorescence
corresponding to the amount of oxygen consumed. Those bottles with positive signals
will then be examined using AFB staining method to confirm the presence of
mycobacterium. It takes 7-12 days for growth.
PCR amplification is commonly used to identify MTB patients. The results are
available within 1 day. For the samples with positive AFB smear, the sensitivity of
PCR to detect MTB is greater than 95% (13). It can be used to confirm MTB
infection. On the other hand, for patients with negative AFB smears, the sensitivity of
PCR is heterogeneous and is not consistently good enough to be used to confirm the
diagnosis of tuberculosis (14). False positive occurs in patients with history of
tuberculosis and with bronchogenic carcinoma. Rarely, a positive AFB smear together
with a negative PCR indicates non-tuberculous mycobacteria infection. A prospective
multicenter TBNET study concluded that patients with AFB smear negative
-
8/17/2019 FullText (88)
23/33
22
pulmonary MTB can be distinguished from patients with latent MTB by local
immune-diagnosis with Mycobacterium tuberculosis- specific enzyme-linked
immunospot test on BAL fluid with sensitive of 91% and specificity of 80% (15).
Interferon gamma release assays evaluate the presence of persistent
mycobacterium-specific T cell response. However, it cannot differentiate patients with
active, past or latent tuberculosis. It is superior then tuberculin skin test in
immune-compromised patients. The negative predictive value of this test combined
with TST is 95%. Hence, it is a useful tool to rule out active tuberculosis. But we do
not have the routine assay in detecting interferon gamma release for rapid testing in
local hospital.
Other novel diagnostic tests include the use of mycobacteriophages to identify
MTB from specimen, which requires only 2 days of turnover time, it has high
sensitivity (83-100%) but low specificity (21-88%) and is not available in local practice.
New biomarkers like interferon-induced protein IP 10, CXC chemokine and monocyte
chemo-attractant protein MCP-2, a CC chemokine have also been clinically evaluated
yet still not widely available.
High-resolution computer tomography (HRCT) can be used to assist the
diagnosis if CXR is atypical (16). Features suggesting MTB include centrilobular
nodules, tree- in- bud opacities, lobar consolidation, calcified granuloma, cavitation
-
8/17/2019 FullText (88)
24/33
23
and bronchial wall thickening involving upper lobes or upper segment of lower lobes
(17, 18). Sixteen (18.8%) patients had HRCT done to assist the diagnosis of MTB.
Those HRCT mainly reviewed consolidations and one of them showed tree-in-bud
opacities.
The practice of directly observed treatment, short course effectively reduced the
drug resistance problem in the local community in Hong Kong. However, global
emergence of MDR-TB and extremely drug resistant tuberculosis (XDR-TB) are
posing challenges in TB control. As the major business and financial center in
Southeast Asia, Hong Kong is particularly at risk due to the massive population flow
and relatively high rate of drug-resistance in nearby areas. According to the Annual
Report 2008, 90.64% of TB cases were susceptible to all 4 drugs. Mono-resistance to
isoniazid (H) was 2.22%, to rifampicin (R) was 0.21%, to ethambutol (E) was 0.07%
and to streptomycin (S) was 4.50%. Multi drug resistance rate was 0.49%. Resistance
to H and R was 0.07%, H, R, and E was 0.14, H, R and S was 0.07%, H, R, E and S
was 0.21% (19). In this study, the mono-resistance rate to H is 6.2%, to S is 14.8%
which are higher than that of general Hong Kong population.
Globally the highest level of resistance to anti-TB treatment is observed for
streptomycin (11) and we shared the same finding in our study. The resistance resulted
from misread mRNA and faulty protein synthesis.
-
8/17/2019 FullText (88)
25/33
24
The only proper way of management is early identification of these patients and
their minimal treatment is 18-24 months. The identification methods include HRCT
scan, phenotypic and molecular testing.
There are no well documented randomized control trials on the topic of optimal
regimen of anti-TB therapy for critically ill patients. Recommendations are essentially
copy from ambulatory general population. There are a lot of limitations on drug
prescription in ICU patients. Many of them develop ileus which highly affect the
bioavailability and hence the efficacy of enteric anti-TB drugs. Parental anti-TB drugs
have been used in these patients and the options are limited to rifampicin, isoniazid,
quinolone and amikacin.
The use of anti-TB drugs in ICU patients is associated with vast number of
problems. Significant deranged liver functions due to cholestasis, reactive hepatitis or
sepsis are common reasons for omitting some or all of the standard hepatotoxic drugs.
Drugs induced hematological side effects, renal derangement and drug-drug
interactions are reported. Last but not least, pharmacokinetics and pharmacodynamics
of anti-TB drugs are significantly altered in these populations. Clearance of drugs is
also affected by renal replacement therapy.
All these are reason explaining why it may not be possible to prescribe the
standard anti-TB regimen at the beginning and many a time, there are changes in the
-
8/17/2019 FullText (88)
26/33
-
8/17/2019 FullText (88)
27/33
26
treatment failure include the presence of cavitation together with positive smear and
culture, non-adherence to therapy, co-infection with HIV and history of previous
history of treatment with TB drugs. It is difficult to explore this outcome in current
study because the survivors were discharged to chest hospital or clinic for further
follow-up.
Drug induced liver injury is a spectrum comprising hepatic adaptation; drug
induced acute hepatitis, nonalcoholic fatty liver disease, hepatocellular injury,
granulomatous hepatitis and cholestasis. It is diagnosed by exclusion. There are
different definitions of hepatotoxicity used in published trials. In local data, the
case-fatality rate among cases older than 65 years was 6.5% and half of them had
history of hepatitis B (10). A meta-analysis had shown that the incidence of liver
toxicity was 2.6% with isoniazid and rifampicin co-administration, but only 1.1%
with rifampicin alone and 1.6% with isoniazid alone (21). The observed increase in
hepatotoxicity in the combined treatment of isoniazid and rifampicin can be explained
by the induction of liver enzymes, which enhance isoniazid metabolism causing
accumulation of toxic isoniazid metabolites. Hepatotoxicity due to pyrazinamide is
also observed and is dose related. Hence, authorities suggested the use of lower daily
dose or thrice-weekly regime (22).
The American Thoracic Society (ATS) recommends that TB treatment should be
-
8/17/2019 FullText (88)
28/33
27
interrupted when ALT > 3 X UNL in the presence of symptoms or total bilirubin > X
2 UNL; or ALT > 5 X UNL with or without symptoms. By reviewing the statistics,
three non-survivors had ALT > X 3 UNL and total bilirubin > X 2UNL during the first
week of anti-TB treatment. One survivor and 5 non-survivors had ALT X 5 > UNL
during the first week of anti-TB treatment. It is difficult to diagnose drug induced
hepatotoxicity in ICU patients because deranged liver function test can be
multi-factorial like sepsis, antibiotics related, biliary sepsis, TPN related, flare up of
hepatitis, shock liver, acalculus cholecystitis. None of the cases underwent liver
biopsy to diagnose anti-TB medication hepatitis and this is not a usual local practice.
By reviewing the case notes, there are 11 patients diagnosed to have anti-TB
medication hepatotoxicity based on clinical and serial LFTs. For the 11 patients
diagnosed to have anti-TB medication related hepatotoxicity. Eight of them had H, R
and Z containing regimen, 3 of them had H and R containing regime.
There are 6 documented anti-TB treatment related thrombocytopenia and 1
documented ocular toxicity due to ethambutol. Again, the diagnosis of drug-induced
thrombocytopenia is by excluding other possible etiologies such as sepsis, DIC,
hemolysis, heparin-induced thrombocytopenia, autoimmune diseases, and marrow
failure and so on. For the six patients diagnosed to have drug related
thrombocytopenia, four of them had H, R and Z containing regimen and 2 of them
-
8/17/2019 FullText (88)
29/33
28
had H and R containing regimen. For the one with drug induced ocular toxicity, he
had ethambutol in his treatment regimen.
The mean APACHE score of our patients is 22, which is significantly higher than
that of the previous trials with APACHE ranging from 13 to 16 (4, 23). It is similar to
one study focused on ARDS caused by MTB in ICU (24). However, it is well known
that APACHE II is good predictor in populations but not for individual patients.
Furthermore, these score is developed in patient populations in which TB is probably
making up a very small proportion. Therefore, the prediction from these scores could
not be extrapolated to the patient sample of the current study.
Pitfalls of this study
Being a retrospective and single-centered study is the main limitation of this
work. The accuracy of raw data relies on the documentation of case medical officers
and the completeness of the database in our hospital. Certain important tests such, as
lactate level and echocardiogram, were not performed during the hospital stay.
Rapidly deteriorating patients were undermined during the case identification process
due to the failure to collect appropriate specimens. Furthermore, the ICU admission
rate depends on the local admission guidelines and affects the studied frequency of
admission and sample size achieved.
-
8/17/2019 FullText (88)
30/33
29
Conclusion
Mycobacterium tuberculosis infection is endemic disease in Hong Kong. Patients
with active tuberculosis infection requiring ICU admission carry very high mortality.
The diagnosis always poses a challenge to clinicians and so the index of suspicious
should be higher if patients develop symptoms days before hospital admission and in
immunocompromised patients due to their atypical presentations. Further multi-center
study aim at identifying predictive factors can help critical care physicians to formulate
plans of management and counsel patients’ relatives regarding the prognosis of MTB
patients receiving intensive support is encouraging.
-
8/17/2019 FullText (88)
31/33
30
Reference lists
1. Tuberculosis notifications and rate in 2010.
http://www.chp.gov.hk/en/data/4/10/26/43/458.html
2.
Trends in Tuberculosis-United States, 2010. Centers for Disease Control and
Prevention.
3.
Frame RN. Active tuberculosis in the medical intensive care unit: a 15- year
retrospective analysis. Crit Care Med. 1987 Nov; 15(11): 1012-4.
4. Erbes R. Characteristics and outcome of patients with active pulmonary
tuberculosis requiring intensive care. Eur Respir J 2006; 27(6): 1223-8.
5. Leung CC. Smoking and tuberculosis in Hong Kong. Int J Tuberc Lung Dis
2003, 7(10): 980-986.
6. Altet-Gomez. Clinical and epidemiological aspects of smoking and tuberculosis:
a study of 13, 038 cases. Int J Tuberc Lung Dis 2005, 9(4): 430-436.
7.
Chaing CY. Associations between tobacco and tuberculosis. Int J Tuber Lung
Dis 2007, 11(3): 258-262.
8. Mehta JB. Nutritional status and mortality in respiratory failure caused by
tuberculosis. Tennessee. Medicine. 1996:89(10): 369-371.
9.
D.K. Kim. Nutritional deficit as a negative prognostic factor in patients with
miliary tuberculosis. Eur Respir J 2008: 32: 1031- 1036.
10. Annual Report 2008. Tuberculosis & Chest Service of the Department of Health
Hong Kong. http://www.info.gov.hk/tb_chest/doc/Annual_Report_2008.pdf .
Assessed on Jan, 2010.
11.
WHO. Anti-tuberculosis drug resistance in the world: fourth global report.
-
8/17/2019 FullText (88)
32/33
31
http://www.who.int/tb/publications/2008/drs_report4_26feb08.pdf . Assessed on
Jan, 2010
12.
R.M. Anthony. Liquid culture for Mycobacterium tuberculosis: proceed, but
with caution. Int J Tuberc Lung Dis 13(9):1051-1053.
13.
Greco S. Current evidence on diagnostic accuracy of commercially based
nucleic acid amplification tests for the diagnosis of pulmonary tuberculosis.
Thorax 2006; 61:783-790.
14. Sarmiento OL. Assessment by meta-analysis of PCR for diagnosis of
smear-negative pulmonary tuberculosis. J Clin Microbiol. 2003; 41:3233-3240.
15. Jafari C. Bronchoalveolar lavage enzyme-linked immunospot for a rapid
diagnosis of tuberculosis. A Tuberculosis Network European trials group study.
Am J RespirCrit Care Med 2009. 180: 666-673.
16.
Sharma SK. Clinical profile, laboratory characteristics and outcome in miliary
tuberculosis. Q J Med 1995; 88(1), 29-37.
17. Kim HC. Multi drug-resistance tuberculosis versus drug-sensitive tuberculosis
in human immunodeficiency virus-negative patients: computed tomography
features. J Comput Assist Tomogr 2004; 28: 366-71.
18. Chung MJ. Drug sensitive tuberculosis. Multi drug-resistant tuberculosis and
nontuberculous mycobacterial pulmonary disease in non AIDS adults:
comparisons of thin section CT findings. EurRadiol 2006: 16: 1934-41.
19. Rao VK. The impact of co morbidity on mortality following in-hospital
diagnosis of tuberculosis. Chest 1998; 114:1244-1252.
20. American Thoracic Society CD Infectious Disease Society of America.
Treatment of tuberculosis. MMWR Recomm Resp 2003; 52:1-77.
21.
Steele MA. Toxic hepatitis with isoniazid and rifampin. Chest 1991; 99:465-71.
-
8/17/2019 FullText (88)
33/33
22. World Health Organization. Treatment of tuberculosis Guidelines for National
Programs. Fourth Edition.
http://www.who.int/tb/publications/cds_tb_2003_313/en/. Assessed on Jan, 2010.
23. Yon Ju RYU. Prognostic factors in pulmonary tuberculosis requiring
mechanical ventilation for acute respiratory failure.Respirology 2006, 12, 406-
411.
24.
Ritesh Agarwal. Experience with ARDS caused by tuberculosis in a respiratory
intensive care unit. Intensive Care Med 2005. 31:1284-1287.
