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Keywords:
Tuberculous meningitis
Mechanical ventilation
Chronic meningitis
Intensive care unit
Mortality
Outcome
a b s t r a c t
Purpose: There is paucity of information about the outcome of tuberculous meningitis (TBM) patients on mechanical ventilation (MV). In this communication, we report the clinical characteristics, predictors of MV, and
outcome of TBM patients requiring MV.
Method: Thirty-eight (18%) of 205 patients with TBM requiring MV were included; and their demographic, clinical, cerebrospinal uid, and magnetic resonance imaging nding at admission and follow-up were noted. The
ventilator-related and systemic complications, hospital death, and 3-month functional outcome were noted.
The predictors of need of MV were derived by multivariate regression analysis.
Results: There were 38 MV and 36 non-MV TBM patients who were matched for age, sex, and stage of meningitis
on admission. The requirement of MV was independently related to leukocytosis, seizure, and cerebrospinal uid
pleocytosis on admission. Patients on MV had higher frequency of septicemia (9 vs 2), bedsores (6 vs 0), and gastric hemorrhage (4 vs 0) compared with non-MV patients. Only 29% of MV patients survived and had poor outcome at 3 months; but in the non-MV group, all the patients survived, and only 11% had poor outcome.
Conclusion: Mechanical ventilation was needed in 18% TBM patients because of TBM-related or systemic complications. Those requiring MV had high mortality and may be categorized separately.
2015 Elsevier Inc. All rights reserved.
1. Introduction
Corresponding author at: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Rd, Lucknow, 226014. Tel.: +91 522 2494177;
fax: +91 522 2668811.
E-mail addresses: jayanteek@yahoo.com, jkalita@sgpgi.ac.in (J. Kalita).
http://dx.doi.org/10.1016/j.jcrc.2015.08.017
0883-9441/ 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Misra UK, et al, Outcome of tuberculous meningitis patients requiring mechanical ventilation, J Crit Care (2015), http://
dx.doi.org/10.1016/j.jcrc.2015.08.017
Table 1A
Comparison of demographic and clinical characteristics of tubercular meningitis patients
with and without MV
Sex (female/male)
Age (y)
Stage of TBM, I/II/III
Duration of illness (d)
GCS score
Focal motor decit
Seizures
Status epilepticus
Hypertension
Diabetes mellitus
Coronary artery disease
Renal failure
Liver dysfunction
Diagnosis
Denite/probable
PCR+
AFB+
Culture+
Ventilated (n = 38)
P value
15/23
35.9 12.6
1/15/22
74.3 65.5
9.8 3.3
24
24
7
9
5
1
5
0
13/23
37.1 16.6
1/18/17
68.5 66.6
11.0 2.7
18
11
3
20
4
2
0
1
.81
.72
.65
.71
.11
.35
.004
.21
.005
1.00
.61
.02
.49
.78
14/24
9/27
3/35
8/30
11/25
7/28
2/34
7/29
+, present.
to have raised intracranial pressure based on extensor posturing, hyperventilation, and pupillary asymmetry. Cranial nerve palsies and
papilloedema were noted. Muscle weakness was recorded as
monoplegia, hemiplegia, paraplegia, or quadriplegia. The severity of
weakness was graded as complete or partial. Muscle tone and tendon
reexes were graded as absent, normal, or increased. Stage of meningitis was categorized as follows [7]:
Stage I: meningitis only
Stage II: meningitis with focal neurological signs or GCS score 11 to 14
Stage III: meningitis with altered sensorium; GCS score less than 11.
2.2. Investigations
Blood counts, hemoglobin, erythrocyte sedimentation rate at rst
hour, blood glucose, serum creatinine, albumin, bilirubin, transaminases, and electrolytes were measured. Chest radiograph, electrocardiogram, and HIV serology were also done. Cranial MRI was done using a
3-T MRI scanner (Signa; GE Medical Systems, Milwaukee, WI). T1, T2,
uid attenuated inversion recovery, diffusion weighted image, and T1
contrast images were obtained in axial, coronal, and sagittal plain. Presence of exudates, hydrocephalus, infarction, and granuloma was noted.
Lumbar CSF was examined for cell, protein, and glucose. Cerebrospinal
uid smear and culture (BD BACTEC TM, BD, Sparks, MD) were done
for AFB. Cryptococcal antigen, immunoglobulin M enzyme-linked immunosorbent assay for M tuberculosis, and PCR were also carried out.
The patients were treated with rifampicin (10 mg/kg, ~450 mg), isoniazid (5 mg/kg, ~ 300 mg), pyrazinamide (20-25 mg/kg, ~ 1500 mg),
and ethambutol (15-20 mg/kg, ~ 800 mg) with prednisolone 0.5
Table 1B
Comparison of baseline laboratory prole of tubercular meningitis patients with and without MV
Parameters
Ventilated
(n = 38)
Non ventilated
(n = 36)
P value
Hemoglobin (g/dL)
Leucocyte count/mm3
Sodium (mEq/L)
Creatinine at admission (mg/dL)
Serum albumin (g/dL)
ALT (mEq/L)
AST (mEq/L)
Serum bilirubin (mg/dL)
CSF total cells/mm3
CSF proteins (mg/dL)
10.7 2.4
13 805.3 6798.3
132.4 8.0
1.1 0.9
3.2 0.8
120.0 119.2
117.7 118.2
0.8 0.4
210.9 251.7
222.0 243.7
11.5 1.8
9713.9 3838.8
133.49 7.3
0.9 0.8
3.5 0.6
101.1 135.2
88.5 91.6
1.0 0.9
78.4 94.4
171.5 174.7
.11
.002
.53
.44
.05
.53
.25
.26
.005
.34
Table 1C
Baseline MRI ndings of TBM patients who required MV and those who did not
Infarct
Tuberculoma
Hydrocephalus
Meningeal enhancement
Brainstem lesion
Posterior fossa lesion
Midline shift/herniation
Mechanically ventilated
n = 38
Not ventilated
N = 36
P value
20
13
15
11
4
6
1
15
17
19
14
3
6
1
.51
.46
.46
.55
.68
.74
.74
mg/kg (~40 mg) and aspirin 150 mg daily [9]. Prednisolone was tapered
after 1 month and stopped at the end of the second month. All the antitubercular drugs were given for 6 months followed by rifampicin and
isoniazid for an additional 1 year. Drug-induced hepatitis was diagnosed
on the basis of 3- to 5-fold rise in transaminase level after at least 3 days
of antitubercular treatment (ATT) without any other apparent cause for
liver dysfunction whose baseline liver function was normal. After discontinuation of hepatotoxic ATT, there was more than 50% improvement in liver functions. In these patients, ATT was modied and was
restarted sequentially when the transaminase level was less than 2
times the normal [10]. Patients with obstructive hydrocephalus with deteriorating consciousness were subjected to ventriculoperitoneal shunt.
The TBM patients were intubated and articially ventilated if unable
to maintain oxygen saturation by Ventimask or if there was respiratory
acidosis (pH b7.3), carbon dioxide retention (PaCO2 N 50 mm Hg), or
hypoxia (PaO2 b 60 mm Hg) [11]. Blood pressure, pulse, and oxygen saturation were monitored continuously. Arterial blood gas analysis (ABG)
was done daily or more frequently if indicated. Chest radiograph, blood
counts, and blood culture were done as indicated. The duration of MV,
ventilator-related complications (ventilator-associated pneumonia,
pneumothorax), and other complications (deep vein thrombosis, pressure sores, urinary tract infection, sepsis) were also noted.
From our TBM registry, 36 age- and stage-matched TBM patients on
admission who did not require articial ventilation were included as
controls.
2.3. Outcome
Complications during hospital stay were noted. Death during hospital stay and 3-month functional outcome of the surviving patients were
categorized on the basis of activity of daily living (ADL) as complete (independent for ADL), partial (partially dependent for ADL), and poor
(bed ridden or wheel chair bound) recovery [12].
2.4. Statistical analysis
The baseline clinical, laboratory, and MRI ndings between the TBM
patients with and without MV were compared using 2 for categorical
variables and independent t test or Mann-Whitney U test for continuous
variables. The predictors of MV were derived using logistic regression
analysis including the variables with a P value of b.10. The patients
with MV who died were compared with the surviving group with respect to their clinical, demographic, radiological, and ventilator-related
and systemic complications using 2, Mann-Whitney U test, or Student
t test. The predictors of death of MV patients were analyzed using logistic regression analysis. The variable was considered signicant if the
2-tailed P value was less than .05. The statistical analysis was done
using SPSS (Chicago, IL) 16 version software.
3. Results
During the study period, 205 patients with TBM were admitted and
38 (18.5%) of them needed MV. The median age of the MV patients was
32.5 (range, 17-65) years, and 15 (39.5%) were female. On admission,
Please cite this article as: Misra UK, et al, Outcome of tuberculous meningitis patients requiring mechanical ventilation, J Crit Care (2015), http://
dx.doi.org/10.1016/j.jcrc.2015.08.017
the majority of the patients belonged to stage II (15) and stage III (22)
meningitis; and only 1 patient was admitted in stage I TBM. The diagnosis of TBM was denite in 14 (36.8%) patients and probable in 24
(63.2%). The median duration of illness before hospitalization was 60
(range, 7-241) days, seizures were present in 24 (63.2%), and 7
(18.4%) of them had status epilepticus. The admission GCS score ranged
between 3 and 15 (median, 10) and was less than 8 in 10 (26.3%) patients. Focal weakness was present in 24 (63.2%) patients, hemiplegia
in 16 (42.1%), paraplegia in 3 (7.9%), and quadriplegia in 5 (13.2%). Cranial nerve palsies were involved in 5 (13.15%) patients. The comorbidities included hypertension in 9, diabetes in 5, coronary artery disease in
1, and renal failure in 5 patients. On admission, 20 (52.6%) patients were
anemic, 23 (60.5%) had hypoalbuminemia, 25 (65.8%) had hypocalcemia, and 16 (42.1%) had hyponatremia.
Table 2
Comparison of laboratory parameters during hospital stay (worst value) in TBM patients
who required MV and those who did not
Hemoglobin (g/dL)
Leucocyte/mm3
Serum albumin (g/dL)
Serum calcium (ionic) (mg/dL)
Serum sodium (mg/dL)
Serum bilirubin (mg/dL)
ALT (U/L)
AST (U/L)
CSF total cells/mm3
CSF protein (mg/dL)
Mechanically
ventilated
Not ventilated
P value
9.1 2.5
16 902 6329
2.6 0.6
4.0 0.5
128.1 6.6
1.5 2.3
235.1 252.2
191.9 155.6
210.9 251.7
222.0 243.7
10.6 1.9
11 578 5374
3.1 0.5
4.3 0.4
127.3 6.0
1.8 2.7
163.5 163.2
136.5 124.4
78.4 94.4
171.5 174.7
.007
.000
.001
.001
.596
.595
.155
0.099
0.005
0.338
Please cite this article as: Misra UK, et al, Outcome of tuberculous meningitis patients requiring mechanical ventilation, J Crit Care (2015), http://
dx.doi.org/10.1016/j.jcrc.2015.08.017
Table 3
Comparison of follow-up imaging (CT/MRI) ndings in MV and non-MV TBM patients
Imaging ndings
MV group
Non-MV group
P value
New infarct
New tuberculoma
Increase in tuberculoma size
New onset hydrocephalus
Increase in hydrocephalus
New onset herniation
10 (26.3%)
1 (2.6%)
1 (2.63%)
7 (18.4%)
7 (18.4%)
6(15.8%)
3(8.3%)
4 (11.1%)
1 (2.77%)
3(8.3%)
2(5.6%)
0 (0%)
.04
.15
.969
.21
.09
.01
4. Discussion
In the present study, 18.5% of patients with TBM needed MV because
of associated sepsis and pneumonia in 55.3% and because of TBMrelated complications such as raised intracranial pressure and
venticuloperitoneal shunt in the remaining 44.7% of patients. Presence
of sepsis, seizures, and CSF pleocytosis on admission predicted MV. Thirty percent patients with MV survived but had major neurological decit
at 3 months.
This study for the rst time reports the outcome of mechanically
ventilated TBM patients. The outcome of TBM has been reported to be
dependent on age, GCS score, stage of meningitis, hydrocephalus, infarction, and paradoxical response to ATT [4,12,13]. The mortality in TBM
may vary in different stages of meningitis, being worse in stage III and
stage II compared with stage I. The mortality of TBM in stage II and III
has ranged between 66% and 86% [13]. In a study from France in 270 patients with TBM, the mortality was 47.9% in patients receiving corticosteroids and 52.1% in those without corticosteroids. The case fatality
rate in stage III meningitis was 61.5% in the group who received corticosteroids and 74.1% in those who did not [14]. This highlights the high
4.1. Limitations
Fig. 2. The outcome of TBM patients who were mechanically ventilated (MV) and those
who were not (non-MV).
The present study is limited by its retrospective nature, and conservative protocol of intubation and monitoring. We have not done
intraarterial blood pressure and intracranial pressure monitoring; the
use of these types of monitoring however has not been established to
be benecial in ICU patients in a meta-analysis [23].
Please cite this article as: Misra UK, et al, Outcome of tuberculous meningitis patients requiring mechanical ventilation, J Crit Care (2015), http://
dx.doi.org/10.1016/j.jcrc.2015.08.017
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Please cite this article as: Misra UK, et al, Outcome of tuberculous meningitis patients requiring mechanical ventilation, J Crit Care (2015), http://
dx.doi.org/10.1016/j.jcrc.2015.08.017