Respiration and Sleep Medicine

Section Editor: David Hillman

Alkalinized Lidocaine Preloaded Endotracheal Tube

Cuffs Reduce Emergence Cough After Brief Surgery:
A Prospective Randomized Trial
Papu Nath, MD, FRCPC, Stephan Williams, MD, PhD, Luis Fernando Herrera Méndez, MD, FRCPC,
Nathalie Massicotte, MD, FRCPC, François Girard, MD, FRCPC, and Monique Ruel, RN, CCRP

BACKGROUND: Alkalinized lidocaine in the endotracheal tube (ETT) cuff decreases the inci-
dence of cough and throat pain on emergence after surgery lasting more than 2 hours. However,
alkalinized lidocaine needs 60–120 minutes to cross the ETT cuff membrane; therefore, its
Downloaded from https://journals.lww.com/anesthesia-analgesia by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3iTbq6Fs2NyQZrPOn+vsz3E8z8cnq/A+O7t/zIHz9Vv6tLSGpnO5UXA== on 04/02/2019

usefulness in shorter duration surgery is unknown. This prospective double-blind randomized

controlled trial tested the hypothesis that alkalinized lidocaine would reduce the incidence of
emergence cough after surgeries lasting <120 minutes.
METHODS: After local ethics board approval, American Society of Anesthesiologists I–III patients
consented to be randomized into 1 of 2 groups receiving either alkalinized lidocaine (group AL) or
saline (group S) to inflate the ETT cuff. Cuffs were prefilled >90 minutes before intubation with either
2 mL of 2% lidocaine and 8 mL of 8.4% bicarbonate (group AL) or 10 mL of normal saline (group
S). Cuffs were emptied immediately before intubation. After intubation, either 2 mL of 2% lidocaine
(AL) or 2 mL of saline (S) were injected into the cuff. Additional 8.4% bicarbonate (AL) or saline (S)
was injected into the cuff until there was no air leak. Anesthesia was maintained using desflurane,
rocuronium, and either fentanyl or sufentanil to maintain vital signs within 20% of baseline values.
Opioids administered in prophylaxis of extubation cough were proscribed. A standardized “no touch”
emergence technique was used. A blinded assessor noted any cough above 0.2 minimum alveolar
concentration (MAC) of expired desflurane. At 0.2 MAC, once every 30 seconds, the patient was
instructed to open his eyes and extubation occurred once a directed response was noted.
RESULTS: A total of 213 patients were randomized and 100 patients in each group completed
the experimental protocol. The incidence of extubation cough in group AL was 12%, significantly
lower (1-sided P = .045) than the 22% incidence in group S. The 1-tailed risk ratio for cough in
group AL was 0.55 (0–0.94, P = .045). Total amount of opioids administered (P = .194), ETT
cuff preloading times (P = .259), and extubation times (P = .331) were not significantly different
between groups. The average duration of surgery was 59 ± 28 minutes in group AL and 52 ±
29 minutes in group S (P = .057).
CONCLUSIONS: Alkalinized lidocaine in the ETT cuff significantly decreased general anesthesia
emergence cough after surgeries with an average duration of slightly <1 hour.  (Anesth Analg
2018;126:615–20)

KEY POINTS
• Question: Does filling the cuff of the endotracheal tube with alkalinized lidocaine prevent
emergence cough after surgery lasting <90 minutes?
• Findings: Emergence cough was reduced from 22% in the saline control group to 12% in the
lidocaine-bicarbonate group (P = .045).
• Meaning: Lidocaine-bicarbonate appears to be effective in reducing emergence cough in short
duration surgery.

S
mooth emergence from anesthesia has long been
seen as a method of preventing potential respira-
tory and hemodynamic instability.1,2 Coughing on
From the Département d’anesthésiologie, Centre Hospitalier de l’Université
de Montréal, Hôpital Notre-Dame, Montréal, Quebec, Canada.
Accepted for publication October 10, 2017.
Funding: Department of Anesthesiology, Centre Hospitalier de l’Université
de Montréal, Hôpital Notre-Dame.
The authors declare no conflicts of interest.
Clinical Trials identifier: NCT01715688.
Protocol available at: www.clinicaltrials.gov/ct2/show/study/NCT01715688.
Reprints will not be available from the authors.
Address correspondence to Stephan Williams, MD, PhD, Département
d’anesthésiologie, Centre Hospitalier de l’Université de Montréal, Hôpi-
tal Notre-Dame, 1560 rue Sherbrooke E, Montréal, QC H2L 4M1, Canada.
­Address e-mail to stephan.williams@umontreal.ca.
Copyright © 2017 International Anesthesia Research Society
DOI: 10.1213/ANE.0000000000002647
the endotracheal tube (ETT) during emergence can lead
to undesirable complications such as tachycardia, hyper-
tension, laryngospasm, hypoxemia due to an inability to
ventilate the patient and wound dehiscence.1–5 Multiple
techniques such as deep extubation,1 administration of
intravenous opioids before extubation,6 the “no touch emer-
gence” technique,7 and most recently alkalinized lidocaine
in the ETT cuff8 have been described as effective in reducing
the cough and cardiovascular response associated with the
ETT during emergence.
The use of the ETT cuff as a reservoir for lidocaine to
provide local anesthesia at points of contact with the trachea
was first described in 1990.9 Since then studies have shown
that adding bicarbonate to lidocaine drastically increases
its diffusion across the polyvinyl chloride (PVC) cuff mem-
brane10,11 and decreases the incidence of cough on emer-
gence after surgery lasting more than 2 hours.12,13 Though

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 Lidocaine Preloaded ETT Cuff Reduces Emergence Cough
reduction of emergence cough in surgery lasting <2 hours
is also desirable, the effectiveness of lidocaine-bicarbonate
filled ETT cuffs is unclear. There is debate concerning the
minimal time required for alkalinized lidocaine filled cuffs
to be effective in reducing cough. A small series suggested
that alkalinized lidocaine might be effective for cough
reduction during shorter procedures.8 Conversely, in vitro
data suggest that 30–180 minutes are necessary for alkalin-
ized lidocaine to diffuse across the PVC cuff material,10,11,14,15
and the pharmacodynamic profile of this released lidocaine
on cough incidence is not known. The alkalinized lidocaine
ETT cuff technique, if effective, could be useful in numerous
surgeries of short duration where the association of a rapid
emergence and absence of cough is strongly desired. This
prospective double-blind randomized trial was therefore
designed to test the hypothesis that alkalinized lidocaine
filled ETT cuffs would lower the incidence of cough during
emergence for surgery of <120 minutes duration.
METHODS
This manuscript adheres to the applicable Enhancing the
Quality of Transparency of Health Research (EQUATOR)
guidelines. The study was registered in Clinical Trials.gov on
October 25, 2012 (registration number NCT01715688). After
receiving Centre hospitalier de l’Université de Montréal
ethical and scientific review board approval, 200 American
Society of Anesthesiologists I–III patients provided written
informed consent before being prospectively randomized
(allocation 1:1) between January 2013 and March 2014 using
a computer generated list into 1 of 2 groups receiving either
alkalinized lidocaine (group AL) or saline (S) to inflate the
cuff of their ETT. Patients between the ages of 18 and 80,
scheduled for surgery requiring general anesthesia and endo-
tracheal intubation for a predicted duration of <2 hours were
included in the study. Patients were blinded to their allocation
group. Exclusion criteria included asthma or severe chronic
obstructive pulmonary disease, respiratory tract infection,
preoperative use of cough suppressants, anticipated difficult
intubation, contraindication to lidocaine, pregnancy, airway
surgery, nasotracheal intubation, the inability to provide
informed written consent and patient refusal.
Information about age, weight, height, smoking status,
and the use of angiotensin-converting enzyme inhibitors
was collected. A minimum of 90 minutes before endotra-
cheal intubation, in a preparation room attending to the
operating room, the cuffs of Hi-Lo Mallinckrodt PVC tubes
(Mallinckrodt Company, Juarez, Chihuahua, Mexico) in
group AL were filled with 2 mL of 2% lidocaine and 8 mL of
8.4% bicarbonate (the only commercially available concen-
tration in Canada) while the cuffs in group S were filled with
10 mL of normal saline. The tubes were not removed from
their packaging, packaging that was minimally opened to
gain access to the filling valve, and stored for a maximum
of 24 hours before being discarded. Unlubricated size 7.0
and 8.0 mm ID tracheal tubes were used for women and
men, respectively. Immediately before induction of anesthe-
sia, the 10 mL solution in the cuff was carefully and com-
pletely removed and discarded. The 2 solutions were not
distinguishable by color or viscosity. Standard American
Society of Anesthesiologists monitoring was installed, pre-
oxygenation was achieved with 100% O2 via facemask, and
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general anesthesia was induced using a protocolized tech-
nique which included propofol 1.0–3.0 mg·kg−1, fentanyl
1–3 μg·kg−1, or sufentanil 0.1–0.3 μg·kg−1. The anesthesiolo-
gist, who was blinded to the allocation group, was also per-
mitted to use neuromuscular blocking agents. Laryngoscopy
and endotracheal intubation were performed or supervised
by the attending anesthesiologist. Topicalization with local
anesthetics during laryngoscopy was prohibited. Once the
tube was correctly positioned, a fresh syringe of either 2 mL
of 2% lidocaine (group AL) or 2 mL of saline (group S) was
injected into the ETT cuff. An additional 8 mL of freshly pre-
pared 8.4% bicarbonate (group AL) or 8 mL of saline (group
S) were partially injected into the cuff, until there was no air
leak during positive pressure ventilation with 8–10 mL·kg−1
tidal volumes adjusted to maintain end-tidal CO2 between
33 and 37 mm Hg.
Desflurane between 0.7 and 1.2 MAC in O2 and air for
saturation above 96% was used to maintain anesthesia
until the last suture was in place. The use of crystalloids,
colloids, phenylephrine, ephedrine, and opioid boluses
(fentanyl 0.5–1 μg·kg−1 or sufentanil 0.05–0.1 μg·kg −1) was
permitted to preserve hemodynamic values within 20% of
preoperative baseline. The total amount of opioids adminis-
tered throughout the case including the induction dose was
noted, with sufentanil doses multiplied by a factor of 10 to
calculate fentanyl equivalents for comparison purposes.
The option of a remifentanil perfusion was permitted dur-
ing maintenance of anesthesia, but had to be discontinued
as skin closure began. Opioids administered in prophylaxis
of cough at extubation were proscribed. Actual duration
of surgery was also noted, and surgery was categorized
according to its duration: 0–30, 31–60, 61–90, >90 minutes.
Patients were excluded from the study if surgery lasted
>150 minutes, and another patient was recruited in their
place.
At the end of the procedure, a standardized emergence
technique was prescribed. Neuromuscular blockade was
verified using train of 4 monitoring and antagonized as
necessary using neostigmine and glycopyrrolate. The time
at which desflurane was discontinued and fresh gas flow
was increased to 10 L/min of 100% O2 was noted. A “no
touch emergence technique”7 was used. A blinded asses-
sor noted any cough above 0.2 MAC of expired desflurane
(primary outcome), with further management left to the
anesthesiologist’s discretion. Cough was noted as yes/no
with no attempt to evaluate intensity, frequency, or dura-
tion. When expired desflurane reached 0.2 MAC, once every
30 seconds, the patient was instructed to open his eyes.
Extubation occurred when there was a directed response to
the command and the time was noted.
Statistical Analysis
Statistical analysis was performed with the assistance of
the statistical consultation service of the hospital research
institute (Centre de recherche du Centre hospitalier de
l’Université de Montréal).
The primary outcome—defined as any cough above
0.2 MAC of expired desflurane—was compared between
groups using a 1-sided Fisher exact test. The risk ratio for
cough was also calculated with a 1-sided 95% confidence
interval. A 2-sided Fisher exact test was used to assess if
ANESTHESIA & ANALGESIA
        

there was a difference between the groups on other cat-
egorical variables (ie, the proportion of patients receiving
remifentanil). Continuous variables—including fentanyl
equivalents received, remifentanil dose when administered,
duration of surgery, ETT cuff loading volume, preloading
time and extubation time—were compared using Student t
test. P < .05 was considered to be significant.
If clinically significant differences in preoperative mor-
phometric and demographic data were found, they would
have been addressed by including these variables in a mul-
tivariate model.
Preliminary data collected from our institution with ETT
tubes not filled with alkalinized lidocaine demonstrated an
incidence of cough during emergence of 30%. Given this
baseline incidence, an absolute 15% reduction in cough was
judged by the anesthesiologists in our research group to
represent a clinically relevant reduction. We thus calculated
that a sample size of 95 patients per group (rounded up to
100 for study purposes) was necessary to detect an absolute
15% reduction in cough for the AL group, using a 1-sided
test with 80% power and 5% α error.
RESULTS
The study flowchart is presented in Figure  1. The 2 ran-
domization groups were morphometrically and demo-
graphically similar (Table  1). The total amount of opioids
administered, ETT cuff preloading times, duration of sur-
gery, and extubation times are presented in Table 2. Figure 2
shows the repartition of surgical duration for each group.
The mean duration of surgery was not different between
groups (Table  2; P = .057), and the difference in the pro-
portion of surgeries falling within each 30-minute interval

Figure 1. Patient assessment profile.

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 Lidocaine Preloaded ETT Cuff Reduces Emergence Cough

in Figure 2 was not significant (P = .102). The incidence of risk ratio for cough in group AL was calculated to be 0.55
coughing at extubation (Figure  3) in the alkalinized lido- (0–0.94; P = .045). No patient was reintubated, no ETT cuff
caine group was 12%, significantly lower (1-sided P = .045) perforations were noted, and no major airway trauma or
than the 22% incidence in the saline group. The 1-tailed laryngospasm was noted in either group.

DISCUSSION
Table 1.  Preoperative Demographic and The present study, using a simple preloading technique
Morphometric Patient Characteristics
Group AL Group S
for alkalinized lidocaine in the ETT cuff, demonstrated a
(n = 100) (n = 100) significant reduction in cough on emergence from general
Sex (male/female) 40/60 33/67 anesthesia after short surgical procedures. The effective-
Age (y) 51 ± 14 53 ± 14 ness of alkalinized lidocaine in longer procedures has long
Weight (kg) 76 ± 16 76 ± 17 been established,12 its use in shorter surgeries had previ-
Height (cm) 167 ± 10 166 ± 10 ously been reported in only 1 small series of patients.8 In
Body mass index (kg·m−2) 27 ± 5 28 ± 5
ASA physical status (I/II/III) 18/79/3 32/65/3
the present study, cuff preloading with alkalinized lidocaine
Nonsmokers/smokers 76/24 84/16 before surgery was used to ensure adequate local anesthetic
No ACEI/ACEI 95/5 91/9 diffusion and tracheal topicalization in surgeries whose
Group AL: endotracheal tube cuff filled with alkalinized lidocaine. duration was inferior to the in vitro diffusion time for in-
Group S: endotracheal tube cuff filled with saline. Continuous variables are cuff alkalinized lidocaine. The 12% incidence of cough in
presented as a mean ±1 SD. group AL in the present study is slightly more than the 5%
Abbreviations: ACEI, angiotensin-converting enzyme inhibitors; ASA, American
Society of Anesthesiologists.
cough obtained by Estebe et al8 in their alkalinized lidocaine
group. However, in this study, patients in the saline control
group coughed considerably less than previously reported:
Table 2.  Intraoperative Patient Characteristics 22% vs 70%.8 This difference might be explained by insti-
Group AL Group S tutional differences in the use of intraoperative opioids,
(n = 100) (n = 100) P Value the emergence protocol used in the present study which
Fentanyl equivalents 213 ± 80 199 ± 81 .194 included a modified “no touch” extubation technique7 from
received (μg)
Patients that received 31 34 .763
the moment desflurane anesthesia was discontinued, or the
remifentanil (n) definition of cough in the present study as any cough effort
Remifentanil dose when 54 ± 31 59 ± 81 .485 above 0.2 MAC of expired desflurane. Despite these mea-
administered (μg) sures that reduced the incidence of cough in both the study
Duration of surgery (min) 59 ± 28 52 ± 29 .057 and the control groups in the present study, alkalinized
Volume in endotracheal cuff (mL) 6.9 ± 1.4 6.8 ± 1.3 .702 lidocaine was still effective, and essentially halved the inci-
Preloading time (min) 231 ± 119 213 ± 104 .259
Extubation time (sec)a 513 ± 184 483 ± 2 15 .334
dence of cough in the treatment group. The observed 10%
cough reduction relative to the 22% cough baseline of our
Group AL: endotracheal tube cuff filled with alkalinized lidocaine.
Group S: endotracheal tube cuff filled with saline.
control group is of similar clinical importance to the 15%
Continuous variables are presented as a mean ±1 SD. reduction for a 30% incidence of cough in the control group
a
Calculated from the time of desflurane discontinuation. that was posited when the study was designed.

Figure 2. Number of patients versus

length of procedure by allocation group.
AL indicates alkalinized lidocaine; S,
saline.

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Figure 3. Incidence of emergence cough according to the solution
used for prefilling and filling the endotracheal tube cuff. AL indicates
alkalinized lidocaine; S, saline.
Preloading of ETT tube cuffs before the use of alkalin-
ized lidocaine during short surgical procedures required
a small change in preoperative anesthesia procedures and
very little preparation time. Though the exact time of intu-
bation for each case in an operating room schedule is not
possible to predict, the requirement of at least 90 minutes
prefilling is easy to integrate into clinical practice. The cost
of the lidocaine and bicarbonate used to fill the ETT cuff
were low: 0.17 and 0.31 CAN $ per milliliter of solution,
respectively. Relatively few patients were excluded from the
present study and several different procedures including
gynecological, otolaryngological (not involving the airway),
plastic and general surgery were included, improving gen-
eralizability. Nonetheless, certain limitations apply to our
findings. First, knowing that the anesthetized patient was
enrolled in our study, the medical team might have modi-
fied cough-inducing behaviors (Hawthorne effect), though
this limitation applies to both study groups. Second, the
study was designed to evaluate the prevention of cough at
deeper levels of anesthesia where laryngospasm more often
occurs if extubation is attempted16 and cough only prevents
the efficient evacuation of anesthetic gases, therefore this
study did not examine the incidence of cough at very low
end-tidal concentrations of desflurane when emergence
from anesthesia and extubation usually occurs. The total
time required to extubation was however determined, and
there was no significant difference between groups. Third,
the usefulness of alkalinized lidocaine in the ETT cuff for
very short (<30 minute) procedures cannot be ascertained
from this study. Fourth, our results are statistically fragile:
if only 1 more patient had coughed in the study group, the
resulting differences would not have been judged signifi-
cant, even with the 1-sided testing this study was designed
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for, based on the results of previous studies. This fragility
was also reflected in the wide confidence intervals of the
1-tailed risk ratio for cough, and is the result of the study
design using numbers of patients just sufficient to dem-
onstrate statistical differences greater than the admittedly
arbitrary limit of “significance,” usually defined as P < .05.
When defining the number of patients necessary in each
group in this way, P values very close to .05 will be always
be generated when the actual difference is similar to the
expected difference, as was the case in this study. Finally,
this study shows that prefilling ETT cuffs with alkalinized
lidocaine before using alkalinized lidocaine in the ETT cuff
for short procedures is effective in preventing emergence
cough, but was not designed to show whether prefilling is
necessary. The vagaries of clinical anesthetic practice com-
bined with the requirement in this study for a minimum of
90 minutes prefilling of the ETT with AL resulted in a large
variation in prefilling times. A much larger study would be
required to examine whether shorter versus longer prefill-
ing times influence cough incidence. Given the results of
the present research, an alternative strategy with potentially
greater clinical applicability would be a study that examines
the effectiveness of AL-filled ETT cuffs for short duration
surgery when prefilling is not used. Though in vitro stud-
ies argue against the effectiveness of alkalinized lidocaine in
the ETT cuff without prefilling,10,11 the results of the present
study increase the relevance of this question.
In conclusion, in-cuff alkalinized lidocaine in ETTs pre-
loaded with the same solution before surgery appears to
significantly lower the incidence of emergence cough dur-
ing short surgical procedures. Further studies could cor-
roborate this preliminary finding with a larger number
of patients, examine whether preloading is necessary to
obtain this effect, and whether the same benefit extends to
extremely short (less than 30 minute) procedures. E
DISCLOSURES
Name: Papu Nath, MD, FRCPC.
Contribution: This author helped design the study, conduct the
study, analyze the data, and approved the final manuscript.
Name: Stephan Williams, MD, PhD.
Contribution: This author helped design the study, analyze the
data, and write the manuscript.
Name: Luis Fernando Herrera Méndez, MD, FRCPC.
Contribution: This author helped conduct the study.
Name: Nathalie Massicotte, MD, FRCPC.
Contribution: This author helped design the study, analyze the
data, and write the final manuscript.
Name: François Girard, MD, FRCPC.
Contribution: This author helped design the study.
Name: Monique Ruel, RN, CCRP.
Contribution: This author helped design the study, analyze the
data, and write the manuscript.
This manuscript was handled by: David Hillman, MD.
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