ORIGINAL INVESTIGATION
Anesthesia in Flexible Bronchoscopy
Randomized Clinical Trial Comparing the Use of Topical Lidocaine Alone
or in Association With Propofol, Alfentanil, or Midazolam
Andre´ Germano Leite, PhD,*w Roge´rio Gastal Xavier, PhD,z Jose´ da Silva Moreira, PhD,y
and Francisco Wisintainer, MDJ
Downloaded from https://journals.lww.com/bronchology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3Qr4xHpnxR4k74RaA8YrlhCPhi0fg8W2jiKteGuiuBsxGnpIRjbrYig== on 01/08/2019
Abstract: Bronchoscopy is usually performed under topical
anesthesia with or without sedation to promote patient comfort
and the ideal conditions for the physician to perform the
examination. The objective of the study was to establish which
anesthetic protocol used during flexible bronchoscopy (FB) has
the lowest index of complications. This prospective randomized
study analyzed 80 patients undergoing FB. Patients were
randomly assigned to 4 groups of 20 patients each according
to the anesthetic combination used: 200 mg topical lidocaine
(LID group); 200 mg topical lidocaine and 2 mg/kg propofol
(PPF group); 200 mg topical lidocaine and 20 mcg/kg alfentanil
(ALF group); or 200 mg topical lidocaine and 0.05 mg/kg
midazolam (MID group). Scores were assigned to patients
according to the different variables observed during the
endoscopic procedure; the lower the score, the lower the
complication index. Results of the composite score (mean and
SD) for the evaluation of the variables observed during FB were
4.6 ± 3.9 for the PPF group, 7.9 ± 6.6 for the ALF group,
10.0 ± 4.5 for the LID group, and 11.3 ± 5.8 for the MID group
(P = 0.001). Results revealed that the combination of propofol
and topical lidocaine was a superior anesthetic method for FB
than lidocaine alone or in association with midazolam or
alfentanil.
Key Words: bronchoscopy, lidocaine, midazolam, propofol,
alfentanil
(J Bronchol 2008;15:233–239)
Received for Publication March 24, 2008; accepted July 9, 2008.
From the *Post Graduate Program in Pneumology, Universidade
Federal do Rio Grande do Sul (UFRGS); zSchool of Medicine;
ySchool of Medicine, Fundac¸ão Faculdade Federal de Ciências
Médicas de Porto Alegre (FFFCMPA) and, Universidade Federal
do Rio Grande do Sul (UFRGS), Porto Alegre; wEthics in Research
Committee, Pompéia Hospital; and JDe Vita Oncology and Hemato-
logy Institute, Caxias do Sul, Brazil.
There are no real or potential conflicts of interest related to the authors
of this manuscript.
This study was conducted as a requirement for the Doctor’s Degree in
Pneumonology at Universidade Federal do Rio Grande do Sul.
Reprints: André Germano Leite, PhD, Rua Gal, Arcy da Rocha
Nóbrega, 401/303, CEP 95040-000, Caxias do Sul, RS, Brazil (e-mail:
andregermanoleite@gmail.com).
Copyright r 2008 by Lippincott Williams & Wilkins
J Bronchol  Volume 15, Number 4, October 2008
F lexible bronchoscopy (FB) is a routine procedure
performed by pulmonologists. This procedure induces
different degrees of nerve stimulation, particularly the
cough reflex, which may complicate the performance of
the examination. Repeated stimulation of cough reflex is
not tolerated by patients, who frequently try to expel the
bronchoscope from the airways. Therefore, patients often
need to repeat the examination, which should also be
taken into consideration when planning an endoscopic
procedure that does not cause significant discomfort to
the patient.
In addition to its low risk, bronchoscopy has a very
favorable risk/benefit ratio. The incidence of complica-
tions ranges from 0.08% to 9%, and mortality, from
0.01% to 0.1%.1–3 Premedication and the use of topical
anesthesia does contribute to these complications. In a
study by Credle et al,4 these drugs were responsible for 11
of the 22 significant complications. Although infrequent,
complications do exist, and physicians performing the
procedure should be able to identify and rectify them
immediately.
This procedure is usually performed under topical
administration of anesthesia to the airways, with or
without sedation. The sedative drugs of choice are opioids
and benzodiazepines, either alone or in combination with
other drugs. Studies have reported conflicting results
related to the beneficial effects of benzodiazepines
on patient’s tolerance to undergo FB.5–8 Midazolam is
the sedative of choice for most physicians performing
FB.9 Lidocaine is the anesthetic most frequently used
during FB.10
Although a large number of anesthetics have been
used in airway surgeries, short-acting anesthetics have
played an increasingly important role in the safe
performance of procedures and rapid patient recov-
ery.11,12 Such drugs have enabled the performance of
outpatient bronchoscopy.10 Rapid regain of alertness, as
well as recovery of the airway protective reflexes and
muscular contractility are fundamental, especially in
patients with respiratory disorders.
The objective of this study was to establish which
anesthesia protocol used during FB has the lowest index
of complications.
233
Leite et al
PATIENTS AND METHODS
This is a prospective double-blinded clinical trial
comparing 4 different anesthetic regimens for sedation
during FB.
The patients included in this study were referred for
FB for suspected bronchogenic carcinoma. The diagnos-
tic procedures included endobronchial biopsy and
bronchoalveolar lavage. Bronchoscopy time was limited
to 15 minutes. The time limit of 15 minutes was
established for bronchoscopic procedure to avoid multi-
ple doses administration of anesthetic drugs. The
objective of this study was not determining the accuracy
of FB in lung cancer diagnosis. It is very important to
point out that the time limit of 15 minutes was the only
inclusion criteria used for study. Procedures where
anticipated duration was more than 15 minutes were
excluded from the study (ie, therapeutic procedures,
transbronchial biopsy). All procedures were performed
by a single bronchoscopist.
Patients included in the study were classified
according to the anesthesia risk classification of the
American Society of Anesthesiologists (ASA) as class I,
II, and III.
Patients were randomly assigned to 4 groups,
described below:
Lidocaine (LID) group: only topical anesthetic (200 mg
lidocaine).13
Propofol (PPF) group: topical anesthetic (200 mg
lidocaine) and intravenous (IV) administration of
propofol (2.0 mg/kg),12,14 1 mg/kg at induction, and
0.5 mg/kg at 5 and 10 minutes after induction.
Alfentanil (ALF) group: topical anesthetic (200 mg
lidocaine) and IV bolus administration of alfentanil
(20 mg/kg).10
Midazolam (MID) group: topical anesthetic (200 mg
lidocaine) and IV administration of midazolam
(0.05 mg/kg).10
All patients received 100% oxygen supplementation
via mask immediately before the bronchoscopic proce-
dure for 2 minutes, followed by oxygen at 3 L/min
throughout the procedure via nasopharyngeal tube
previously inserted through the patient’s nostril.
Lidocaine gel was applied to the nostril used for the
procedure; lidocaine solution was also administered
through the cricothyroid membrane puncture.15 Total
initial topical anesthetic volume was 20 mL of 1%
lidocaine (200 mg) per patient. Additional doses of topical
anesthetic were administered when requested by the
bronchoscopist to inhibit cough reflex. Total dose did
not exceed 5 mg/kg.10 The additional lidocaine dose was
included in the evaluation of the performance of each
anesthetic modality.
Patients were evaluated according to different
variables. Each variable was analyzed independently
and patients were assigned a score for each variable,
and together they made up a composite score: the greater
the score, the greater the magnitude of the event and,
consequently, the greater the intensity of the complica-
234
J Bronchol  Volume 15, Number 4, October 2008
tion. The scoring system was developed according to
severity and intensity of side effects observed during
the bronchoscopic procedure. The lower score was 0,
corresponding to absence of side effects and the maximum
score was 6, corresponding to change of initial anesthetic
modality (failure of the method). The different grades of
the variables were adjusted according to statistical
analysis. The composite score and all its components
were described according to mean and SD (Table 1). An
intergroup comparison was made through analysis of
variance 1-way test, under composite scores ranks, with
statistically significant differences localization by Duncan
post-hoc test. The Kolmogorov-Smirnov did not reject
the Gauss curve as approximation model of scores
distribution. The approach was adopted according to
literature argumentation.16,17 This study was submitted to
analysis and epidemiologic specialists of the Universidade
de Sao Paulo and Universidade Federal do Rio Grande
do Sul.
Demographic data were described as mean and SD
for the age and as frequency and percentages for sex.
This study was approved by the Research Ethics
Committee of our institution. All the patients included in
the series were provided with preinformed consent.
RESULTS
Eighty-nine patients were selected for the study.
Nine were excluded: 4 had an ASA IV classification of
anesthesiology risk, 3 had a procedure that lasted longer
than 15 minutes, 1 patient had an indication of
therapeutic bronchoscopy (hemoptysis), and 1 patient
had cardiac arrhythmia detected at admission. Eighty
patients were randomly assigned to 4 groups: 20 patients
in the PPF group, 20 in the ALF group, 20 in the LID
group, and 20 in the MID group. The power was 85% for
a difference between groups of the 0.5 and a SD of 0.5 in a
2-sided analysis.
Demographic data are shown in Table 2. All
patients included in the study were white.
Duration of Bronchoscopic Procedure
Mean duration of bronchoscopic procedure was
12.8 ± 2.8 minutes for the PPF group, 14.2 ± 1.4 minutes
for the ALF group, 13.2 ± 2.1 minutes for the LID
group, and 14.0 ± 1.9 minutes for the MID group,
excluding the duration of interruptions (P = 0.128).
Need to Change the Anesthetic Modality
Initially Planned
Only 6 cases required the change of the anesthetic
modality initially planned: 3 patients in the LID group
(2 due to psychomotor agitation and 1 due to cough) and
3 in the MID group (2 due to cough and 1 due to
psychomotor agitation).
Table 3 shows the comparison of the variables that
made up the composite score for the evaluation of events
observed during FB, distributed according to PPF, ALF,
LID, and MID groups.
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J Bronchol  Volume 15, Number 4, October 2008 Anesthesia in Flexible Bronchoscopy

TABLE 1. Composite Score for the Evaluation of Inconvenient TABLE 2. Demographic Characteristics of Study Groups
Events Observed During Bronchoscopy PPF ALF LID MID
Criteria Scores Variable n = 20 n = 20 n = 20 n = 20 P
Arrhythmia Age, y 58.3 ± 13.8 54.6 ± 14.3 60.3 ± 12.7 54.1 ± 20.3 0.533
Absent 0 Male sex 14 (70.0) 17 (85.0) 12 (60.0) 15 (75.0) 0.353
Without hemodynamic alterations 1 (%)
With hemodynamic alterations 4
Data presented as mean ± SD and frequency (%).
Hypoxemia
ALF indicates alfentanil; LID, lidocaine; MID, midazolam; PPF, propofol.
Absent 0
Mild (SaO2 85%-89%) 1
Moderate (SaO2 70%-84%) 2
Severe (SaO2 <70%) 4
Additional lidocaine
Not necessary 0 group had the lowest scores. In comparison with the other
Dose up to 100 mg 2 groups (LID, MID, and ALF), the quantification and
Dose >100 mg 4 qualification of events were less intense according to the
Change of modality
Without change in initial modality 0
classification system used. The PPF group was followed
With change in initial modality 6 by the ALF group, which did not show any statistically
Cough significant difference from the LID group. The fourth and
Absent 0 last group was MID, which did not show any statistically
Sporadic, no interruption of procedure 1 significant difference from the LID group (Fig. 1).
Mild, short interruptions in the procedure 2
Moderate, additional use of topical anesthetic drug 4 Although we did not identify a statistically sig-
Intense, determines change of modality 6 nificant difference between elderly and younger adult
Psychomotor agitation patients, the recommendation of lower propofol dosage
Absent 0 requirements in elderly patients18 could be asset to
Verbal request to take out the bronchoscope 2
Head movement to take out the bronchoscope 4
pharmacokinetic rather than pharmacodynamic differ-
Determines change of modality 6 ences. Therefore, lower induction doses should be kept in
Nausea, vomiting use for geriatric patients.18
Absent 0
Present 1
Respiratory depression
Absent 0
DISCUSSION
Apnea—mask ventilation 4 The usual responses to FB are an increase in cardiac
Apnea—orotracheal intubation 6 work and in blood pressure, together with episodes of
Bronchospasm hemoglobin desaturation.19,20
Absent 0
Present 3
The responses are associated with changes in partial
Laryngospasm oxygen pressure (PaO2), partial carbon dioxide pressure,
Absent 0 and cardiac output. Application of suction through the
Present 4 working channel of the bronchoscope should be restricted
Lidocaine intoxication to a shorter time interval in these patients to avoid
Absent 0
Seizures 4 significant changes in the ventilation/perfusion ratio
Arterial hypotension* (V/Q). These changes may lead to a substantial increase in
Absent 0 the risk of arrhythmia21 and myocardial ischemia during
Mild (MAP fall 20%-30%) 1 FB.22 Another factor in the genesis of arrhythmia in FB is
Moderate (MAP fall 31%-40%) 2
Severe (MAP fall >40%) 4
the vagal response secondary to the insertion of the
Level of consciousnessw bronchoscope in the airway, which may determine the
Glasgow 15 0 occurrence of bradycardia.
Glasgow 14 1 This study did not find statistically significant
Glasgow 13 2 differences in the occurrence of arrhythmias between the
Glasgow <13 3
study groups (P = 0.376).
*MAP measured immediately before and 2 min after the beginning of broncho- Bradycardia may occur immediately after the IV
scopy. administration of alfentanil.23 Although the use of
wMeasured 15 min after end of bronchoscopy.
MAP indicates mean arterial blood pressure; SaO2, hemoglobin oxygen propofol has been associated with bradycardia, this study
saturation. did not observe bradycardia in the group of patients that
received the drug. The mechanism by which propofol
causes the bradycardia has not been well established.
Table 4 shows the results of the composite score in Ozturk et al24 reported that the occurrence of arrhythmia
the evaluation of events observed during bronchoscopy was significantly greater in the midazolam group than in
according to the different groups. the propofol group in their study.
The comparison of composite scores in the evalua- The score found in our study did not show any
tion of events observed during FB indicated that the PPF significant differences in the occurrence of hypoxemia

r 2008 Lippincott Williams & Wilkins 235

Leite et al J Bronchol  Volume 15, Number 4, October 2008

TABLE 3. Variables for Inconvenient Events Analyzed During Bronchoscopic Procedures

PPF ALF LID MID
Score Components n = 20 n = 20 n = 20 n = 20 P
Dysrhythmia (0-4) 0.3 ± 0.4 0.6 ± 0.9 0.4 ± 0.5 0.3 ± 0.4 0.376
Hypoxemia (0-4) 0.7 ± 1.1 1.1 ± 1.3 0.5 ± 0.8 1.3 ± 1.4 0.117
Coughing (0-6) 1.9 ± 1.6a 1.7 ± 1.9a 3.4 ± 1.1b 3.0 ± 1.8b 0.003
Additional lidocaine (0-4) 0.6 ± 0.9 0.8 ± 1.0 1.3 ± 1.0 1.3 ± 1.0 0.054
Lidocaine intoxication (0-4) 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 —
Restlessness (0–6) 0.3 ± 1.0a 1.6 ± 1.5b 3.3 ± 1.5c 1.6 ± 1.9b <0.001
Respiratory depression (0-6) 0.2 ± 0.9 0.6 ± 1.5 0.0 ± 0.0 0.8 ± 1.6 0.138
Bronchospasm and/or 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 —
laryngospasm (0-1)
Hypotension (0-4) 0.2 ± 0.4 0.5 ± 0.9 0.1 ± 0.3 0.3 ± 0.4 0.287
Dizziness and/or vomiting (0-1) 0.0 ± 0.0 0.0 ± 0.0 0.1 ± 0.3 0.0 ± 0.0 0.106
Level of consciousness (0-3) 0.5 ± 0.9a 1.2 ± 0.9b 0.0 ± 0.0a 1.7 ± 1.2c <0.001
Change of initial method (0-6) 0.0 ± 0.0 0.0 ± 0.0 0.9 ± 2.2 0.9 ± 2.2 0.091
Different superscript letters indicate significant differences (Duncan post-hoc test).
ALF indicates alfentanil; LID, lidocaine; MID, midazolam; PPF, propofol.

between the study groups (P = 0.117). All FB determines The use of low or moderate doses of sedation with
some degree of deleterious effects on respiratory physio- midazolam also did not change the probability of a
logy.10 The usual and expected response in bronchoscopy decrease in SaO2 in the study conducted by Jones and
is a decrease in hemoglobin oxygen saturation (SaO2).19,20 O’Driscoll.33
Schnapf25 reported a decrease in SaO2 to below 5% of Cartwright et al34 showed that alfentanil reduced
baseline in 80% of the cases studied, particularly when acute ventilatory response to hypoxia.
the bronchoscope was placed in the middle of the trachea. The PPF and ALF groups in our study had
The causes of hypoxemia have been assigned to the significantly lower scores for the variable ‘‘cough’’ than the
procedure itself19,26 or to respiratory depression second- LID and MID groups (P = 0.003).
ary to the use of sedation.27 Cough is a complex reflex that initiates with the
Matsushima et al28 and Neuhaus et al29 showed that stimulation of receptors in the respiratory system. These
patients had a decrease in forced expiratory volume in 1
second and an increase in the residual functional capacity
during the performance of FB.
Albertini et al30 reported that the decrease of PaO2
secondary to FB may be avoided in many patients by
the use of a Venturi mask at 40% during and after the
procedure. Different techniques may be used to ventilate
the patient or to provide oxygen during the performance
of rigid or FB: spontaneous respiration, intermittent
positive pressure ventilation, use of the Sanders injection
system, and ventilation with high-frequency jets.31 Anto-
nelli et al32 studied the use of noninvasive positive
pressure ventilation via facemask in immunosuppressed
patients with abnormal gas exchange and recommended
its use during FB.

TABLE 4. Comparison of Composite Scores of Evaluation of

Events Observed During Bronchoscopy
PPF ALF LID MID
n = 20 n = 20 n = 20 N = 20 P
a b b,c c
Composite 4.6 ± 3.9 7.9 ± 6.6 10.0 ± 4.5 11.3 ± 5.8 0.001
score
FIGURE 1. Comparison of composite scores for the evaluation
Data presented as mean ± SD. Different superscript letters indicate statisti-
cally significant differences (Duncan post-hoc test). of inconvenient events observed during bronchoscopy (Dun-
ALF indicates alfentanil; LID, lidocaine; MID, midazolam; PPF, propofol. can post-hoc test). ALF indicates alfentanil; LID, lidocaine; MID,
midazolam; PPF, propofol.

236 r 2008 Lippincott Williams & Wilkins

J Bronchol  Volume 15, Number 4, October 2008
receptors may be sensible to touch and mobili-
zation (mechanic receptors) or primarily sensible
to toxic gases (chemical receptors).35 The occurrence of
cough during bronchoscopy is the rule. The direct
stimulation of mechanical receptors triggers the cough
reflex.
Different techniques are used for the application
of local anesthetics in the airways, and their purpose is to
inhibit the laryngeal and cough reflexes.10
The analgesic and cough suppressant properties of
opioids are well known.23
Greig et al9 demonstrated that alfentanil is a more
effective antitussive agent than midazolam for out-
patient FB.
The absorption of local anesthesia through the
oropharyngeal mucosa is relatively low, but its absorp-
tion through the lower airways may be quite significant.
The estimation of the amount of local anesthesia that
is absorbed after its administration in the airway may be
inaccurate. The maximal dose recommended for the
administration of topical lidocaine is 5 to 8 mg/kg.10
Complications caused by the use of topical anes-
thesia are frequently the result of a large dose of the
drug.33,36,37 Signs and symptoms of neuroexcitation, such
as dizziness and audiovisual disturbances, are indications
of intoxication by lidocaine and usually precede more
serious complications, such as seizures, coma, and
cardiovascular collapse.10
No significant differences were found in psycho-
motor agitation between the MID and ALF groups, but
a significant difference was found between LED and PPF,
LED and ALF, LED and MID, MID and PPF, and PPF
and ALF (P<0.001).
Clarkson et al38 reported that propofol has a
sedative effect similar to that of midazolam, but its action
was more rapid both in the onset of action and in the
return to initial consciousness levels. Although respira-
tory depression may be a frequent complication in
bronchoscopy,10 it was not significant in our study
groups. Although benzodiazepines cause less respiratory
depression than opioids,38,39 no significant difference was
found between the different groups in our study
(P = 0.138). Peacock et al40 found that local anesthesia
may be responsible for prolonged respiratory depression
in patients who undergo bronchoscopy. High doses of
alfentanil or midazolam may produce respiratory depres-
sion and apnea, although the same may occur with lower
doses.22
The combination of amnesia and antianxiety
effect of benzodiazepines with the analgesic and cough
suppressant effect of opioids may be beneficial,
although their synergetic action increases the risk of
cardiovascular and respiratory complications.2 Randell
and Lindgren41 found a decrease in respiratory
rate with the use of fentanyl (1 mcg/kg) and diazepam
(0.05 mg/kg) in the sedation of patients who underwent
FB.
No case of bronchospasms or laryngospasms was
observed in any of the cases included in this study.
r 2008 Lippincott Williams & Wilkins
Anesthesia in Flexible Bronchoscopy
No significant differences in the occurrence of
arterial hypotension were found between any of our
groups (P = 0.287). McRae10 demonstrated that anes-
thetic induction with propofol provides hemodynamic
stability in patients who undergo bronchoscopy.
Yamaguchi et al14 demonstrated that the association
of propofol and fentanyl may prevent the occurrence of
hemodynamic instability during bronchoscopy. Accord-
ing to Matot et al,42 the association of propofol and
alfentanil reduces the occurrence of arterial hypotension
but does not prevent myocardial ischemia.
Uetsuki et al43 did not find significant differences in
arterial blood pressure, heart rate, respiratory rate, or
levels of SaO2 in the comparison of patient groups of
different ages who underwent anesthesia with propofol
for bronchoscopy.
We also did not find any significant differences
in the occurrence of nausea or vomiting between our study
groups (P = 0.106).
Although the role of propofol in the management of
postoperative nausea and vomiting is not well established,
Gan et al44 reported that propofol was effective in their
management.
No statistically significant differences were found
between the PPF and LID groups. These groups,
however, had significantly lower scores for the variable
‘‘consciousness level’’ than the ALF and MID groups.
The scores for the ALF group were significantly lower
than those for the MID group (P<0.001). Clarkson
et al38 conducted a comparative study of propofol
(mean induction dose = 104.7 mg; mean maintenance
dose = 121.9 mg) and midazolam (mean induction
dose = 9.3 mg; mean maintenance dose = 3.7 mg). Con-
sciousness level was more rapidly recovered with the use
of propofol (2.3 vs.6.3 min; P<0.01). Crawford et al45
also showed that the recovery after sedation was faster in
patients who received propofol during FB than in patients
who received midazolam.
Hypnotic sedative drugs not only increase sedation,
but also decrease the level of memory as their serum
concentration increases.46
The administration of alfentanil in the prescribed
dose does not provide, according to some authors,22,47
adequate levels of sedation.
Our results showed that in only 6 cases was it
necessary to change the anesthetic method initially
planned, and the causes were discussed above in the
analysis of the variables cough and psychomotor
agitation.
The low incidence of collateral effects and accidents
associated with anesthesia, together with the reduced
hemodynamic depression and a short recovery time, also
made Mesiti et al48 recommend the use of propofol to
anesthetize patients who undergo FB.
Randell49 reported that the use of propofol in
addition to topical lidocaine provides better conditions
for the performance of FB than other methods.
Despite the number of the collateral effects to have
been small, it was possible to detect significant differences
237
Leite et al
between the studied groups. This means that propofol
demonstrated lower intensity of adverse effects than other
tested drugs in accordance with the evaluation system
adopted.
CONCLUSIONS
A comparison of composite scores was made for the
evaluation of inconvenient events with usual intravenous
anesthetic drugs for FB. Four groups of patients were
individualized: with only topical lidocaine employed (I)
and topical lidocaine plus propofol (II), fentanil (III) and
midazolan (IV), each drug delivered as the sole intrave-
nous anesthetic prescription. The group treated with
intravenous propofol (II) had the lowest inconvenience
scores followed by intravenous alfentanil (III). But
alfentanil (III) and midazolan (IV) groups did not show
statistically significant differences from patients taking
only topical lidocaine (I) but did to the propofol one (II).
This study is an attempt to qualify available intra-
venous anesthetic drugs toward its appropriate use in
sedation for patient comfort and safety during FB
procedures.
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