Novel Preoperative Pharmacologic Methods of

Preventing Postoperative Sore Throat due to

Tracheal Intubation
David M. Kalil, CRNA, DNAP
Loraine S. Silvestro, PhD
Paul N. Austin, CRNA, PhD
Postoperative sore throat (POST) is usually self-limiting
but was rated by patients as one of the top 10 most
undesirable anesthetic outcomes. Pharmacologic interventions that have been suggested to decrease the
incidence of POST include application of local anesthetics and corticosteroids to the cuff of the endotracheal
tube. These interventions often require extra steps
during induction of general anesthesia. We sought
evidence for using nonsteroidal, nonlocal anesthetic,
topical pharmacologic interventions conveniently
implemented preoperatively to decrease the incidence
of POST. One hundred seventeen potential evidence
sources were located, with 11 randomized controlled
trials meeting inclusion criteria. The evidence examined ketamine, aspirin, and azulene gargle; benzyda-

ostoperative sore throat (POST) and hoarseness

after general anesthesia with tracheal intubation
occurs in 30% to 70% of patients.1 Postoperative
sore throat, while usually self-limiting, was rated
by patients as one of the top 10 most undesirable
postoperative outcomes.2 The etiology is probably one or
more of the following: mechanical injury during intubation, damage to mucosa due to the pressure from the endotracheal (ET) tube cuff, and dehydration of the mucosa.1
The duration of time a patient stays in the postanesthesia care unit, or potentially the facility, because of
POST increases the cost of care. Patients with POST had
a 14-minute longer stay in the postanesthesia care unit
and a 25-minute longer stay in the ambulatory care unit,
and were discharged 51 minutes later from the facility
compared with those who did not complain of POST.3
Reducing the severity and incidence of POST should
decrease the length of stay and cost of care, and improve
patient satisfaction.
A number of nonpharmacologic factors have been
suggested to increase the incidence of POST, such as inflating the ET tube cuff to more than 20 to 30 cm H2O.4
Use of a laryngeal mask airway rather than ET intubation
may decrease the risk of POST.5 Some have proposed
pharmacologic interventions to decrease the incidence
of POST, including application of local anesthetics1 and

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mine gargle or oral spray; dexpanthenol pastilles; and

lozenges containing amyl-m-cresol or magnesium.
Although there were methodologic concerns with
the studies, the evidence suggested that all the treatment medications decreased the incidence of POST at
early and late intervals. The severity of POST was also
typically reduced. Preoperative ketamine and aspirin
gargle are probably the most promising for providers
practicing in the United States. However, before these
agents are recommended for general use, large multicenter trials should be done exploring not only efficacy
but also dose-response relationships and side effects.
Keywords: Adult, anesthesia, endotracheal intubation,
postoperative sore throat.

corticosteroids6 to the cuff of the ET tube. These interventions often require extra steps during the induction
and intubation sequence.
For this review, we examined the evidence for novel
(nonsteroidal, nonlocal anesthetic) topical pharmacologic interventions conveniently implemented preoperatively that may decrease the incidence of POST in adults.

Materials and Methods

The PICO Question. Evidence-based practice is aimed at
applying the best available current knowledge to improve
decision making in clinical practice.7 Evidence-based
practice requires the clinician to develop a well-designed
PICO question, or patient, intervention, comparison,
and outcome question, that helps to locate pertinent
evidence.8 The PICO question guiding this search for
evidence was: In adult patients requiring ET intubation
(P), what is the efficacy of preoperative administration of
topical nonlocal anesthetic, nonsteroidal pharmacologic
agents (I) in reducing the incidence of POST (O)? All
the evidence addressed these agents, and there was no
comparison intervention in this question.
Search Strategy. The search for evidence (1990 to
2012) was conducted using PubMed, Cumulative Index
to Nursing & Allied Health Literature (CINAHL), and
The Cochrane Database of Systematic Reviews. Search

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terms used alone and in combination included intubation, sore throat, prevention, and postoperative. Inclusion
criteria included evidence pertaining to adults, in full text
form from peer-reviewed journals published in English.
We searched for systematic reviews with or without
meta-analysis and randomized controlled trials. Only
evidence examining nonlocal anesthetic and nonsteroid
pharmacologic treatments administered topically before
intubation was included. Sources examining combinations of drugs or interventions to decrease POST, supraglottic airway use, surgeries involving the oropharynx,
and pediatrics were excluded. Reference lists of the
included evidence were examined for other evidence
sources. This strategy was revised in an ongoing fashion
to optimize the results. The evidence was appraised using
the method described by Melnyk and Fineout-Overholt.7

Results
One hundred seventeen potential evidence sources were
located, with 11 meeting the inclusion criteria (Tables 1
to 3).9-19 Letters to the editor describing studies involving ketamine gargle20 and nebulized magnesium21 were
not evaluated because of a lack of detailed information. All sources9-19 were randomized controlled trials
examining the effectiveness of a nonsteroidal, nonlocal
anesthetic drug administered orally preoperatively to
decrease the incidence of POST due to ET intubation.
Four of the sources examined the effects of ketamine
gargle,9-12 and 3 sources examined benzydamine gargle13
or oral spray.14,15 The other sources investigated azulene
gargle,16 aspirin gargle,13 dexpanthenol pastilles (a dose
of ointment containing the drug),14 licorice gargle,17
lozenges containing amyl-m-cresol,18 and lozenges containing magnesium.19 The authors did not indicate if
gargled solutions were swallowed after gargling. A group
of researchers reported that the investigational drug was
donated by the manufacturer.16
All sources9-19 were from authors practicing outside
the United States. A total of 1,078 subjects participated
in the 11 investigations, with study sample sizes ranging
from 3717 to 378 subjects15 (median sample size, 58). The
sample size in all but 2 studies11,16 was determined using
a power analysis. Subjects withdrew from 6 investigations,9,12,13,15,17,18 and the intention-to-treat principle was
not followed. Even with subject withdrawal, an adequate
number sample size was attained in all but 1 study.9 All
of the studies used blinded observers. Subjects were not
blinded in 3 investigations9,10,17 or were questionably
blinded in 1 study,11 and subject blinding was not reported in another investigation.15 All but 6 groups9-12,18,19
reported that the provider performing the intubation was
blinded. A placebo was used in all the studies except 1.12
Subjects mean age ranged from 24 years9 to 59 years,16
with no significant differences between the control and
treatment groups. Subjects were typically excluded if

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they had a recent sore throat or an upper airway infection. One group of investigators enrolled only female
subjects,13 but the others enrolled both male and female
subjects, and a group did not report subject gender.9
There was no significant difference in gender between
the control and treatment groups in 9 studies.10-12,14-19
Smoking history was either not reported10-13,16-18 or
reported as not being different between the control and
study groups,9,14,15 or potential subjects who smoked
were excluded.19
Subjects typically underwent general, orthopedic,
and gynecologic procedures performed with the subjects
supine, but 1 group enrolled only subjects undergoing
mastectomy,13 another study included only subjects undergoing septorhinoplasty,9 and a third study enrolled
only subjects undergoing lumbar laminectomy with
the subject prone.17 Mean duration of surgery ranged
from 54 minutes9 to 226 minutes,16 with no differences
between control and treatment groups. The mean duration of surgery was not reported in 1 study11only
that there was no difference in this variable between the
control and treatment groups.
Endotracheal intubation was performed solely by an
experienced staff anesthesiologist,9,10,12,16,19 an experienced anesthesiology resident,13,14,17 or an experienced
staff anesthesiologist or an anesthesiology resident.15
In 1 study,18 the anesthesia provider was not identified.
Endotracheal tube size was generally 7.0 to 7.5 mm in
internal diameter for women and 8 to 8.5 mm internal
diameter for men. Intubation attempts were usually
limited to 19-11,15,17,19 or 2 attempts,12,16 but the number
of attempts was sometimes not reported in 3 investigations.13,14,18 The ET tube cuff was usually inflated to
a pressure of 18 to 25 cm H2O, but monitoring of the
pressure varied from not being reported10,18 to being
monitored continuously12,13,17 or every 10,14 30,19 or 60
minutes;15 in the remainder of the investigations, monitoring of cuff pressure was not addressed or described as
intermittent. Nitrous oxide was sometimes used as part
of the gas mixture.10,13,14,19 A heat and moisture exchanger was used by 4 groups of investigators.9,12,13,17 One
group18 reported an oropharyngeal airway was inserted
before extubation on all subjects. Often researchers9-15
reported that care was used when suctioning the posterior pharynx before extubation. Two groups excluded
subjects who coughed or bucked before extubation.10,16
General anesthesia was induced intravenously, and
a nondepolarizing neuromuscular relaxant was administered to facilitate ET intubation in all the studies.9-19
Opioids were often administered intraoperatively, such
as fentanyl (2 g/kg),12 but sometimes intraoperative
opioid administration was described only qualitatively.13
Postoperative opioid dose usually was not reported.
All the investigators9-19 reported the incidence of
POST. All directly asked the subjects about POST rather

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Shrestha et al,11
2010

2009

Rudra et al,10

40

40

40

Canbay et al,9

2008

Evidence
source

Drinking water gargle

(n = 20)

Ketamine 50 mg in
30 mL drinking water
gargled for 30 s, 5 min
before induction of
general anesthesia
(n = 20)

Drinking water gargle

(n = 20)

Ketamine, 50 mg (in 30
mL of drinking water),
gargled for 40 s, 5 min
before induction of
general anesthesia
(n = 20)

Saline gargle (n = 23)

Ketamine, 40 mg (in 30
mL of saline), gargled
for 30 s, 5 min before
induction of general
anesthesia (n =17)

Interventiona
and control

Gender of subjects not reported

8 h: 15 (75)

4 h: 7 (35)
8 h: 6 (30)c
24 h: 3 (15)c

4 h: 15 (75)
8 h: 12 (60)
24 h: 10 (50)

24 h: 12 (60)

8 h: 7 (35)c
24 h: 5 (25)c

4 h: 8 (40)c

All subjects underwent septorhinoplasty

24 h: 6 (35)c

24 h: 14 (61)

4 h: 17 (85)

Power analysis indicated need for 22 subjects per group

4 h: 8 (47)

4 h: 13 (57)

NG, OG, HME, oral airway used; coughing before extubation not reported

ET tube cuff pressure and monitoring not reported

Unable to blind subjects; only mention of observer blinding

Method of sample size determination not reported

Smoking history not reported

N
 o significant differences between groups in gender, weight, or duration of
surgery

Subjects excluded if they coughed or bucked before extubation

NG, OG, or oral airway use not reported

Nitrous oxide used

ET tube cuff pressure monitoring not reported

Smoking history not reported

Unable to blind subjects; only mention of observer blinding

N
 o significant difference in age, height, weight, gender, and duration of surgery
between groups

N
 G, OG, oral airway, ET tube lubrication, HME used; incidence of coughing
before extubation not reported

ET tube cuff pressure monitored intermittently

Unable to blind subjects; only mention of observer blinding

N
 o significant difference between groups in age, height, weight, incidence of
smoking, intraoperative remifentanil, and duration of surgery

3 subjects in treatment group withdrew; intention-to-treat principle not followed

2 h: 8 (47)c

Comments

2 h: 17 (74)

POST
incidence in
treatment
group,b No.
(%)
0 h: 7 (41)c

0 h: 17 (74)

POST
incidence
in control
group,b No.
(%)

than asking general questions about their postoperative

condition. Subjects were usually assessed in the postanesthesia care unit (often indicated as 0 hour) and 2 to
24 hours postoperatively. Severity was usually assessed
using a 4-point visual or verbal analog scale anchored
with 0 as no POST and 3 as severe POST with hoarseness or other voice changes. One group assessed severity
using a 7-point scale16 and another using a 100-point
scale.17 None of the investigators9-19 offered data describing the reliability or validity of the instruments used to
measure POST.

Discussion

Abbreviations: ET, endotracheal; HME, heat and moisture exchanger; NG, nasogastric tube; OG, orogastric tube.
a Investigators indicated that gargled solutions were gargled, not swallowed.
b Hours postoperatively or after extubation.
c P < .05.
d Subject blinding was not likely because of the taste of the ketamine.

Table 1. Randomized Controlled Trials Examining Ketamine Gargle to Prevent Postoperative Sore Throat (POST) Following Endotracheal Intubation

Betamethasone (0.05%)
ointment to ET tube cuff;
no placebo (n = 25)

N
 o significant difference in POST between groups receiving ketamine gargle
and corticosteroid ointment to ET tube cuff

Incidence of coughing before extubation not reported

Subject excluded if > 2 intubation attempts

Oral airway use not reported

HME used

ET tube cuff pressure continuously monitored

Smoking history not reported

N
 o significant differences between groups in age, weight, gender, or duration of
surgery

Only blinding of subjects and observer reportedd

24 h: 12 (48)

2 h: 15 (60)

6 subjects withdrew; intention-to-treat principle not followed

2 h: 6 (24)c
4 h: 5 (20)c
24 h: 1 (4)c

Shaaban &
Kamal,12 2012

50

Ketamine 40 mg (in 30
mL saline) gargled for 60
s, 5 min before induction
of general anesthesia
(n = 25)

4 h: 13 (52)

0 h: 6 (24)c
0 h: 16 (64)

C
 ompared use of corticosteroid ointment applied to ET tube cuff with ketamine
gargle

continued from page 189

The studies reviewed suffered methodologic concerns

to varying degrees, but overall the evidence suggested
all the treatment medications decreased the incidence
of POST at both early (eg, when the subject was in the
postanesthesia care unit) and late (24-hour postoperative) intervals. There were some differences in efficacy
between the medications.
Ketamine Gargle. Four groups9-12 of investigators examined the effect of preoperatively gargling 30
mL of water or saline containing 40 mg9-11 or 50 mg12
of ketamine, an n-methyl-d-aspartate (NMDA) receptor antagonist (see Table 1). This treatment resulted in
probably the most promising results in reducing POST.
The incidence of POST early (in the postanesthesia care
unit) and late (measured at 24 hours) was dramatically
reduced. For example, a group reported that the incidence of POST at 24 hours postoperatively was cut from
48% to 4% (number needed to treat, 3; 95% confidence
interval, 1.5-4.4).12 No authors reported side effects or
systemic effects due to the ketamine.
It is not likely that the results were due to systemic
effects of the ketamine. Subjects (n = 22) gargled 40 mg
of ketamine for 30 seconds, and serum ketamine and norketamine levels were measured for 5 subjects at intervals
up to 103 minutes after gargling.20 The authors reported
that both levels were below those described to produce
analgesia.20 Investigators have suggested that NMDA receptors are found not only in the central nervous system
but also in the peripheral nerves.22,23 Moreover, experimental studies point out that peripherally administered
NMDA receptor antagonists are involved with antinociception22 and anti-inflammatory cascade.23
Benzydamine. Benzydamine is a topical anti-inflammatory with local anesthetic properties. It is widely
available outside the United States. It may act on the
prostaglandin system. It has been used for mucositis due
to radiation treatment. Others reportedly used the drug
to treat lesions due to ET intubation.14
Benzydamine was examined as a 22.5 mg gargle13 and
as an oral spray in 2.16 mg14 and 75 mg15 doses (see Table
2). The higher doses were generally more effective in reducing the incidence of POST. Although the treatment was
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Gulhas et al,14
2007

Agarwal et al,13
2006

Evidence
source

180e

58c

Distilled water sprayed

into mouth (n = 60)

Benzydamine, 4 puffs
(2.16 mg), sprayed into
mouth 30 min and 5
min before induction of
general anesthesia
(n = 60)

Mineral water gargle

(n = 20)

Benzydamine (0.15%),
22.5 mg (in 30 mL of
distilled water), gargled
for 30 s, 5 min before
induction of general
anesthesia (n = 19)

Interventiona
and control
2 subjects withdrew; intention-to-treat principle not followed

N
 o significant difference between groups in age, height, weight, or duration
of surgery

4 h: 3 (16)d
24 h: 0 (0)d

4 h: 10 (50)
24 h: 4 (20)

NG tube not used

6 h: 37 (62)
12 h: 7 (12)d
24 h: 7 (12)d

6 h: 40 (67)
12 h: 14 (23)
24 h: 16 (27)

S
 ignificantly lower incidence of POST in group receiving dexpanthenol
compared with group receiving benzydamine

Suctioned under direct visualization before extubation

Maximum number of intubation attempts not reported

E
 T tube lubrication, oral airway and HME use, and incidence of coughing
before extubation not reported

ET tube cuff pressure monitored every 10 min

10 min: 23 (38)

10 min: 29 (48)

N
 o difference in age, weight, gender, smoking history, or duration of surgery
between groups

Incidence of coughing before extubation not reported

NG, OG, and oral airway use not reported

HME used

ET tube cuff pressure continuously monitored

Maximum number of intubation attempts not reported

ET tube lubricated with water-soluble jelly

Subject blinding not possible; intubator and observer were blinded

Incidence of smoking not reported

All female subjects

2 h: 5 (26)d

2 h: 12 (60)

Comments

0 h: 5 (26)d

POST
incidence in
treatment
group,b No.
(%)

0 h: 16 (80)

POST
incidence
in control
group,b No.
(%)

Abbreviations: ET, endotracheal tube; HME, heat and moisture exchanger; NG, nasogastric tube; OG, orogastric tube.
a Investigators indicated gargled solutions were gargled, not swallowed.
b Hours postoperatively or after extubation.
c An additional 19 subjects were in a group receiving aspirin gargle (data not given here).
d P < .05.
e An additional 60 subjects were in a group receiving dexpanthenol pastilles (data not given here).
f An additional 94 subjects received benzydamine spray to both the oral cavity and ET tube cuff, and another 95 subjects received benzydamine spray to the ET tube cuff and distilled
water spray to the oral cavity (data not given here).

Table 2. Randomized Controlled Trials Examining Benzydamine to Prevent Postoperative Sore Throat (POST) Following Endotracheal Intubation

Suctioned gently before extubation

NG, oral airway, and HME use not reported

ET tube cuff pressure monitored hourly

Incidence of coughing before extubation not reported

Distilled water sprayed
oropharyngeally and to
cuff of ET (n = 95)

24 h: 22 (23)

Subject blinding not reported; intubator and observer blinded

24 h: 10 (11)

4 h: 30 (32)

S
 tatistical adjustments made for age, gender, smoking, and duration of
anesthesia
2 h: 22 (23)

4 h: 12 (13)d

2 h: 38 (40)

0 h: 6 (6)d

Huang et al,15
2010

378f

Benzydamine, 5 puffs
(75 mg), sprayed
oropharyngeally 5 min
before induction of
general anesthesia, and
5 puffs of distilled water
sprayed on ET tube cuff
(n = 94)

0 h: 20 (21)

2 subjects withdrew; intention-to-treat principle not followed

continued from page 191

usually well tolerated, 2 subjects in a study complained of

oral numbing and a distorted sense of taste.13
Azulene. Sodium azulene sulfonate is derived from
azulene, a chamomile extract, and is available in Japan.
Authors there reported that it has an anti-inflammatory
effect and is used to treat chronic gastritis and ulcers.16
They theorized that gargling with sodium azulene sulfonate might be a simple, effective way to prevent POST.
No side effects were reported. These investigators indicated that azulene is absorbed only in the small intestine
and that local tissue reactions are likely rare at the concentration used in the study.
The group from Japan reported significant reduction
of POST immediately postoperatively and at intervals up
to 24 hours after surgery.16 Notably, at 24 hours postoperatively, no subjects reported POST in the treatment
group, whereas 45% of subjects reported POST in the
group receiving the placebo (see Table 3).
Aspirin. Gargling with 30 mL of distilled water containing 350 mg of aspirin was reported to significantly
reduce the incidence of POST while the subject was in
the postanesthesia care unit and at 2 hours, but not at
4 and 24 hours, postoperatively (see Table 3). No side
effects were reported. The widely used anti-inflammatory
has been used in a gargle to relieve pain due to oral
lesions.13
Dexpanthenol. Dexpanthenol applied topically is
reported to have anti-inflammatory properties and acts as
a moisturizer, improving skin hydration.16 Subjects who
preoperatively sucked on pastilles containing 200 mg of
dexpanthenol reported significantly less POST at all intervals up to 24 hours compared with both placebo and
oral benzydamine spray (see Table 3).14 Subjects reported
no side effects. The group theorized a greater positive
effect would have been observed if a larger dose had been
administered (6 rather than 2 pastilles).14 The drug is
marketed for topical but not oral use in the United States.
Licorice. When subjects gargled with 0.5 g of licorice in 30 mL of water, the incidence of POST was significantly reduced at all intervals (see Table 3).17 These
subjects all underwent lumbar laminectomy in the prone
position. No severe side effects were reported. Licorice
contains a number of ingredients. Many of these, including glycyrrhizin, liquilitin, and glabridin, are reported
to have anti-inflammatory and antiallergic properties,
peripheral and central antitussive properties, and ulcerhealing properties, respectively.17
Amyl-m-cresol. Investigators examined the use of a
lozenge containing amyl-m-cresol that is commercially
available only outside the United States as over-thecounter medication (Strepsils, Reckitt Benkiser; see Table
3).18 Fourteen percent of subjects complained of POST
in the postanesthesia care unit compared with 33% of
subjects receiving a placebo (P < .05). A similar reduction was seen 24 hours postoperatively. The lozenges
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40

Ogata et al,16

58d

180e

Agarwal et al,13
2006

Gulhas et al,14
2007

2005

Evidence
source

4 puffs of distilled water

sprayed orally (n = 60)

Dexpanthenol, 2 pastilles
(200 mg), sucked 30
min before induction of
general anesthesia
(n = 60)

Mineral water gargle

(n = 20)

Aspirin, 350 mg (in 30

mL of distilled water),
gargled for 30 s, 5 min
before induction of
general anesthesia
(n = 19)

Tap water gargle (n = 20)

Sodium azulene
sulfonate, 4 mg (in 100
mL of tap water), gargled
for unstated duration and
time before induction of
general anesthesia
(n = 20)

Interventiona
and control
No difference in age, height, weight, gender, or duration of surgery
between groups
Smoking history not reported

4 h: 2 (10)c
24 h: 0 (0)c

4 h: 11 (55)
24 h: 9 (45)

24 h: 7 (12)c

12 h: 14 (23)
24 h: 16 (27)

6 h: 40 (67)

6 h: 22 (37)c
12 h: 5 (8)c

24 h: 1 (5)

24 h: 4 (20)

10 min: 15 (25)c

4 h: 4 (21)

4 h: 10 (50)

10 min: 29 (48)

2 subjects withdrew; intention-to-treat principle not followed

2 h: 5 (26)c

2 h: 12 (60)

Overall, dexpanthenol was more effective than benzydamine in preventing

POST

Suction under direct visualization before extubation

ET tube lubrication, oral airway use, HME use, number of intubation
attempts, incidence of coughing before extubation not reported

NG tube not used

ET tube cuff pressure monitored every 10 min

No difference in height, weight, gender, smoking history, or duration of

surgery between groups

Incidence of coughing before extubation not reported

NG, OG, and oral airway use not reported

HME used

ET tube cuff pressure continuously monitored

Maximum number of intubation attempts not reported

ET tube lubricated with water-soluble jelly

Subject blinding not possible; intubator and observer were blinded

Incidence of smoking not reported

No significant difference between groups in age, height, weight, or duration

of surgery

All subjects were female

0 h: 4 (21)c

0 h: 16 (80)

Study drug was gift from manufacturer

Method of suctioning not reported

Oral airway use and HME method suctioning before extubation not reported

Intermittent monitoring of ET tube cuff pressure

Subject excluded if > 2 intubation attempts, or if coughed or bucked before

extubation

Method for determining sample size not reported

2 h: 8 (40)c

Comments

2 h: 18 (90)

POST
incidence in
treatment
group,b No.
(%)
0 h: 5 (25)c

0 h: 13 (65)

POST
incidence
in control
group,b No.
(%)

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145

70

Ebneshahidi &
Mohseni,18 2010

Borazan et al,19
2012

Placebo lozenge (n = 35)

Lozenge containing
610 mg of magnesium
citrate salt, sucked 30
min before induction of
general anesthesia
(n = 35)

Placebo lozenge (n = 72)

Lozenge containing amylm-cresol, 0.6 mg, sucked

on for 45 min before
induction of general
anesthesia (n = 73)

Water gargle (n = 18)

Licorice, 0.5 g (in 30 mL

of water), gargled for 30
s, 5 min before induction
of general anesthesia
(n = 19)
24 h: 2 (11)c

24 h: 8 (44)

24 h: 3 (9)

2 h: 20 (57)
24 h: 10 (29)

HME and oral airway use, method of suctioning, and incidence in coughing
before extubation not reported

ET tube cuff pressure monitored every 30 min

ET tube lubricated with tap water

No difference in age, weight, gender, duration of laryngoscopy and surgery,

and intraoperative opioid use between groups

2 h: 8 (23)c
4 h: 5 (14)c

4 h: 14 (40)

Subjects with smoking history excluded

0 h: 6 (17)

Oral airway used on all subjects

Smoking history, intubator experience, ET tube lubrication, ET tube cuff

pressure monitoring, intubation attempts, and HME use not reported

No differences in age, height, weight, gender, length of laryngoscopy, and

duration of surgery between groups

5 subjects withdrew; intention-to-treat principle not followed

POST differences with subjects at rest; similar differences on swallowing

POST measured using 100-point VAS

HME used

ET tube cuff pressure continuously monitored

0 h: 16 (46)

24 h: 13 (18)

0 h: 24 (33)

No difference in age, height, weight, gender, or duration of surgery

between groups

4 h: 3 (17)c

4 h: 10 (56)

0 h: 10 (14)c
24 h: 5 (7)c

All subjects underwent lumbar laminectomy in prone position

2 h: 4 (21)c

2 h: 14 (78)

Unable to blind subjects

3 subjects withdrew; intention-to-treat principle not followed

0 h: 4 (21)c

0 h: 13 (72)

Abbreviations: ET, endotracheal; HME, heat and moisture exchanger; NG, nasogastric tube; OG, orogastric tube; VAS, visual analog scale.
a Investigators indicated that gargled solutions were gargled, not swallowed.
b Hours postoperatively or after extubation.
c P < .05.
d An additional 19 subjects were in a group receiving benzydamine (data not given here).
e An additional 60 subjects were in a group receiving benzydamine (data not given here).

Table 3. Randomized Controlled Trials Examining Azulene, Aspirin, Dexpanthenol, Magnesium, and Amyl-m-cresol for Preventing Postoperative Sore
Throat (POST) Following Endotracheal Intubation

37

Agarwal et al,17
2009

continued from page 193

were well tolerated by all subjects. The researchers noted

the lozenges have been used successfully to treat patients
with oral inflammatory diseases and before oral surgery,
and they suggest that amyl-m-cresol produces an antiinflammatory effect.
Magnesium. There was a significantly decreased
incidence of POST when subjects sucked on a lozenge
containing magnesium (Magnesium-Diasporal lozenge,
Med Ila) preoperatively at 2 and 4 hours but not immediately or 24 hours postoperatively (see Table 3).19 Serum
magnesium levels in subjects in the treatment group were
unchanged compared with the control group 4 hours after
surgery. Subjects reported no local or systemic side effects.
The researchers19 indicated that the mechanism of
action of magnesium for reducing inflammation is thought
to be via reducing the release of mediators of inflammation, including histamine, leukotrienes, and thromboxanes. Magnesium may also antagonize NMDA receptors.
They posited that the effect of magnesium was due to
direct contact of magnesium ions with the pharyngeal wall
or that the ions may move directly from the mouth to the
pharyngeal area.
Although the outcome of interest in this review article
was the incidence of POST, the interventions also generally produced a significant decrease in the severity of
POST compared with placebo.9-19 For example, researchers examining preoperative benzydamine oral spray reported that 15% of subjects receiving placebo compared
with 4% of those receiving the study drug reported severe
POST 24 hours postoperatively.15 In another study, the
mean visual analog POST score at all time intervals was
lower for those subjects gargling azulene preoperatively.16 Similar results were noted in studies examining the
other medications.10-14,17-19
The medications were generally well tolerated by
the subjects. Concerns of lozenge use immediately preoperatively in causing a decreased gastric acid pH and
increased volume may be unfounded based on data addressing chewing gum use.24 Use of all the medications
in the manner described by the investigators is probably
best described as an off-label use. Benzydamine, lozenges
containing amyl-m-cresol, azulene, and magnesiumcontaining lozenges are not commercially available in
the United States. The licorice gargle was compounded.
Use of ketamine can be hampered by the additional steps
sometimes needed to document use of the substance.

Summary
Postoperative sore throat, a usually self-limiting complication, continues to be an important concern for the
surgical patient undergoing ET intubation.2 Providers
should closely consider the need for ET intubation.
If it is necessary, steps should be taken to help lessen
the risk of POST. They include avoiding a preoperative
antisialagogue if possible, avoiding trauma during laryn-

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goscopy and intubation, using an appropriate ET tube

size, perhaps lubricating the cuff of the ET tube with a
water-soluble jelly, using the appropriate ET tube cuff
pressure and monitoring the cuff pressure, avoiding the
use of a nasogastric or orogastric tube if possible, carefully suctioning the oropharynx before extubation, and
taking steps to reduce the risk of the patient coughing or
bucking before extubation.4,25
Despite taking these steps, patients may suffer POST.
Local anesthetics1 and corticosteroids6 might be considered to help decrease the incidence of POST. However, an
inexpensive, quick, convenient, and easy-to-administer
medication the patient could take immediately before
induction of general anesthesia to help decrease this
complication is an attractive possibility.
Of the medications found for this review, preoperative
ketamine9-12 and aspirin gargle13 are probably the most
promising for providers practicing in the United States.
However, before these agents are recommended for
general use, large multicenter trials should be done exploring not only efficacy but also dose-response relationships and potential side effects. For example, does aspirin
gargle affect coagulation? For those medications not
available in the United States, studies should continue,
and we should be aware of work being done with these
agents. Hopefully, these drugs will be approved for use
in the United States if found to be safe and efficacious.
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AUTHORS
David M. Kalil, CRNA, DNAP, is an instructor of nurse anesthesia,
Louisiana State University Health Sciences Center School of Nursing, New
Orleans, Louisiana. The author was a student in the Doctorate of Nurse
Anesthesia Practice program at Texas Wesleyan University in Fort Worth,
Texas, at the time this article was written.
Loraine S. Silvestro, PhD, is a professor of pharmacology in the Graduate Programs of Nurse Anesthesia at Texas Wesleyan University.
Paul N. Austin, CRNA, PhD, is a professor in the Doctorate of Nurse
Anesthesia Practice program at Texas Wesleyan University.

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