CLINICAL STUDY
Study on the Effect of Lidocaine in the Cuff for
Endotracheal Tube in Vitro and in Vivo
Biming Zhan, MD, Zhiping Song, MD,y Shibiao Chen, MD,y Jia Min, MD,y and Yang Zhang, MDy
Objective: The purpose of this research was to investigate the
effectiveness on postoperative pharyngalgia of filling the endotra-
cheal catheter (ETC) cuffs with air, double distilled water, 2%
lidocaine hydrochloride, and 1.73% lidocaine carbonate.
Methods: A group of 80 female patients were divided into 4 groups
randomly. The ETC cuffs were filled with air (Group A), double
distilled water (Group B), 2% lidocaine hydrochloride (Group C),
and 1.73% lidocaine carbonate (Group D) after endotracheal
intubation in corresponding patients. Sore throat, hoarseness,
Downloaded from http://journals.lww.com/jcraniofacialsurgery by BhDMf5ePHKbH4TTImqenVHPymkXZPg+V3uteCedqkjUFlSv6KJV2jQ5X5ysC4Cgv on 09/14/2020
bucking, perioperative hemodynamic changes were examined in
all participants.
Results: The Group D had significantly less severity of POST
(P < 0.05), postoperative hoarseness (P < 0.05) and bucking on
emergence from general anesthesia (P < 0.01) than patients from
other groups. The Group D reported significantly less
hemodynamic changes after extubation 1, 5, 10 minutes (P < 0.05).
Conclusion: Lidocaine carbonate injected into the ETC cuffs
decreased the severity of postoperative pharyngalgia,
postoperative hoarseness and bucking on emergence from
general anesthesia.
Key Words: Lidocaine carbonate, postoperative pharyngalgia, the
endotracheal catheter
(J Craniofac Surg 2020;31: 1721–1723)
P ostoperative pharyngalgia (POP) in intubated patients undergo-
ing general anesthesia is one of the most undesirable morbid-
ities and its incidence ranges from 6.6% to 90%.1,2 The etiology of
POP is probably the following: mechanical injury from intubation,
mucosal erosion due to the endotracheal catheter (ETC) cuffs or the
patient bucking and coughing, and dehydration of the mucosa.3 The
size and shape of ETC, the cuff pressure, postoperative vomiting, use
naso-gastric tube during surgery, pre-existing tracheal disease, female
sex, time of the anesthesia, type of surgery are the causal factors of
From the Department of Cardiology, Second Affiliated Hospital of
Nanchang University; and yDepartment of Anesthesiology, First Affili-
ated Hospital of Nanchang University, Nanchang, China.
Received December 16, 2019.
Accepted for publication February 17, 2020.
Address correspondence and reprint requests to Dr. Yang Zhang, MD,
Department of Anesthesiology, First Affiliated Hospital of Nanchang
University, 17 Yong Wai Zheng Street, Nanchang, Jiangxi 330006,
China; E-mail: mzzhangyang@126.com
The authors report no conflicts of interest.
Supplemental digital contents are available for this article. Direct URL
citations appear in the printed text and are provided in the HTML and
PDF versions of this article on the journal’s Web site (www.jcraniofa-
cialsurgery.com).
Copyright # 2020 by Mutaz B. Habal, MD
ISSN: 1049-2275
DOI: 10.1097/SCS.0000000000006469
The Journal of Craniofacial Surgery  Volume 31, Number 6, September 2020
Copyright © 2020 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
POP.4–6 Prevention strategies for decreasing its severity and frequency
can contribute to improve the quality of postanesthesia care.
Prophylactic management for POP includes non-pharmacological
(ETC size or cuff pressure) and pharmacological strategies (local
anesthetics, steroids, or opioids).7 Recent studies indicated that
lidocaine is an effective drug for reducing POP.8 However, alkalin-
ized lidocaine has an advantage with a quicker onset and duration for
preventing POP. So our team devised an experiment to study the
effect of POP with lidocaine hydrochloride and lidocaine carbonate.
Hence, the main purpose of our trial was to determine the
diffusion of low-dose lidocaine hydrochloride and lidocaine car-
bonate across ETC cuffs and compare the different effects of it to
POP. Secondary objectives were patients, tolerance to ETC,
cough, hoarseness.
MATERIALS AND METHODS
Patient Study
This trial was approved by the Ethics Committee of the Second
Affiliated Hospital of Harbin Medical University. Later, we regis-
tered it at the Chinese Clinical Trial Registry (registration number
ChiCTR-TRC-16007857) on January 29, 2016.
A total of 90 experimenters undergoing gynecological laparo-
scopic surgery were included in this research. Experimenters aging
from 18 to 60 were including in our trial, and all patients were ASA I-
II. Then, the following were exclusion criteria: preoperative sore
throat, anticipated difficult intubation, use of succinylcholine, pre-
operative cough, anesthesia with rapid sequence induction (RSI),
Smokers, requiring a nasogastric tube, intubation failed once. After
writing informed consent, patients were randomly divided into four
groups by choosing blinded envelopes: ETC cuffs filled with air
(Group A); ETC cuffs filled with double distilled water (Group B);
ETC cuffs filled with 2% lidocaine hydrochloride(Group C); or ETC
cuffs filled with 1.73% lidocaine carbonate (Group D).
All patients received no premedication. Routine monitoring
(MP60A; Philips, Amsterdam, Netherlands) was performed includ-
ing peripheral oxygen saturation (SpO2), heart rate (HR), endtidal
carbon dioxide, non-invasive arterial pressure (NIAP) and electro-
cardiography (ECG). After establishing IV access and monitors,
induction was accomplished with midazolam 0.04 mg/kg, sufenta-
nil 0.3ug/kg, propofol 2 mg/kg, and vecuronium 0.1 mg/kg. Endo-
tracheal intubation was performed using 7.0 mm internal diameter
ETC (Sheridan, America) for female patients 4 min after vecuro-
nium injection with the same anesthetist, who were blinded to group
allocation. No local anesthetic gel or lubricants were applied on the
ETC cuffs. The cuff pressure in all patients was maintained at
25 cmH2O using a manometer (Feisimei, Shanghai, China).
Mechanical ventilation (Mindray, Shenzhen, China) maintained
end-expiratory partial pressure of CO2 at 35–45 mmHg. We used
an artificial nose to humidify the gas. Maintenance anesthesia
included sevoflurane, remifentanil and vecuronium according to
the operation requirements. After full awakening and recovery,
extubation was performed, and patients were then transferred to
the post anesthesia care unit.
1721
Zhan et al The Journal of Craniofacial Surgery  Volume 31, Number 6, September 2020

A blinded investigator evaluated POP using a 10 cm visual ana-

logue scale (VAS) after extubation (at 30 minute and 2, 6, 12, and
24 hours). Other symptoms that appeared 24 hours after surgery, such
as hoarseness, bucking were systematically evaluated by a modified
4-point scale (1–4): 1, no symptoms; 2, mild; 3, moderate; and 4,
severe. Hemodynamic variables were also recorded before induction
of anesthesia, 1, 5, 10 minutes following extubation. The patients,
anesthetists, surgeons, nurses, and investigators were blinded to group
allotment. This is a randomized, prospective, observer blinded study.

In Vitro Study
We used 40 ETCs (high volume, low pressure, 7.0 mm internal
diameter; Sheridan Teleflex, Reserach Triangle Park, NC) to per-
form an in vitro study. All ETC cuffs were prefilled with 2%
lidocaine hydrochloride (Group a) or 1.73% lidocaine carbonate
(Group b). All ETC cuff pressure was preserved at 25 cm H2O with
continuous measurement using a manometer (Feisimei, Shanghai, FIGURE 1. CONSORT flow diagram of the study.
China). Each ETC was put in an electronic constant temperature
bath of 100 ml double distilled water at 37oC. Then we obtained reported significantly less hemodynamic changes after extubation
samples (1 ml) in the bath at 60, 90, 120, 150, 180, 210, 240 1, 5, 10 minutes (Supplemental Digital Content, Table 4, http://
minutes. Permeation of lidocaine hydrochloride and lidocaine links.lww.com/SCS/B360).
carbonate from ETC cuffs was measured using Reversed-phase
high-performance liquid chromatography (RP-HPLC). In Vitro Study
As time goes on, the concentration of lidocaine carbonate in the
Statistical Analysis bath rose sharply in Group b (Supplemental Digital Content, Table 5,
We calculated the sample size according to previous studies.9–11 http://links.lww.com/SCS/B360). However, lidocaine hydrochloride
The incidence of POP was our primary efficacy variable. We calcu- could not permeate from the ETC cuff at any time, so the lidocaine
lated a sample size that would permit a type I error of a ¼ 5% with a hydrochloride concentration in the bath was none (Supplemental
type II error of b ¼ 5%, and power of 95%. For this, an enrollment of Digital Content, Table 5, http://links.lww.com/SCS/B360).
20 patients per group was required. All statistical analyses were
performed by Statistics Analysis System (SAS), version 9.1.3 (SAS DISCUSSION
Institute, Cary, NC). Student t test was used to assess intergroup The present study demonstrated that lidocaine carbonate injected
differences with a normal distribution, whereas the Wilcoxon Mann- into the ETC cuff could decreased the severity of POP, postopera-
Whitney test was used to assess abnormally distributed data. ANOVA tive hoarseness and bucking on emergence from general anesthesia.
for repeated measurements was used to evaluate data and mixed Furthermore, it was effective in suppressing undesirable hemody-
model statistics using an autoregressive assumption were used for namic changes during extubation. Our in vitro study show that only
outcomes with repeated measures as appropriate. A probability value lidocaine carbonate was able to diffuse.
of less than 5% was considered significant. In the present study, lidocaine hydrochloride had no advantage
over double distilled water when used to inflate the ETC cuff and
RESULTS could injury to patient if the ETC cuff ruptures. In contrast to our
study, Altintas et al12 suggested that lidocaine hydrochloride
Patient Study instilled into the ETC cuff can significantly reduce the incidence
A total of 94 patients were enrolled, 14 were excluded, and then
the remaining 80 patients were randomly divided into 4 groups. The
reasons for the elimination of 14 patients were as follows: intuba-
tion failed once (8), nasogastric tube insertion during the operation
(3) and giving succinylcholine during induction of anesthesia (3)
(Fig. 1). Characteristics of demographic and surgical data are
showed in Supplemental Digital Content, Table 1, http://links.lww.-
com/SCS/B360, and there was no significant intergroup difference
in these variables.
Compared with Group A, B, and C, the severity of POP in group D
was significantly lower (P < 0.05) at postoperative 0.5 hours, 2 hours,
6 hours (Supplemental Digital Content, Table 2, http://links.lww.-
com/SCS/B360). The Group D reported significantly decreased
severity of postoperative hoarseness compared with other groups
(P < 0.05) at postoperative 0.5 hours, 2 hours (P < 0.05) (Supplemen-
tal Digital Content, Table 3, http://links.lww.com/SCS/B360).
The severity of bucking on emergence from general anesthesia
was significantly better in group D compared with group A (1.90
versus 0.55, P < 0.01), B (2.00 versus 0.55, P < 0.01), C (1.95
versus 0.55, P < 0.01) (Fig. 2).
No significant intergroup differences were found between
groups in MAP and HR before induction of anesthesia. Group D FIGURE 2. The severity of bucking on emergence from general anesthesia.

1722 # 2020 Mutaz B. Habal, MD

Copyright © 2020 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
The Journal of Craniofacial Surgery  Volume 31, Number 6, September 2020
and severity of POP, postoperative hoarseness; and maintain hemo-
dynamic stability and tolerance to ETC on emergence from general
anesthesia. What is more, previous study showed that lidocaine
hydrochloride has a low diffusion rate across the ETC cuff.10 An
explanation for this difference may be the following three points:
First, The variable brand and materials of ETC can directly influ-
ence the diffuse of lidocaine hydrochloride; second, the different
methods to measure lidocaine hydrochloride in vitro can also affect
the results; third, differences in solubility and pH of lidocaine
hydrochloride can also affect the experimental results.
Our data showed that intracuff lidocaine carbonate could reduce
hemodynamic fluctuations and coughing to extubation compared
with lidocaine hydrochloride. This was in agreement with the in
vitro study that lidocaine carbonate was able to diffuse across ETC.
Other previous studies9,10 had also found that alkaline lidocaine can
penetrate through the hydrophobic structure of the polyvinyl chlo-
ride (PVC) cuff. endotracheal catheter cuffs are commonly hydro-
phobic chemicals, so the diffusion of lidocaine carbonate through
the membrane of cuff may be similar to that found in the epidural
space.13 Lidocaine has two forms in aqueous solution: ionized
cation and nonionized base. The increasing nonionized base of
lidocaine leads to with a faster onset, duration, and quality of the
nerve blockade.14– 16 Increasing the nonionized base may allow the
diffusion of lidocaine through an ETC cuff more rapidly. An
increase in the pH of lidocaine can increase the percentage of
the nonionized base.14,17–19 Previous studies9,10,20 suggested that
alkalinized lidocaine resulted in 60 times increase in the diffusion
through the ETC cuff which was consistent with our data.
POP is one of the common complications in patients undergoing
general anesthesia with tracheal intubation.1,2 Several pharmaco-
logical methods such as local anesthetics, opioids, anti-inflamma-
tory drugs, or steroids could decrease the incidence and severity of
POP.1,21,22 The characteristics of this trial is that intracuff lidocaine
carbonate was an optimal route for preventing POP which was in
contrast to previous studies.9,20 Lidocaine carbonate may reduce the
severity of POST through its continuous topical anesthetic
effect.23,24 The possible mechanism of the lidocaine effects is that
it can prevent the excitation of airway sensory C fibres25 and reduce
the released sensory neuropeptides followed by neuroplasticity in
the airway and brainstem.26 Mechanical injury from intubation,
mucosal erosion due to the cuff of the endotracheal tube or the
patient bucking and coughing may excite sensory C fibres, which
produce secondary neuroplasticity associated with POP.26
Our present research has some limitations. Firstly, we had not
observe the incidence of POP and postoperative hoarseness. Sec-
ondly, Postoperative follow-up was not long enough in each group.
We had not record them until they were discharged from the
hospital and long term prognosis. Thirdly, Our trial was limited
to patients undergoing gynecological laparoscopic surgery only, So
the results could not be applied to other surgical patients.
In conclusion, we found that lidocaine carbonate injected into
the ETC cuff reduced the severity of POP, postoperative hoarseness
and bucking on emergence from general anesthesia. Furthermore, it
was effective in supressing undesirable hemodynamic changes
during extubation. Our in vitro study show that only lidocaine
carbonate was able to diffuse.
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