Nebulized lignocaine for topical anaesthesia in no-sedation bronchoscopy (NEBULA): A randomized, double blind, placebo-controlled trial

Abstract

Background:
The role of nebulized lignocaine administration for flexible bronchoscopy is unclear.

Methods:
In this randomized, double-blind, placebo-controlled trial, subjects undergoing diagnostic flexible bronchoscopy were randomized to receive either nebulized lignocaine (2.5 ml of 4% lignocaine) or nebulized (2.5 ml of 0.9%) saline (placebo). All received 10% lignocaine pharyngeal spray (4 sprays) and 5-ml nasal 2% lignocaine gel. 1% lignocaine solution was used for spray-as-you-go administration in all. Co-primary outcomes were Operator-rated overall procedure satisfaction and Operator-rated cough scores on Visual Analog Scale (VAS). Secondary objectives were cumulative lignocaine dose, proportion of subjects receiving >8.2-mg/kg lignocaine, and complications between the groups.

Results:
Two hundred and twenty subjects were randomized and 217 (109 - nebulized lignocaine and 108 - placebo) received the intervention. Baseline characteristics were comparable. Operator-rated overall procedure satisfaction scores on VAS (7.30 ± 1.54 nebulized lignocaine and 7.50 ± 1.31 placebo group,P = 0.85) and Operator-rated cough scores on VAS (3 [2-5] nebulized lignocaine and 3 [2-4] placebo group,P = 0.18) were similar. Cumulative lignocaine dose was significantly greater in nebulized lignocaine group (331.46 ± 9.41 mg vs. 232.22 ± 12.77 mg,P < 0.001), and a significantly greater number of subjects in this group received lignocaine dose >8.2 mg/kg. Minor complications occurred in 6 and 9 subjects in nebulized lignocaine and placebo groups, respectively,P = 0.41.

Conclusion:
Administration of nebulized lignocaine in addition to pharyngeal lignocaine spray, during no-sedation bronchoscopy, increases the cumulative lignocaine dose without improved procedural comfort. Additional nebulized lignocaine during bronchoscopy is not recommended.

Full text

Vol 36 I Issue 4 I July-August 2019
Official Publication of Indian Chest Society
Lung
India
Lung India • Volume 36 • Issue 4 • July-August 2019 • Pages 181-284
ISSN : 0970-2113
Editorial
Diaphragmatic dysfunction in chronic
obstructive pulmonary disease
Bharat Bhushan Sharma, Virendra Singh 285
Original Articles
Nebulized lignocaine for topical
anaesthesia in no-sedation
bronchoscopy (NEBULA): A randomized,
double blind, placebo-controlled trial
Karan Madan, Shiba Kalyan Biswal, Pawan Tiwari,
Saurabh Mittal, Vijay Hadda, Anant Mohan,
Gopi C Khilnani, Randeep Guleria 288
Alterations in body composition in
Indian patients with non-small cell
lung cancer
Anant Mohan, Rosemary Poulose, Ashraf Ansari,
Karan Madan, Vijay Hadda, GC Khilnani,
Randeep Guleria 295
Study of the diaphragm in chronic
obstructive pulmonary disease using
ultrasonography
Sanket Jain, Girija Nair, Abhishek Nuchin, Abhay Uppe 299
Neurocognitive and behavioral
abnormalities in Indian children with
sleep-disordered breathing before and
after adenotonsillectomy
Elias Mir, Rohit Kumar, Tejas M Suri,
Jagdish Chandra Suri, VP Venkatachalam,
Manas Kamal Sen, Shibdas Chakrabarti 304
The clinico-radiological profile of
obliterative bronchiolitis in a tertiary
care center
HS Suhas, Ketaki Utpat, Unnati Desai,
Jyotsna M Joshi 313
Prognostic influence of toll-like
receptor 4 gene polymorphism into
community-acquired pneumonia
course among young patients with
cytomegalovirus persistence
Larysa V Moroz,
Kiarina D Chichirelo-Konstantynovych,
Tetyana V Konstantynovych, Veronika M Dudnyk 319
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improve patient comfort include sedation and topical
anesthesia. Unlike majority of centers in North America and
Europe, “no-sedation” bronchoscopy is the most common
practice in certain regions including Japan and India.[1]
INTRODUCTION
Optimization of patient comfort is important during
bronchoscopy. Inadequate topical anesthesia and
poor cough control may be associated with operator
dissatisfaction and suboptimal procedure. Strategies to
Original Article
Background: The role of nebulized lignocaine administration for exible bronchoscopy is unclear. Methods: In this
randomized, double‑blind, placebo‑controlled trial, subjects undergoing diagnostic exible bronchoscopy were randomized
to receive either nebulized lignocaine (2.5 ml of 4% lignocaine) or nebulized (2.5 ml of 0.9%) saline (placebo). All
received 10% lignocaine pharyngeal spray (4 sprays) and 5‑ml nasal 2% lignocaine gel. 1% lignocaine solution was
used for spray‑as‑you‑go administration in all. Co‑primary outcomes were Operator‑rated overall procedure satisfaction
and Operator‑rated cough scores on Visual Analog Scale (VAS). Secondary objectives were cumulative lignocaine
dose, proportion of subjects receiving >8.2‑mg/kg lignocaine, and complications between the groups. Results: Two
hundred and twenty subjects were randomized and 217 (109 – nebulized lignocaine and 108 – placebo) received
the intervention. Baseline characteristics were comparable. Operator‑rated overall procedure satisfaction scores on
VAS (7.30 ± 1.54 nebulized lignocaine and 7.50 ± 1.31 placebo group, P = 0.85) and Operator‑rated cough scores
on VAS (3 [2–5] nebulized lignocaine and 3 [2–4] placebo group, P = 0.18) were similar. Cumulative lignocaine dose
was signicantly greater in nebulized lignocaine group (331.46 ± 9.41 mg vs. 232.22 ± 12.77 mg, P < 0.001), and a
signicantly greater number of subjects in this group received lignocaine dose >8.2 mg/kg. Minor complications occurred
in 6 and 9 subjects in nebulized lignocaine and placebo groups, respectively, P = 0.41. Conclusion: Administration
of nebulized lignocaine in addition to pharyngeal lignocaine spray, during no‑sedation bronchoscopy, increases the
cumulative lignocaine dose without improved procedural comfort. Additional nebulized lignocaine during bronchoscopy
is not recommended.
KEY WORDS: Bronchoscopy, cough, lignocaine, nebulization
Nebulized lignocaine for topical anaesthesia in no-sedation
bronchoscopy (NEBULA): A randomized, double blind,
placebo-controlled trial
Karan Madan, Shiba Kalyan Biswal, Pawan Tiwari, Saurabh Mittal, Vijay Hadda, Anant Mohan, Gopi C Khilnani,
Randeep Guleria
Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India
ABSTRACT
Address for correspondence: Dr. Karan Madan, Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, Ansari Nagar,
New Delhi ‑ 110 029, India. E‑mail: drkaranmadan@gmail.com
Access this article online
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DOI:
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How to cite this article: Madan K, Biswal SK, Tiwari P, Mittal S,
Hadda V, Mohan A, et al. Nebulized lignocaine for topical anaesthesia
in no-sedation bronchoscopy (NEBULA): A randomized, double blind,
placebo-controlled trial. Lung India 2019;36:288-94.
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Madan, et al.: Nebulized lignocaine in bronchoscopy
Lung India • Volume 36 • Issue 4 • July-August 2019 289
Adequate topical anesthesia is paramount in bronchoscopy
performed without sedation. Lignocaine is the most
commonly used drug for topical anesthesia. Although
uncommon, toxicity related to topical administration of
lignocaine has been reported; therefore, minimization of
lignocaine dose during bronchoscopy is important.[2]
Lignocaine is usually administered to the nasal cavity,
the pharynx, and the vocal cords – tracheobronchial tree
during bronchoscopy. The role of nebulized lignocaine
during bronchoscopy is controversial, and the British
Thoracic Society Bronchoscopy Guidelines do not
favor its use.[3] A recent study (the lignocaine in flexible
bronchoscopy (LIFE) randomized trial, 500 participants,
92% procedures performed without sedation) demonstrated
the feasibility of performing flexible bronchoscopy without
the administration of nebulized lignocaine though the
primary objective of the study was to compare two
different lignocaine concentrations.[4] In the setting
of bronchoscopy performed with combined sedation,
no benefit in procedural comfort or cough and higher
cumulative lignocaine exposure with nebulized lignocaine
administration was observed.[5] A recent small-sample
randomized controlled trial (RCT) (30 participants)
reported lower lignocaine and fentanyl requirements with
nebulized lignocaine and no differences between patient
tolerance and safety. Other studies have demonstrated
benefits such as faster procedure, greater patient
preference, reduced additional lignocaine requirements,
and lower serum lignocaine levels with administration
of nebulized lignocaine during bronchoscopy. There are
concerns that nebulized lignocaine administration might
increase the cumulative lignocaine dose received without
any improvement in patient comfort. There is a correlation
between total lignocaine dose administered during
bronchoscopy and plasma lignocaine levels; therefore,
minimization of lignocaine exposure during bronchoscopy
is important.[6] We hypothesized that nebulized lignocaine
administration to subjects undergoing bronchoscopy
without sedation is not associated with greater procedural
comfort as evaluated by operator-rated assessments of
overall procedure satisfaction and cough during the
procedure.
METHODS
The NEBUlized Lignocaine for Airway
anaesthesia (NEBULA) study was an investigator-initiated,
nonfunded, randomized, double-blind, placebo-controlled
trial. The trial was prospectively registered with the
clinicaltrials.gov registry (NCT03040193). Ethical approval
was obtained from the Institute Ethics Committee (Ref.
No. IEC-594/05.01.2017). Written informed consent was
obtained from all the subjects before randomization.
Consecutive subjects aged 18 years or older and planned for
flexible bronchoscopy who were willing for participation
and randomization were included in the study. The
following were exclusion criteria: (a) pregnancy, (b)
hypoxemia (oxygen saturation [by pulse oximetry] <92%
while breathing Oxygen at Fio2 of ≥0.3), (c) bronchoscopy
performed through endotracheal or tracheostomy
tube, (d) refusal of consent, (e) subjects planned for
administration of upfront sedation, and (f) subjects with
documented hypersensitivity to lignocaine. Subjects
willing for participation were randomized in a 1:1 ratio
to receive nebulized lignocaine or normal saline (placebo)
nebulization. Randomization sequence was computer
generated in block size of 10. Group allocation was
concealed in sealed envelopes.
Baseline demographic characteristics (age, gender, and
weight) were recorded for all subjects. Before procedure
initiation, blood pressure, oxygen saturation, respiratory
rate, and heart rate were recorded for all and monitored
continuously during the procedure. Subject preparation
was similar in both the groups apart from the administration
of either nebulized lignocaine or saline. Intravenous access
was routinely secured and none of the subjects received
anticholinergic premedication, dextromethorphan, or
other premedication agents. All procedures were planned
without administration of upfront sedation. However,
sedation was allowed at bronchoscopist discretion during
the procedure, and the details of the same were recorded.
Baseline topical anesthesia regimen in all randomized
subjects before bronchoscope introduction included 4
sprays (10 mg/spray) of 10% lignocaine applied on the
pharynx along with intranasal administration of 5 ml of
2% lignocaine gel (equivalent to 100 mg of lignocaine). All
subjects underwent nasal bronchoscopy, and any failure
to negotiate bronchoscope nasally was noted. All subjects
received low-flow supplemental oxygen using a thin
nasopharyngeal catheter. 1% lignocaine solution was used
for spray-as-you-go administration, and the total baseline
spray aliquot volume was 9 ml (1.5-ml aliquots – 2 at the
vocal cords, 1 – trachea and carina each, 1 – each in the
right and left main bronchus). None of the subjects received
transtracheal/transcricoid lignocaine injection. Procedures
were performed by experienced operators (either faculty
or fellows) with each having experience of a minimum of
200 nasal flexible bronchoscopy examinations.
Subjects were randomized to receive either nebulized
lignocaine or nebulized saline. 2.5 cc of solution (either 4%
lignocaine or normal saline) were used for nebulization.
A dedicated assistant was assigned the responsibility of
group allocation. A compressor jet nebulizer (OMRON
Healthcare, India) with mouthpiece was used, and neither
the assisting bronchoscopy nurse nor operator was aware
of the group allocations. Nebulization was followed by
administration of pharyngeal spray and nasal lignocaine
gel administration. Separate nebulizer mouthpieces were
used for each subject and were sterilized before use.
Flexible bronchoscopy was performed using either the
Olympus BF-TE2 fiber-optic bronchoscope or Olympus
1T180 video bronchoscope (Olympus Corporation, Japan)
with insertion diameter of 5.9 mm. Administration of
additional lignocaine aliquots (spray as you go) was

Madan, et al.: Nebulized lignocaine in bronchoscopy
290 Lung India • Volume 36 • Issue 4 • July-August 2019
allowed at operator’s discretion, and the details of the
same were documented. The hemodynamic parameters
were monitored, and subjects were carefully monitored
for any adverse effects. After completion of procedure, the
bronchoscopist-rated overall procedure satisfaction and
bronchoscopist-rated cough were recorded on a 10-point
Visual Analog scale (VAS). The VAS for Operator-rated
overall procedure satisfaction was anchored between
“totally unsatisfactory (0)” to “very satisfactory (10).”
Similarly, the VAS for Operator-rated cough was anchored
between “no cough (0)’’ at one end and “worst cough (10)’’
at the other.
Statistical analysis
The study had two co-primary outcomes: Operator-rated
overall procedure satisfaction and Operator-rated cough
scores on VAS between the groups. The secondary
outcomes included cumulative lignocaine dose, number
of subjects receiving lignocaine dose >8.2-mg/kg body
weight, and complications between the groups. The sample
size was calculated based on an expected VAS score
for procedure satisfaction 7.2 in the control group with
standard deviation (SD) of 2.0. With alpha 0.05 and power
90%, 103 subjects were required in each arm. Data were
presented as mean ± SD or median (interquartile range)
for continuous variables and proportions for categorical
variables. Categorical variables were compared using
the Chi-square or Fisher’s exact tests while continuous
variables were compared using the t-test or Wilcoxon
rank-sum test. P < 0.05 was considered statistically
significant. Statistical analyses were performed using
STATA statistical analysis software V.9.0 (StataCorp,
College Station, Texas, USA).
RESULTS
Two hundred and twenty-nine subjects were screened
for randomization, and after exclusion of 9 subjects
who failed to meet the inclusion criteria, 220 subjects
were randomized. Three subjects were excluded after
randomization (2 subjects – one in each group had
elevated blood pressures before nebulization leading
to procedure cancellation and one patient in the saline
placebo group refused to undergo nasal bronchoscope
insertion). Two hundred and seventeen randomized
subjects (109 – nebulized lignocaine and 108 – nebulized
saline) underwent bronchoscopy according to the planned
protocol. The flow of subjects in the study is depicted in
the CONSORT diagram [Figure 1].
Baseline characteristics between the groups were
comparable [Table 1]. Majority of the subjects were male and
mean age was 48 years. Baseline hemodynamic parameters
were similar between the groups. Although a greater
number of subjects underwent transbronchial lung biopsy
in the nebulized lignocaine group (11 vs. 3 participants,
Figure 1: CONSORT diagram showing the ow of participants in the Nebulized Lignocaine for Airway Anesthesia study

Madan, et al.: Nebulized lignocaine in bronchoscopy
Lung India • Volume 36 • Issue 4 • July-August 2019 291
P = 0.03), overall a similar number of participants
underwent any bronchoscopic biopsy in the two groups (27
in nebulized lignocaine group vs. 28 in the saline group,
P = 0.84). Procedure duration was similar between the
groups.
There was no significant difference between the
co-primary outcomes: Operator-rated overall procedure
satisfaction and Operator-rated cough scores on
VAS between the two groups [Table 2]. Mean (SD)
Operator-rated overall procedure satisfaction scores
on VAS were 7.30 (1.54) in the nebulized lignocaine
group and 7.50 (1.31) in the nebulized saline group,
P = 0.85. Median (interquartile) range Operator-rated
cough scores on VAS were 3 (2–5) in the nebulized
lignocaine group and 3 (2–4) in the nebulized saline
group, P = 0.18. On analysis of secondary outcomes,
the overall cumulative lignocaine dose received in
the nebulized lignocaine group was significantly
greater (331.46 ± 9.41 mg vs. 232.22 ± 12.77 mg,
P < 0.001), and a significantly greater number of subjects
received cumulative lignocaine doses >6 mg/kg (64 vs.
10, P < 0.001) and >8.2 mg/kg (8 vs. 0, P < 0.01) in
the nebulized lignocaine group. More participants
required intraprocedural sedation in the nebulized
lignocaine arm (10 in nebulized lignocaine vs. 3 in the
saline arm) (P = 0.047). Procedure duration and subject
willingness to return for a repeat procedure were similar
between the two groups. Minor complications occurred in
6 (5.5%) and 9 (8.3%) subjects in the nebulized lignocaine
and saline groups, respectively, P = 0.41.
DISCUSSION
The findings of NEBULA study demonstrate that
additional nebulization with 4% lignocaine during
flexible bronchoscopy is not associated with greater
operator-rated procedure satisfaction or reduction in
cough and is associated with higher cumulative lignocaine
dose exposure in subjects undergoing no-sedation
bronchoscopy. In addition, there are no advantages in
terms of procedure duration and patient willingness to
return for a repeat procedure. Furthermore, more subjects
in the nebulized lignocaine arm required intraprocedural
Table 2: Primary and secondary outcomes between the two study groups
Outcomes Nebulized lignocaine group (n=109) Nebulized saline group (placebo) (n=108) P
Primaryoutcomes
Operator‑ratedoverallproceduralsatisfaction(VAS),mean±SD 7.30±1.54 7.50±1.31 0.85
Operator‑ratedcough(VAS),median(interquartilerange) 3(2–5) 3(2–4) 0.18
Secondaryoutcomes
Cumulativelignocainedose(mg);mean±SD 331.46±9.41 232.22±12.77 <0.001
Patientsreceivingdose>8.2mg/kg;n(%) 8(7.3) 0<0.01
Patientsreceivingdose>6mg/kg;n(%) 64(58.7) 10(9.3) <0.001
Complications;n(%) 6(5.5) 9(8.3) 0.41
Acceleratedhypertension 1 4
Bronchospasm 1 3
Hypoxia 2 0
Minorairwaybleeding 02
Excessivecough 2 0
Additionallignocaineadministrationduringprocedureabovethe
baselinedose;n(%)
3(2.7) 3(2.7) 0.99
Patientwillingnesstoreturnforrepeatprocedure;n(%) 83(76.2) 84(77.8) 0.76
VAS: Visual analog scale, SD: Standard deviation
Table 1: Baseline characteristics of the study participants
Parameter Nebulized lignocaine group (n=109) Nebulized saline group (placebo) (n=108) P
Age(years);mean±SD 47.08±15.70 48.94±16.48 0.80
Males;n(%) 77(70.6) 69(63.9) 0.29
Weight(kg);mean±SD 55.09±10.27 52.78±9.83 0.05
Baselineheartrate(beats/min);mean±SD 98.39±12.87 99.34±12.45 0.71
Baselineoxygensaturation(%);mean±SD 96.92±3.14 97.57±6.59 0.82
Baselinesystolicbloodpressure(mmHg);mean±SD 129.55±17.61 131.28±17.86 0.76
Baselinediastolicbloodpressure(mmHg);mean±SD 81.05±9.65 80.53±11.20 0.35
Intraproceduralsedation;n(%) 10(9.17) 3(2.78) 0.047*
Procedureduration(min) 10.60±4.63 10.63±4.73 0.52
Proceduresperformed
Anybiopsy:EitherTBLBorEBBorboth;n(%) 27 28 0.84
TBLB;n(%) 11 30.03*
EBB;n(%) 23 27 0.49
TBNA;n(%) 74 0.36
Airwayinspectionalone;n(%) 10 9 0.82
BAL/bronchialwashingsalone;n(%) 67 66 0.95
TBLB: Transbronchial lung biopsy, EBB: Endobronchial biopsy, TBNA: Transbronchial needle aspiration, BAL: Bronchoalveolar lavage

Madan, et al.: Nebulized lignocaine in bronchoscopy
292 Lung India • Volume 36 • Issue 4 • July-August 2019
sedation. Therefore, additional nebulized lignocaine is not
required during no-sedation bronchoscopy.
Nebulized administration of local anesthetics for
bronchoscopy, especially lignocaine, has been actively
studied over the past three decades. The summary of
studies evaluating the role of nebulized local anesthetics
during bronchoscopy is summarized in Table 3. Palva et al.
demonstrated efficacy and better patient acceptability
in subjects undergoing bronchoscopy with nebulized
lignocaine administration, and since then, studies have
evaluated the role of nebulized lignocaine in randomized
designs.[7] Palva et al. also demonstrated earlier attainment
of peak serum levels with administration of nebulized
lignocaine, and this may be relevant as delayed peak and
toxicity can occur with spray administration (potentially
when patient might have left the bronchoscopy room).
Due to topical action, nebulized lignocaine was also
described as a treatment option for intractable cough.[8]
The preliminary observations were contradicted by the
first RCT comparing nebulized lignocaine administration
with laryngotracheal spraying, (Korttila et al., 1981)
wherein the efficacy of local anesthesia and patient
cooperation were superior with spray administration of
lignocaine although the plasma lignocaine levels were
lower with nebulized administration. However, the study
included subjects undergoing rigid bronchoscopy and
all received sedation with intravenous diazepam.[9] With
high-dose background sedation or topical anesthetics,
it may be difficult to interpret the efficacy of individual
components.[10] Gove et al. reported similar acceptability of
the procedure with nebulized lignocaine as compared with
bolus administration and reported that the use of nebulized
lignocaine also avoided additional nasal anesthetic
administration to most participants and recommended
routine use of nebulized lignocaine. However, a high
dose of lignocaine (approximately 400 mg) was used for
nebulization.[11] Lack of patient cooperation to comply with
nebulized lignocaine inhalation technique was mentioned
as the reason of inadequate anesthesia in five participants
receiving nebulized lignocaine. Shorter procedural
duration was reported as an advantage with using
nebulized lignocaine, and authors also mentioned possible
advantages of no-sedation bronchoscopy with use of
topical (nebulized) lignocaine alone without concomitant
diazepam administration because of risks of fall in arterial
oxygenation with use of parenteral diazepam.[11] Keane
et al. demonstrated similar efficacy of nebulized lignocaine
and sprayed lignocaine for pharyngeal anesthesia (similar
cough frequency objectively recorded) and advocated
the nebulized route as participants found the spray
unpleasant. This trial reported the equivalent efficacy
of pharyngeal spray with nebulized lignocaine in the
setting of flexible bronchoscopy performed with sedation
as all participants received intravenous diazepam.[12] This
finding is important as most participants indeed complaint
of a stinging unpleasant sensation on administration of
10% lignocaine spray in clinical practice. In contrast to
the study by Keane and McNicholas, the NEBULA trial
evaluated the role of nebulized lignocaine in addition
to 40-mg pharyngeal spray versus 40-mg pharyngeal
lignocaine spray alone. The NEBULA trial findings
demonstrate that 40-mg pharyngeal (10% lignocaine
spray) administration alone is adequate during no-sedation
bronchoscopy, and when using the same, additional
nebulized lignocaine or a higher 10% spray dose is not
needed. Furthermore, it demonstrates that in this setting
also, a lower concentration of lignocaine (1% lignocaine
solution) administered by spray-as-you-go method can
be used to perform flexible bronchoscopy. Foster and
Hurewitz reported lesser requirements of additional
lignocaine with nebulized lignocaine administration
during “no-sedation” bronchoscopy. However, the
limitation was that the comparator group was saline
placebo without any upfront pharyngeal anesthesia.[13]
The study design of the NEBULA study was similar to
the design by Stolz et al. (150 participants) evaluating the
role of additional nebulized lignocaine over pharyngeal
lignocaine spray administration. Authors demonstrated
the lack of efficacy of additional nebulized lignocaine in
operator- or patient-rated cough/comfort end points, and
importantly, nebulized lignocaine use was not associated
with reduction in total lignocaine dose administered.
These findings are similar with our (NEBULA) study
with the major difference being administration of
combined sedation to all the participants in the study
by Stolz et al.[5] Other differences were two sprays of
10% lignocaine to the pharynx (Stolz et al.) versus four
sprays (NEBULA study) and the use of nasal lignocaine
gel in the NEBULA study instead of lignocaine spray
used by Stolz et al. A RCT has previously demonstrated
lignocaine gel as the preferred method for nasal anesthesia
during bronchoscopy.[14] Therefore, the findings of
NEBULA study are more representative of the prevalent
practice as lignocaine gel is the most commonly used
method for nasal anesthesia during bronchoscopy at
most centers.[15] Charalampidou et al. also demonstrated
lack of benefit of nebulized lignocaine in the setting of
sedation bronchoscopy, but a limitation of this study was
a high baseline lignocaine preparation regimen.[16] All
participants apart from sedation received transtracheal
lignocaine, a high upfront (120 mg of 4% lignocaine) dose
at the vocal cords, and underwent oral bronchoscope
insertion. MacDougall et al. reported no benefit with use
of nebulized lignocaine using a dedicated Enk device
as compared with the conventional spray-as-you-go
method.[17] On the contrary, Dreher et al. demonstrated
reduction in lignocaine and fentanyl doses during
bronchoscopy with nebulized lignocaine using Enk device
as compared with spray-as-you-go method. However, the
study sample size was small (30 participants – 15 in each
arm), and most of the participants received deep sedation
limiting the generalizability of these observations.[18]
Furthermore, authors of this study highlighted the need for
more studies in light sedation or no-sedation bronchoscopy.
The majority of available evidence does not support the
use of nebulized lignocaine during sedation as well as

Madan, et al.: Nebulized lignocaine in bronchoscopy
Lung India • Volume 36 • Issue 4 • July-August 2019 293
Contd...
Table 3: Review of available studies comparing the utility of nebulized lignocaine/nebulized local anesthetic
administration during bronchoscopy
Author, year Number of patients/type of study Intervention End points Sedation/premedication Outcome
KorttilaK
et al.,1981
n=40,RCT Laryngotrachealspraying
(10%sprayfollowedby
4%lignocainesolution)
versusultrasonic
nebulizeradministration
of4%lignocainein
patientsundergoingrigid
bronchoscopy
VASforefcacyof
anesthesiaandVAS
forcooperationof
patients,plasma
lignocainelevels
Intravenousdiazepam
andatropine
premedicationtoall
Bothmodesproduced
adequateanesthesia.
Efcacyoflocal
anesthesiaand
cooperationofpatients
betterafterlignocaine
spray.Amountofmucus,
cumulativelignocaine
dose,diazepamdose,and
postbronchoscopycough
similarbetweentwo
groups.Lowerplasma
lignocainelevelswith
nebulization
GoveRIet al.,
1985
n=52,RCT Threearms
Nebulizedlignocaine
versusnebulized
lignocaineanddiazepam
versus
boluslignocaineand
diazepam
Durationof
procedure,
lignocaineblood
levels,patient
acceptability,
cardiacrhythm
Intravenousdiazepam
andatropine
premedicationtoall
Durationofprocedure
shorterinboththearms
withnebulizedlignocaine,
bloodlevelsoflignocaine
similarinthreegroups,
patientacceptability
similarinthreegroups
KeaneDet al.,
1992
n=54,RCT Nebulized(100mg)2.5‑ml
4%lignocaineversus
sprayedtopical10%(100
mg)lignocaine(+100mg
solutionsprayasyougoin
bothgroups)
Allreceived100mg
lignocainegel
Coughfrequencyon
cassettetape
IVdiazepam+atropineto
allpatients
Nodifferenceinoverall
coughfrequencybetween
groups,sprayunpleasant
FosterWM
et al.,1992
n=38,RCT Nebulizedlignocaine
(threedifferentgroupswith
varyingformulationsto
deliver50mglignocaine)
versussalinenebulization
(fourthgroup)
Additional
lignocaineneeded
forupperairwayand
distalairway
Atropine+codeinetoall
patients
Signicantlyless
additionallignocaine
requirementwith
nebulizedlignocaine
predominantlydueto
lesseramountsrequired
foranesthesiaofpharynx
andlaryngotracheal
regions
SalajkaF
et al.,1999
n=80,RCT 1%trimecaineversus
salinenebulization
Followedbytopical
anesthesiausingsprayas
yougoandlaryngealsyringe
Coughscore,
gaggingepisodes
NA Nostatistically
differencebetween
outcomes
StolzDet al.,
2005
n=150,RCT,double‑blind,
placebo‑controlled
Lignocaine(4mlof4%
lignocaine)versussaline
nebulization
Inadditionto10%
lignocainenasalspray
(4times)andoropharynx
(2times),1%lignocaine
forspray‑as‑you‑go
administration
Supplemental
lignocainedose,
operator‑and
patient‑rated
cough(VAS),
patient‑rated
discomfortscore,
midazolamdoses
Midazolambolusesa
hydrocodone(5mgiv
initially)
Nosignicantdifference
andanyofthe
prespeciedoutcomes
Higherlignocaine
doseadministered
innebulizationarm
(mean±SD‑318±41
versus157±44mg)
Charalampidou
Set al.,2006
n=83
RCT,blinded,placebo‑controlled
Nebulizedlignocaine
(60mg(24patients),
120mg(19patients)
versusplacebo
(40patients)
Transtracheal
lignocaine(4%)120mg,
50mg(5spraysof10%
lignocaine)pharyngeal
spray,120mglignocaine
spraytovocalcords,and
IVdiazepamtoall,oral
routeforbronchoscopy
Easeofprocedure
andcough‑VAS
Sublingualdiazepam+
IVmidazolam±fentanyl
Nodifferenceinease
ofprocedureandcough
VASscoresbetweenthe
threegroups

Madan, et al.: Nebulized lignocaine in bronchoscopy
294 Lung India • Volume 36 • Issue 4 • July-August 2019
no-sedation bronchoscopy. Other practical issues with
routine nebulization include additional infection control
precautions to prevent transmission of infections related
to nebulization, increase in the overall patient preparation
time, and strain on available resources. In high-volume
settings, the major disadvantage with administration of
nebulized lignocaine is that it creates more strain on the
resources required for performing flexible bronchoscopy,
need for a dedicated nebulization area and personnel,
infection control precautions, and requirement of separate
mouthpieces for each patient. Furthermore, some authors
have reported the unpleasant sensation experienced by
participants with nebulized lignocaine administration.[19]
Adverse effects of nebulized lignocaine administration
on airway conductance have also been reported.[20] Most
importantly, as nebulized lignocaine administration does
not lead to improvement in clinically relevant outcomes,
we do not recommend its use. Lignocaine spray is
preferable for pharyngeal anesthesia during bronchoscopy,
and when using it, the use of additional nebulized
lignocaine is not required.
Financial support and sponsorship
Nil.
Conicts of interest
There are no conflicts of interest.
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Table 3: Contd...
Author, year Number of patients/type of study Intervention End points Sedation/premedication Outcome
MacDougallM
et al.,2011
n=50,RCT,nonblinded Nebulizedlignocaine
throughEnkdeviceversus
conventionalinjection
throughworkingchannel
Durationof
procedure,VAS
fortolerability,
easeofprocedure,
frequencyofcough
Midazolamupto0.1mg/
kg±alfentanyl
Nodifferenceinanyend
point
DreherM
et al.,2016
n=30,RCT Lignocainethroughsyringe
throughbronchoscope
workingchannelor
nebulizedlignocaine
Lignocainedose,
sedativedose,
patienttoleranceby
VAS,safety
1.5mgmidazolamand
propofolinall,fentanyl
ifadditionallyrequired
Lowerdoseoffentanyl
andlignocainein
nebulizergroup,no
differenceinpatient
toleranceorsafety
VAS: Visual analog scale, RCT: Randomized controlled trial