JOURNAL CLUB: EFFECT ON

POSTOPERATIVE SORE THROAT OF SPRAYING THE ENDOTRACHEAL

TUBE CUFF WITH BENZYDAMINE

HYDROCHLORIDE, 10% LIDOCAINE, 2%

LIDOCAINE

นศ.พ. ณั�ฏฐิ�ณัพรชำ� น ญเวชำ 50192205นศ.พ. ธั�ญญ พร นนทภ 50192234

POST OPERATIVE SORE THROAT(POST)

POST

บ ดเจ็�บของ

เน��อเยื่��อในชำ!อง

ป กและคอใส่!ส่ ยื่

ยื่ งท งจ็มู*ก

ด*ดเส่มูหะ

กระบวนก รส่อดผ่! น

ท!อชำ!วยื่ห ยื่ใจ็

ชำน�ดและแรงกดท�บของ

cuff ท�มูต่!อผ่น�ง

หลอดลมู

ก รกดท�บของท!อชำ!วยื่ห ยื่ใจ็ก�บส่ ยื่เส่ยื่ง

BENZYDAMINE HYDROCHLORI

DE

Benzydamine HydrochloridePharmacodynamics

benzydamine inhibits the biosynthesis of prostaglandins under certain conditions, but its properties in this respect have not been fully elucidated

Absorption

Benzydamine is well absorbed following oral administration, benzydamine is well absorbed into the inflamed oral mucosa where it exerts anti-inflammatory and local anaesthetic actions. Plasma benzydamine levels following use of benzydamine orally are low

Excretion Metabolism is largely by oxidative pathways, although dealkylation and excreted largely in the urine.

Most of the absorbed dose was eliminated in the 1st 24 hrs. Repeated administration for 7 days did not result in accumulation of benzydamine in plasma

Benzydamine HydrochlorideIndications Listed in Dosage

Dosage

Adult: Topical Painful musculoskeletal and soft tissue disorders As 3-5% cream (as HCl) or 6% cream/spray (as salicylate): Apply as directed. Pain or irritation of the mouth and throatAs 0.15% soln: As HCl: Gargle 15 mL 1-3 hrly for not >7 days. Child: 6-12 yr: 4 puffs every 1.5-3 hr.Topical/CutaneousPain and inflammation associated with musculoskeletal and joint disordersAdult: Apply a 3-5% cream. As salicylate: Apply a 6% cream/spray on the skin. Use as instructed.

overdosage May lead to hallucinationConraindications Hypersensitivity.

Adverse Drug Reactions

Topical: Erythema, rash, photosensitivity. Mouth/throat preparations: Numbness or stinging sensation of oral mucosa

MIMS class

Non-steroidal antiinflammatory drugs (NSAIDs)/ Preperation for vaginal condition / Mouth/throat prepaeration

Benzydamine Hydrochloride

Difflam® 0.15 % w/v Thai FDA category : D

Comfflam® (Taiwan)

Comfflam 1.5 mg/1 mL x 25 mL, Comfflam 1.5 mg/1 mL x 30 mL

Indication

Painful & inflammatory conditions of the mouth & throat e.g. tonsilitis, sore throat, radiation mucositis, aphtous ulcer, post-orosurgical & periodontal procedures

Dose

Adult & children > 12 years 4-8 sprays onto the affected area, children 6-12 years 4 sprays onto the affected area. May be repeated every 1.5-3 hrly. Duration should not exceed 7 days.

Special precaution

Hepatic or renal impairment. Pregnancy, children < 6 years.

Adverse drug reaction

Oral numbness, dryness or thirst, tingling, warm feeling in mouth, altered sense of taste.

LIDOCAINE

LIDOCAINE

Lidocaine

blockade of voltage-gated sodium channels

excitable membrane of nerve axons

maintains a resting transmembrane potential of 90 to –60 mV

Inhibit action potential inhibit nerve impulse

LIDOCAIN

E

LIDOCAINE

LIDOCAINE Table 26–1 Structure and Properties of

Some Ester and Amide Local Anesthetics.1

Structure Potency (Procaine =

1)

Duration of Action

EstersCocaine Procaine(Novocain) Tetracaine(Pontocaine)Benzocaine

2 1

16

 MediumShort Long

Surface use only

 AmidesLidocaine (Xylocaine) Mepivacaine (Carbocaine, Isocaine) Bupivacaine (Marcaine) Levobupivacaine(Chirocaine)Ropivacaine (Naropin) Articaine

42

16

16 NF

MediumMedium

Long

LongMedium

Xyloacaine hydrochloride spray

Indication

Spray Surface anesth in dental practice eg before inj, dental impressions, X-ray photograph, removal of calculus; in otorhinolaryngology eg puncture of the maxillary sinus & procedures in the nasal cavity, pharynx & epipharynx.

Dosage

Jelly Mucous membrane anesth Male 1st instillation: 7-10 mL. After penile clamp: 10 mL. Female A few mL.

Viscous liqd dumping syndrome 10 mL before meals, max tid.

Introduction of probes & catheters 15 mL. Esophagoscopy, esophagitis, pharyngitis 10 mL to be swished around in the mouth for at least 1 min before swallowing.

Spray Dental practice 1-5 application onto the mucous membranes for 1-2 min. Puncture of the maxillary sinus 3 applications. During delivery Up to 20 applications. Adult 70 kg Max: 200 mg (20 sprays).

Special precaution Avoid contact w/ eyes

Adverse Drug Reaction

Spray Stimulation & depression of cerebral cortex & medulla.

Thai FDA category

E-D (External Use-Dangerous Drug)

Preg. Category US FDA

B

BACKGROUND Postoperative

sore throat (POST)

• Postoperative sore throat (POST) after general anesthasia with ET intubaion has 40-100% of incidence

• Although the symptoms resolve spontaneously without treatment, prophylactic management for decrease frequency and severity is still recommend for quality of postoperative careSeveral

pharmacological method

• suggested including Benzydamine HCl, is a NSAIDs that also has analgesic, anti pyretic, antimicrobial properties. It has been reported moderated to severe sore throat may be resolved with gargling Benzydamine HCl

• patient may sustain numbness or sensation of tingling, dry mouth, thirst, and nausea because of Benzydamine HCl by gargling or oropharyngeal sprayCombes et al.

• demonstrated that mucosal damage occurring at the cuff level causative factor for tracheal morbidity

Hypothesis

The hypothesis of this study was

That simply spraying

Benzydamine hydrochloride

on the endotracheal cuff will provide

better prevention of postoperative

sore throat after extubation than

10% lidocaine, 2% lidocaine, or

normal saline spayed over the cuff

of the Endotracheal tube

Spraying on ETT cuff

Spraying on ETT cuff10%

lidocaine

2% lidoca

ine

Normal

saline

Benzydamin

e Hydrochlori

de

METHODS420 patients after inform consent,

with ASA status class I to III, aged 18 –

84 years

included to this prospective, randomized, and double-blind

study

scheduled for surgical under general anesthesia with

endotracheal intubation in supine position

METHOD

SExclus

ion criteri

as

Patient

undergoing• Oral cavity surger

y• Cervi

cal spine surger

y•Thyro

id surger

y

Patient with difficul

t airway (after more

than 1 orotracheal intuba

tion attempt )

Requiring

nasogastric tube

History of

perioperativ

e sore

throat

METHODS

The Benzydamine (comfflam®,

united biochemical,

asia)

• containing ethanol, glycerine, and mental as additive

• 10 puffs of Benzydamine HCl were sprayed on the ETT cuffs, which contain approximately 1.5 mg Benzydamine HCl

The 10%lidocaine(xylocaine spray

10%, AstraZeneca,

sweden)

• containing ethanol, polyethylene glycol 400, menthol, saccharin, an essence of banana as additive10 puffs of 10%lidocaine hydrochloride was sprayed on ETT cuff, which contain approximately 100 mg lidocaine hydrochloride

The 2%lidocaine (Xylocaine 2%, AstraZeneca)

• containing sodium chloride as an additive

• 10 puffs of 2%lidocaine hydrochloride were sprayed on the ETT cuffs, which contain approximately 20 mg lidocaine hydrochloride

The normal saline

• 10 puffs of normal saline sprayed on the ETT cuffs, which contain approximately 1ml normal saline

Patient were randomly into 4 groups by choosing blinded

envelopes.All study and normal saline were

contained in similarly figure bottles

METHOD

S

Sterile ETTs ( ILM endotracheal tube, Euromedi

csl, kedah,

Malaysia) with high volume,

low pressure

cuff

Male and female patient

received 7.5- and 7.0-mm internal

diameter ETTs,

respectively

Before intubation oxygen

was administe

red, adequate IV access

was establish

ed

standard american society of anesthesiologists clinical

monitoring was

applied

Sterile ETTs

performed

5 mins before

the induction

of anesthesi

a

METHODS

Induction with propofol 2 – 2.5 mg/k

g

With fentanyl 2-

3 µg/kg for

narcotic

With recoruniu

m 0.6 mg/kg for muscl

e relaxant

Intubation

by resident with at

least 2

years experience

attending by

physician who were blinded to group allocation

ETT cuff were inflat

ed with room air to achieve a seal at 20 cmH2

O

METHODS

Target-controlled infusion system with propofol

Intermittent fentanyl

Intermittent cisatracuriun/rocuronium

AnesthesiaN2O was not

used

METHOD

S At the end of surgery

METHODS

At 1, 6, 12, and 24, after extubation the patient were arked about sore throat and horseness

A single investigator who was blinded to the group allocation

1, no sore throat

2, mild sore throat (complains of sore throat only on arking )

3, moderated sore throat ( complains of sore throat on his or her own)

4, severe sore throat ( change of voice or horseness, association with throatpain)

Postoperative sore throat was graded by a modified 4 point scale

METHODS

A minimum of 91

patient was require in

each

group

To detect a

decrease incidence of

POST

from 40% to 20%

with a

power of 80%

and a

significant

level of 95%

Statistical

Analysis

was performed

using

the SPSS

for window version 15

Result are expressed as

Mean(SD),

Median with range, or percentage.

Patient age,

height, weight, duration

of surgery

were compared among

group and

tested statistica

lly by analysis

of variance

METHOD

SIncidence of POST and side effects among group

were tested by χ2 test

To avoid a type I error for

significant variable in χ2 testRecalculated all possible six 2x2

χ2 test by applying the

Bonerroni inequality

METHODS

•Severity of symptom among group were evaluated by Kruskal – wallis test

Differences in the severity of symptom

Both difference in the severity of symptoms and AUC were

tested by Kruskal – wallis analysis of variance and

followed by Dunn procedure values of p < 0.05 were considered statistically

significant

RESULT

There were patient withdrawn form • B

enzydamine 11 patient

• 10 % lidocaine 12 patient

• 2 % lidocaine 13 patient

• Normal saline 12 patient

Because of :• >

1 attemp at orotracheal intubation

• or nasogastric tube insertion during the operation

There were 372 patient enrolled in this study

RESULT

• In 24 hour evaluation period ; The highest incidences of POST occurred at sixth hour time interval after extubation

RESULT

RESULT

Significantly lower incidence of POST

in Benzyda

mine group than 10%

lidocaine, 2 %

lidocaine , and

normal saline (P < 0.05) at each

observation time point

Significantly

decreased severity of

POST

Compared with 2%

lidocaine and normal saline , the

10% lidocaine group had significant increased severity of

POST at 1,6,12 hour

after extubation

RESULT No significantly different among for the potential side effect to tracheal

intubation or study drugs

DISCUSSIONThis study demonstrated that

spraying Benzydamine hydrochloride

may reduce the incidence and severity of POST Compared with 10% lidocaine , 2% lidocaine ,and normal

saline

Unexpected finding; 10% lidocaine increased the severity

of POST

DISCUSSIONPOST• is one

of the common side effects associated with ETT

Cause• after

intubation or overinflated ETT

Complication• can

occur after even “a smooth” intubation

Immediate

POST may be primarily due to the action

of extubat

ionLate POST

related to

tracheal

mucosal

trauma

DISCUSSIONIn this study, the

highest incidence of POST occurred at the 6th hour after extubation

But not the 1th hour,

might be marked by

residual analgesic

effects after

general anesthesia

DISCUSSION

Indication of

Benzydamine

hydrochloride is

for relief painf

ul conditions

of mouth and throat such as

Tonsillitis

Sore throa

tRadiation

mucositis

Postorosurgical procedure

Periodonta

l procedure

PREVIOUS STUDIESdemons

trated topical

application of

Benzydamine

hydrochloride

to pharynx before LMA or

ETT insertio

n

decreased the

incidence of

POST

SIDE EFFECT OF THE TOPICAL BENZYDAMINE

HYDROCHLORIDESIDE EFFECT OF THE

TOPICAL BENZYDAMINE HYDROCHLORIDE

Local numbness

Burning

Stinging

sensation

Neasea or vomitting

Cough ,Dr

y mout

h,Throa

t discomfort

Drowsiness and headachewith may be evident

before induction of anesthesia

SIDE EFFECT OF THE TOPICAL BENZYDAMINE

HYDROCHLORIDETo avoid these side effects ; Applied

Benzydamide hydrochloride on the ETT cuff instead of

perioperative topical application at

oropharyngeal cavity

Found that ,this maneuver provided excellent prevention of POST and reduced

its incidence from placebo or 2%

lidocaine spray by >50 %

DISCUSSION

Therefore, applied on ETT cuff may provide* A simple and effective method * To attenuate the incidence and severity of POST after extubation

DISCUSSIONIn this study, found that

spraying 10% lidocaine on the ETT cuff

also increased the severity of

POST compared with 2% lidocaine or placebo

The addictive of 10%

lidocaine solution can

irritate tracheal mucosa

DISCUSSION

• menthol• ethanol

DISCUSSIONSaltani and Aghadavoudi, • Departme

nt of Anesthesiology, Isfahan Medical School, Isfahan University of Medical Sciences, and Health Services, Isfahan, Iran

To evaluate• the

efficacy of various ways of lidocaine application in reducing postoperative cough and sore throat.

Result• using intracuff lidocaine can avoid chemical irretation from the additives

DISCUSSIONIn this

study, the incidence of POST

no different between

2% lidocain

and normal saline group

Duration of

analgesic effect of lidocaine

spray applied to

oral mucosa is

< 15 minutes

At the end of

surgery (averagin

g 180 mins) the analgesic

effect already

dissappeared

LIMITATION1.No record of coughing or

bucking at the time of extubation

2.benzidamine hydrochloride is available under different trade

names in different countries

3.The addictives to 2% and 10%

lidocaine solution are different, which may influenced the

result

CONCLUSIONIn

conclusion,

PICO

Patients

Postoperative sore throat (POST) after general anesthasia with ET intubaion has 40-100% of incidence Although the symptoms resolve spontaneously without treatment, prophylactic management for decrease frequency and severity is still recommend for quality of postoperative care

Intervention

Spraying Benzydamine hydrochloride on the endotracheal cuff will provide better prevention of Postoperative sore throat after extubation than 10% lidocaine, 2% lidocaine, or normal saline spayed over the cuff of the Endotracheal tubeให. anesthesia maintanent เหมู�อนก�น postoperative pain control เหมู�อนก�น

Comparator

Incidence and severity of postoperative sore throat between Benzydamine Hydrochloride, 10% lidocaine, 2% lidocaine sprayed on Endotracheal tube cuff โดยื่ให. 0.9%NaCl เป0นกล1!มูควบค1มู

Outcomes

Applicationof Benzydamine hydrochloride on the ETT cuff effectively attenuates the incidence and severity of POST