17 January 2014

No. 02
BLUNTING THE INTUBATION
RESPONSE: FACT OR FICTION
Pur!"a#$
Moderator: C Evans
%&#!&'(&n$ o) Ana$#*"$*&!#
CONTENTS
+ECHANIS+ OF THE INTUBATION RESPONSE................................................4
BLUNTING THE HAE+O%,NA+IC RESPONSE..................................................7
OPIOI%S.................................................................................................................-
. 2 AGONISTS.....................................................................................................10
/ BLOCERS.......................................................................................................11
+AGNESIU+ SULPHATE 0+GSO41...................................................................12
NO2EL I%EAS......................................................................................................13
SU++AR, OF E2I%ENCE..................................................................................14
BENEFITS OF ATTENUATING THE RESPONSE...............................................17
CONCLUSION......................................................................................................20
REFERENCES......................................................................................................21
Page 2 of 27
OBJECTI2ES
Discuss the mechanism of the intubation response
Explore the various pharmacological methods to attenuate the intubation the
response
Attempt to determine the benefits of blunting the intubation response
Page 3 of 27
BLUNTING THE INTUBATION RESPONSE: FACT OR FICTION
INTRO%UCTION
ar!ngoscop! and tracheal intubation are noxious stimuli associated "ith a
transient increase in autonomic response# $ing et al described this response more
than %& !ears ago#
'()
*t is most often associated "ith an increase in heart rate and blood pressure and
is thought to be of little conse+uence in the health! individual but could be
deleterious in the vulnerable patient#
'2)
,his response varies "ith depth of
anaesthesia- duration and difficulties during lar!ngoscop! and intubation- and
certain patient factors including histor! of diabetes
'3)
and cardiovascular disease
'.)
'/)

+ECHANIS+ OF THE INTUBATION RESPONSE
0asic anatom!:
F&5ur$ 1: the sensor! innervation of the air"a!s
'%)
,he phar!nx: sensor! innervation 1 2lossophar!ngeal nerve supplies the
posterior third of the tongue- the fauces and tonsillae- anterior epiglottis and all
parts of the phar!nx "ith visceral sensor! 3bers#Motor innervation4 the phar!nx
receives efferent suppl! from the vagus nerve through its phar!ngeal branch#
'%)
Page . of 27
,he lar!nx: sensor! innervation 1 the internal lar!ngeal nerve- branch of the
superior lar!ngeal nerve- provides sensor! suppl! from the posterior epiglottis to
the vocal cords# ,he recurrent lar!ngeal nerve supplies the lar!nx belo" the vocal
cords and the trachea#
Motor innervation: the recurrent lar!ngeal nerve supplies all intrinsic muscles of
the lar!nx except the cricoth!roid muscles#
'%)

F&5ur$ 2: innervation of the lar!nx
'7)
5impl! put- "ith regards to sensor! innervation- the orophar!nx- posterior third of
the tongue and anterior part of the epiglottis are supplied b! glossophar!ngeal#
,he posterior epiglottis and distal air"a! structures are supplied b! branches of
the vagus nerve#
+$!"an&#6 o) *"$ &n*u7a*&on r$#'on#$
,he precise mechanism of the intubation response '*6) is elusive but it has been
established that it has both a s!mpathetic and paras!mpathetic element# ,he
effect is transient occurring 3& seconds after intubation and lasting for less than
(& minutes thereafter#
'7)
,he s!mpathetic response is a pol!s!naptic path"a! "ith
the glossophar!ngeal and vagus nerve forming the afferent arc to the s!mpathetic
nervous s!stem via the brain stem and spinal cord# ,his ensures a diffuse
autonomic response at the efferent side including increased firing of the cardio4
accelerator fibres and release of adrenergic mediators including norepinephrine-
epinephrine and vasopressin#
Page / of 27
,he net effect of this autonomic surge is an increased 0lood pressure '0P)- heart
rate '86)- pulmonar! arter! "edge pressure and decreased e9ection fraction#
,he paras!mpathetic reflex is monos!naptic and more common in children but
can occur in some adults# ,he reflex is mediated b! increased vagal tone at the
5A node#
'2)
,he haemod!namic response to lar!ngeal and endo4 tracheal intubation 'E,*) is
transient and in most patients thought to be of little conse+uence# *n patients "ith
coronar! arter! disease 'CAD)- h!pertension- raised intra cranial or intra ocular
pressure it ma! be associated "ith m!ocardial ischaemia- infarction- arrh!thmias-
cardiac failure- pulmonar! oedema and cerebral haemorrhage#
'/)
,he process of intubation comprises of different phases and these affect the
haemod!namic response differentl!# :rotracheal intubation consists of 2 phases:
direct lar!ngoscop! and passing of endotracheal tube through the vocal cords and
trachea#
';)
<our studies loo=ed at this differential effect# 5ing
';)
- 5hin9i
'(&)
and 8assan
'(()
concur that tracheal intubation and cuff inflation produce a substantial
haemod!namic effect- significantl! greater than lar!ngoscop! alone# 5hribman
'(2)
ho"ever found that orotracheal intubation did not significantl! contribute to the
haemod!namic effect# ,hese studies give the impression that greatest increase in
86 occurs during E,* and greatest increase in 0P occurs during lar!ngoscop!#
>ith no active attempt at blunting this haemod!namic response- increases in 50P
of .(4/3 mm8g- 86 2&423 and MAP of up to (&&? above baseline have been
documented#
'()'(3)
Page % of 27
BLUNTING THE HAE+O%,NA+IC RESPONSE
,he possibilities to offset or blunt the intubation response are numerous# :ptions
include pharmacological- peripheral bloc=s and variations in techni+ues including
various blades and conduits for intubations#
,his boo=let "ill onl! focus on pharmacological techni+ues#
Pharmacological options:
ocal anaesthetics
:pioids
@
2
agonists
A
2
bloc=ers
Mg5:
.
2abapentin- pregabalin
LIGNOCAINE:
,he effectiveness of lignocaine to blunt the intubation response '*6) is
contentious# Bumerous studies dating from (;%& have loo=ed at different doses-
timing and routes of administering ignocaine# <rom the discussion above on the
nerve suppl! of the lar!nx and the effect that tracheal intubation has on the *6 it is
apparent "h! lar!ngeal tracheal routes "ill not entirel! blunt the response#
'(.)'(/)

8amill et al and aurito et al both loo=ed at the *C route of ignocaine to blunt the
response to E,*#
8amill
'(.)
used a dose of (#/mgD=g- ivi (minute prior to E,* and compared this to
.ml of a .? solution spra!ed lar!ngealtracheall!# ,he group that received topical
lignocaine sustained significant increase in 86 and 0P after E,* that lasted for
more than 2 minutes# ,he authors note that the *C route did not completel!
attenuate the response as there "as still significant increase in 0P and 86
although onl! sustained for ( minute or less# aurito et al
'(%)
compared *C
ignocaine '2mgD=g) ( minute pre E,* to nebuliEed lignocaine .mgD=g (/
minutes prior to E,*# >ithin each group all haemod!namic variables increased
significantl!# >ith mean arterial pressures of (.&mm8g recorded#
Miller et al
'(7)
also failed to demonstrate that ignocaine attenuates the
haemod!namic response to E,*# ,he! studied ignocaine (#/mg ivi given (-2
and 3 minutes prior to E,*# 5=lar et al
'(7)
found that aerosol application of
lignocaine (2&mg "as effective in attenuating the both the 0P and 86 response
in adults# ,his "as applied for / minutes duration and 7#/ min prior to induction#
Carious other studies support the use of ignocaine (-/mgD=g ivi given bet"een 24
. minutes to attenuate the response# ,am et al
'(;)
and 5plinter et al
'2&)
could onl!
demonstrate benefit "ith regards to the 0P response- ho"ever 8elfman
'2()
found a
dose of (-/ mgD=g- given 2 minutes prior to E,*- to blunt both the 0P and 86
response#
,he principal limitation "hen comparing studies is heterogeneit! of the studies#
Carious doses- timings- pre medications and induction agents are used#
Page 7 of 27
At best- intra venous ignocaine "ill occasionall! blunt the 0P response and
almost never the 86 response# *f administered it should be at a dose of (-/mgD=g-
3 minutes prior to intubation
#'2)
,opical routes are not effective in blunting the intubation response and fe" studies
have sho"n convincing benefit of the aerosol route#
'22)
OPIOI%S
,he addition of opioids deepens the level of anaesthesia and therefor decreases
the s!mpathetic outflo"#
Alfentanil: numerous studies sho" that a dose of 3&FgD=g given bet"een (#/ and
2 minutes prior to intubation provides complete attenuation of the haemod!namic
response#
'23)'2.)'2/)'2%)
o"er dosages- (/FgD=g- seem to attenuate the 0P response but not the 86
response#
'2%)
*n the elderl! (&FgD=g given 34. minutes pre induction has also been sho"n to
completel! blunt the haemod!namic response#
'27)
8igher dosages have been associated "ith brad!cardia and h!potension#
'23)
<e" studies distinguish bet"een h!pertensive and non4h!pertensive patients#
:nl! Miller
'2/)
et al used patients from A5A (43 stages but did not specif! the
reason for the staging#
A dose of Alfentanil (&FgD=g given over 3& seconds has been suggested to be
effective in blunting the cardiovascular effect in h!pertensive patients on long term
treatment# *n this stud! 3D2& patients developed h!potension re+uiring Ephedrine#
'27)
6emifentanil:
,he rapid onset and short duration of 6emifentanil ma=es it an attractive drug for
attenuating the *6#
,hompson et al
'2;)
initiall! found that a dose of (FgD=g follo"ed b! and infusion of
&#/FgD=gDmin attenuated the haemod!namic response in health! adults# ,his dose
"as associated "ith profound brad!cardia and h!potension in half the patients#
A subse+uent stud!
'3&)
indicated that &#/FgD=g follo"ed b! an infusion of
&#2/FgD=gDmin "as as effective in blunting the response "ith no incidence of
brad!cardia or h!potension re+uiring treatment# ,he! also indicate that at the
higher doses- pre4treatment "ith gl!cop!rrolate 2&&Fg- decreases the incidence of
side effects#
Page 7 of 27
Maguire et al
'27)
demonstrated that a bolus dose of &#/FgD=g follo"ed b! infusion
at &#(FgD=gDmin effectivel! reduces the response to E,* in h!pertensive patients
on treatment# :f note is that all patients "ere pre4treated "ith gl!cop!rrolate 2&&
Fg# Bone of the patients developed a brad!cardia but 7D2& patients re+uired
rescue medication for h!potension# '50P 7&4(&& mm82)#
Most studies agree that a dose of 2FgD=g significantl! reduces the 0P and 86 and
that this dose is not recommended for the elderl! or compromised patient#
'22)
8art et al
'3()
compared 6emifentanil ' &#/FgD=g follo"ed b! an infusion of
&#(FgD=gDmin) and Alfentanil ' (&FgD=g) in elderl! patients# ,he stud! included
patients of A5A *4*** but excluded patients "ith evidence of cardiovascular
disease#
,he! concluded that both drugs similarl! attenuated the haemod!namic response
but that the incidence of h!potension in both groups 9ustifies caution in the elderl!#
<entan!l:
Bumerous studies have loo=ed at various doses and timing to administer <entan!l
and its effect on the intubation response# Gnsurprisingl!- high doses of /&47/FgD=g
completel! blunt the response but are associated "ith significant side effects#
'2)
*n normotensive A5A *D** patients various authors indicate that a dose of 2FgD=g
given bet"een 3-/4/ min pre E,* suppress the response#
'32)'33)
$autto et al
'3.)
and <eng at al
'33)
indicated that although the 0P response "as
attenuated at this dose- the 86 response "as not sufficientl! obtunded#
:thers indicate that a dose of /47FgD=g given bet"een 3-/4/ min pre E,*
completel! blunts the response#
'3.)'3/)'3%)
*n elderl! patients a dose of 3FD=g has been indicated to prevent a haemod!namic
response
#'37)

Again- most studies are heterogenic and difficult to compare# Dosages that seem
to be most effective are bet"een /4%FgD=g given 34/ minutes prior to E,*# Dose
reduction is prudent in the elderl!# >ith these doses there is a ris= for
complications including respirator! depression and dela!ed a"a=ening in short
cases#
'2)

5ufentanil:
,he use of 5ufentanil has been researched extensivel! in the paediatric
population but research in the adult population appears scant!#
$a! et al reported a dose of &-/4(FgD=g given 2 minutes pre E,* sufficientl!
bloc=ed the response in adults
#'37)
Hhang et al
'3;)
reported that in patients for heart valve replacement- a dose of
(FgD=g sufficientl! bloc=ed the 0P and 86 response# A dose of (#/FgD=g "as
associated "ith significant brad!cardia re+uiring Atropine administration in 27? of
cases#
Page ; of 27
*n t"o comparable studies in normotensive A5A *4*** patients- a bolus dose of
&#(FgD=g follo"ed b! an infusion of &#&(FgD=gDmin for / minutes prior to E,* "as
effective in blunting both the 0P and 86 response#
'.&)'.()
*n children- a dose bet"een &#24&#3FgD=g administered 2 min prior to E,* has
been found to significantl! attenuate the haemod!namic response to intubation#
'.2)
'.3)
Bone of the children in the higher range group experienced significant side
effects re+uiring treatment#
. 2 AGONISTS
5timulation of the pres!naptic @ receptors leads to reduced secretion of nor4
adrenaline and renin# Cagotonic effects that decrease the 86 are also present#
Most of the studies compare Clonidine as a premedication to various methods of
anaesthesia that included variable doses of <entan!l and Alfentanil#
5tudies indicate that- used in addition to a standard general anaesthetic- Clonidine
.4/FgD=g po given bet"een %&4;& minutes prior to surger! can be beneficial#
0enefits include reduced doses of opioids and induction agents- decreased
haemod!namic response to E,* and improved intraoperative haemod!namics#
,he ris= of brad!cardia is al"a!s present and "as treated "ith Atropine in some
of the studies#
'..)'./)'.%)'.7)'.7)
Dra"bac=s of Clonidine include long duration of onset- prolonged duration of
action and therefore the ris= of post4operative sedation in short procedures as "ell
as the ris= of h!potension and brad!cardia#
'2)'..)
Dexmedetomidine is a highl! selective @
2
agonist# A biphasic cardiovascular
response has been described# After a bolus of (FgD=g- a transient increase in 0P
and decrease in 86 is seen# ,his is thought to be due to stimulation of @
2
receptors in vascular smooth muscle# ,he vasoconstriction effect thus appears
before the central effects# ,his response can be decreased but not completel!
avoided b! giving the bolus dose as an infusion over (& minutes#
'.;)
Aho et al
'/&)
sho"ed in health! patients a bolus infusion of &#(2FgD=g over (& min
follo"ed b! an infusion of &#&&%FgD=g significantl! reduced the 86 but not the 0P
response to E,*# :f note is that .&? of the patients in the Dexmedetomidine
group re+uired Atropine to treat brad!cardia#
Iaa=ola et al
'/()
found an infusion of &#%FgD=gDmin (& minutes prior to E,*
reduced the 0P and 86 response in patients presenting for ophthalmic surger!#
0a9"a et al
'/2)
indicated that an infusion of (FgD=g over 2& minutes attenuated but
did not completel! obtund the response to E,*# Bone of the patients in this stud!
had a significant brad!cardiac or h!potensive episode ho"ever onl! health! A5A *
patients "ere included#
Page (& of 27
Menda et al investigated patients undergoing fast trac= CA02 surger!# An
infusion of (FgD=g "as given over (/ minutes# ,his "as compared to a placebo
group# ,heir conclusion "as that Dexmedetomidine can safel! be used to
attenuate the haemod!namic response# ,he incidence of h!pertension post
intubation in the placebo group "as statisticall! significant# ,he incidence of
h!potension "as not statisticall! significantl! bet"een the 2 groups#
'/3)
5ulaiman et al
'/.)
confirm these results but at much lo"er doses# %& patients for off
pump CA02 "ere randoml! allocated to a Dexmedetomidine group or placebo
group# An infusion of &#/FgD=g over (& minutes found better haemod!namic
control post E,* in the Dexmedetomidine group# Bo adverse effects needing
treatment "ere observed# 5ignificantl!- almost /&? of the patients in each group
"ere on A4bloc=ers pre4operativel!#
*n summar!- from the above studies- it appears that doses bet"een &#/4(FgD=g as
an infusion over (&42& minutes prior to E,*- in addition to lo" dose opioids-
decrease the response to E,* and improve haemod!namics#
,he ris= of h!potension and brad!cardia should al"a!s be considered# A recent
meta4anal!sis confirmed- in cardiac patients for non4cardiac surger!- peri4
operative Dexmedetomidine significantl! increased the incidence of h!potension
and brad!cardia#
'//)
/ BLOCERS
abetolol has a combination of @ and A bloc=ade# ,he @ bloc=ade is specific for @
(
and non4specific for A bloc=ade# ,he ratio of @
(
to A bloc=ing effect is (:7# *t has an
onset of (4/ minutes and a half4life of up to /#/ hours#
'72)
*nanda et al
'%()
compared abetolol '/mg and (&mg) to ignocaine '(&&mg) and a
placebo group in health! patients presenting for general surger!#
abetolol (&mg ivi 'JD4 &#(.mgD=g) 2 minutes prior to E,* bloc=ed the 86
response better than the other 2 groups but the 0P response "as the same in all
four groups#
Chung et al
'%2)
confirmed these findings "ith a larger dose of &#.mgD=g
administered / minutes prior to E,*#
eslie et al
'%3)
compared doses bet"een &#2/mgD=g to (mgD=g# *t "as found that
abetalol effectivel! attenuated the 86 and 0P response in a dose dependant
manner# 0ut the! also state that although the higher doses bloc= the 0P
response- the! are at the expense of significant post intubation h!potension#
:ne of the main concerns of abetalol is the prolonged duration of action#
Esmolol is a cardio selective A bloc=er "ith rapid onset and offset#
'72)
*t reaches
pea= blood levels in about 2 minutes and has an approximated half4life of ;
minutes#
'2)
Page (( of 27
5everal studies have assessed the effectiveness of Esmolol in blunting the
response to E,*# As "ith man! of the other drugs mentioned- little consensus
has been reached "ith regards to optimal dose- time and ris= of side effects in the
different population groups#
A recent meta4anal!sis
'/)
attempts to determine the optimal dose of Esmolol
needed to minimiEe the response to E,* and decrease post intubation
h!potension# ,he anal!sis includes 37 studies and concludes that a loading dose
of /&&FgD=g over . minutes follo"ed b! an infusion of 2&&43&&FgD=gDmin is the
best approach# *t also states that a dose dependant ris= of h!potension is entailed
during induction and its routine use is not recommended#
A comment on this meta4anal!sis is that of the 37 studies evaluated- onl! %
studies evaluated the use of Esmolol in patients "ith h!pertension or coronar!
arter! disease# A sub anal!sis could not be done as the numbers "ere insufficient#
Bevertheless these % studies indicated that neither the effectiveness of the drug
nor the magnitude of adverse effects "ere seemingl! different from the studies in
health! patients#
:f note is that (; of the included studies included the use of different opioids as
premedication or as part of induction#
+AGNESIU+ SULPHATE 0+GSO
4
1
Mg5:. is involved in several ph!siological processes including control of
vasomotor tone- cardiac excitabilit! and release of neurotransmitters# ,hrough
various methods it causes vasodilation and decreases release of catecholamines
from the nerve terminals and adrenal gland#
'/%)
A small but elo+uent stud! b! Iames et al
'/7)
studied the effect of %&mgD=g Mg5:
.
pre4treatment on the cardiovascular response to E,* and catecholamine release#
(% health! male patients "ere randoml! allocated to a placebo group or the
Mg5:
.
group# All patients "ere pre4medicated "ith DiaEepam (&mg po ( hour pre
surger!# Bo opioids "ere used during induction# Although Mg5:
.
caused a slight
increase in 86 after in9ection- the increase post intubation "as still less "hen
compared to the placebo group#
0P readings "ere significantl! lo"er in the Mg5:
.
group post E,*# ,he stud!
also indicated that Mg5:
.
can significantl! attenuate catecholamine output at the
time of E,*#
Puri et al
'/7)
studied the use of Mg5:
.
in patients "ith coronar! arter! disease
presenting for CA02# A dose of /&mgD=g'nK(;) "as compared to ignocaine
(mgL=g 'nK(7)#
Page (2 of 27
,he! concluded that Mg5:
.
attenuated the haemod!namic response to E,*
more effectivel! than ignocaine# Bone of the patients in the Mg5:
.
had
significant 5, changes- compared "ith three patients in the ignocaine group#
Panda et al
'/%)
determined that the minimal effective dose of Mg5:
.
needed to
attenuate the intubation response in controlled h!pertensive patients "as
3&mgD=g#
8igher dosages "ere associated "ith significant h!potension#
Iames et al
'/;)
compared ignocaine '(-/mgD=g)- Alfentanil '(&FgD=g) and Mg5:
.
'.&mgD=g) in h!pertensive- proteinuric pregnant patients# 5!stolic blood pressure
exceeded baseline values the first / min after tracheal intubation in the lignocaine
group- but no mean increase in pressure occurred in the t"o other groups#
Alfentanil caused the least change in heart rate- but resulted in significant fetal
depression#
*n a subse+uent stud!
'%&)
- Mg5:
.
.&mgD=g "as compared to Mg5:
.
3&mgD=g "ith
Alfentanil 7#/FgD=g# ,he conclusion "as that both methods controlled the
haemod!namic response satisfactoril! but that the combination "as superior in
controlling both the 0P and 86 response# ,here "as no difference in fetal
outcome bet"een the t"o groups#
NO2EL I%EAS
2abapentin inhibits membrane voltage gated calcium channels# *t is being used
more fre+uentl! as an ad9unct for treatment of acute post4operative pain in the
setting of chronic pain#
'%()'72)
<assoula=i et al
'%()
studied the impact of their standard analgesic regime of
2abapentin- on the haemod!namic changes during E,*# .% A5A *4** patients
scheduled for elective h!sterectom! "ere randoml! allocated to receive
2abapentin .&&mg or placebo % hourl!- starting at noon the da! prior to theatre
'total dose (%&&mg)# Bo other premedication "as given and a standard induction
"as done "ith Propofol and Cisatracuruim# Bo opioids "ere given prior to
intubation# ,he! found that this regime attenuated the 0P response but not the 86
response#
$umari et al
'%2)
studied the effect of a single dose of ;&&mg given 2 hours pre4
operativel!# ,he onl! statisticall! significant effect "as noted at the (& minute post
E,* interval# Although this stud! came to the conclusion that a single dose is
effective in reducing the response to E,*- it is +uestionable since most authors
agree that the response to E,* lasts a maximum of (& minutes "ith the pea=
effect in the first fe" minutes# Bo mention is made of an anxiol!tic or opioid given
pre induction "ith Propofol 2#/mgD=g#
*n a similar stud! 0afna et al
'%3)
found that a single dose of (g- (hour pre op had a
statisticall! significant effect in controlling the 0P and 86# :nce again this stud!
"as conducted in health! patients for elective surger!#
Page (3 of 27
,he significant difference is that the patients "ere pre4medicated "ith MidaEolam
and <entan!l and induced "ith ,hiopentone /mgD=g# ,he most convincing stud!
of a single dose of 2abapentin is Memis et al
'%.)
# ;& health! patients "ere
randomised to either a placebo- 2abapentin .&&mg or 7&&mg group administered
( hour before surger!# Bo other pre medications "ere given and no opioids "ere
used during induction# Patients "ere induced "ith Propofol 2mgD=g# ,he! sho"ed
a statisticall! significant decrease in 86 and 0P- in the 7&&mg group- at all
intervals recorded "hen compared to the other groups#
Pregabalin is structurall! but not functionall! related to gamma4aminobut!ric acid
'2A0A)# *t acts b! inhibiting the s!nthesis of the neurotransmitter glutamate#
'72)
*n
a prospective stud! 0ha"na et al
'%/)
randoml! allocated ;& health! patients to
either a placebo 'group *)- Pregabalin 7/mg 'group **) or Pregabalin (/&mg 'group
***) group administered ( hour pre induction# 5tatisticall! significant increases in
0P post E,* "ere seen in group * and ** "hile a significant decrease "as seen in
group ***# ,here "as no significant decrease in 86 in an! group# ,hese results
are confirmed b! another stud!# 5under et al
'73)
found that a single dose of
Pregabalin (/&mg attenuated the response to E,* in patients presenting for
cardiac surger!# *n contrast to 0ha"na et al this stud! sho"ed a statisticall!
significant reduction in 86 response to E,*# Possible reasons for this include that
the 5under trial "as done in cardiac patients and a therefor a significant
proportion of patients "ere on rate modulating medication# Another contributing
factor is that the 5under stud! used opioids a part of the induction#
Page (. of 27
SU++AR, OF E2I%ENCE
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Page (/ of 27
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Tr$a*$8 HT
&<& = = 2-
F$n*any( 2FgD=g
34/ min pre
E,*
ivi moderate moderate 32
2FgD=g ivi M none 33-3.
/47FgD=g ivi M M 3.43%
R$6&)$n*an&( &#/FgD=g
bolus then
&#2/FgD=gDmin
ivi M M 3&
&#/FgD=g then
&#(FD=gDmin in
8,D elderl!
ivi M M 27-3(
Su)$n*an&( (FgD=g 2min
prior to E,*
ivi M M 3743;
&#(FgD=g then
&#&(FgD=gDmin
for / min
ivi M M .&-.(
C(on&8&n$ /FgD=g
%&4;& pre
E,*
po moderate moderate ./4.7
%$>6$8$*o
6&8&n$
&#(2FgD=g
over (&min
then
&#&&%FgD=gD
min
ivi M /&
&#%FgD=gDmin
over (& min
ivi M M /(
(FgD=g over
2& min
ivi moderate moderate /2
&#/FgD=g over
(& minutes- in
cardiac pt
ivi moderate moderate /.
La7$*o(o( (&mg ivi M %(
&#.mgD=g ivi M %2
E#6o(o( /&&FgD=g
over .min
then 2&&4
3&&FgD=gDmin
ivi moderate M /
Pr$5a7a(&n 7/mg-( hour
pre E,*
po x %/
Page (% of 27
(/&mg-( hour
pre op
po M %/-73
Ga7a'$n*&n .&&mgD%
hourl!
po M %(
;&&mg-2hour
s pre E,*
po M %2
(g- ( hour pre
E,*
po M M %3
.&&mg ( hour
pre E,*
po M
7&&mg-( hour
pre op
po moderate moderate %.
+a5n$#&u6 %&mgD=g ivi M moderate /7
3&mgD=g ivi M moderate /%
.&mgL=g ivi M moderate /;4%&
/&mgL=g ivi M moderate /7
MK effect on parameter
BENEFITS OF ATTENUATING THE RESPONSE
Central to the +uestion regarding the benefit of blunting the *6 is the differentiation
bet"een final outcomes 'death- peri4operative M*) and process outcome
'ischemia-h!potension-tach!cardia-arrh!thmias)
#'2)
As seen- numerous studies have been done to modif! the response to E,*# ,he!
invariabl! report on variables such as 86- 0P- rate4 pressure ratio and 5,
changes#
Most studies record this for approximatel! (& minutes post E,*# Cer! fe" report
on the influence these have on final outcomes# '%%)
,herefore- benefits of the techni+ues described are presumptive and "e assume
that b! altering the haemod!namic response to E,*- "e "ill improve or alter
outcome#
0oth 86 and 0P are determinants of deliver! and demand of ox!gen# An increase
in heart rate deleteriousl! affects both suppl! and demand of ox!gen# 0P is
related to cardiac output 'C:) and s!stemic vascular resistance '5C6)# A change
in either C: or 5C6 "ill result in a compensator! change in the other#
8!pertension can therefore affect both suppl! and demand
'%%)
# All other organs but
most important to this discussion- the brain- heart and =idne!s depend on
s!stemic pressure to maintain perfusion pressure#
,herefore it is inferred that certain patients cannot tolerate the conse+uences of
the haemod!namic response to E,*#
Page (7 of 27
,hese "ould unarguabl! include eclamptic patients due to the ris= of cerebral
haemorrhage and pulmonar! oedema# :ther such populations "ould include
patients "ith raised intra cranial pressure- patients presenting for cardiac surger!
or patients "ith acute h!pertensive urgenciesDemergencies#
,he gre! area appears "hen researching the benefit in patients "ith ris= factors
for cardiovascular disease but "ith no target organ damage presenting for non4
cardiac surger!#
6eich et al
'%7)
performed a retrospective sub anal!sis 'nK7;7)# ,he aim "as to see
if intra4operative deviations of 86 and 0P "ere associated "ith peri4operative
mortalit! and morbidit!# All patients "ere undergoing complex non cardiac surger!
and controlled for the influence or pre4operative medical conditions#
Deviations "ere defined as 86N ./ DO((&- MAPN//DO(&&mm8g and
50PN7&DO(%&mm8g or an! duration of time#
,he primar! end4point "as negative surgical outcome 'B5:) including post4
operative hospital sta! O (&da!s "ith a morbid condition or death during the same
hospitaliEation#
,here "as no strong association bet"een B5: and variations in haemod!namics
in surgeries lasting less than 22& min#
<or surgeries lasting more than 22&min there "as a strong association "ith lo"
MAP and increased 86# *ncreased 86 "as the stronger predictor#
*ncreased 86 and increased 50P "ere both strong- independent predictors of
adverse outcomes in surgeries lasting more than 22& minutes#
0i9=er et al
'%7)
studied the association bet"een ( !ear mortalit! and intra operative
h!potension '*:8)# ,his retrospective revie" 'nK(7&/) included patients
undergoing general and vascular surger!# Among others- the stud! examines the
effect of h!potension- defined in .7 different "a!s- on mortalit!#
After ad9usting for confounding variables- the regression anal!sis failed to sho"
an! association bet"een *:8 and ( !ear mortalit!#
,he onl! positive associations "ere bet"een advanced age- histor! of
h!pertension- prolonged surger! and *:8# ,his stud! failed to indicate "hat
degree and "hat duration of *:8 can be tolerated during surger!#
Mon= et al
'%;)
studied the association bet"een anaesthetic management and one
!ear mortalit! after non cardiac surger!# ,his stud! included 77& patients#
Multivariate anal!sis indicated 3 significant predictors of ( !ear mortalit!# :ne of
these predictors included *:8# 5!stolic h!potension increased mortalit! ris= b!
(#&3%'66) per minute belo" N7&mm8g# ';/ ? C* (#&&%4(#&%%)
Page (7 of 27
>alsh et al
'7&)
anal!sed prospectivel! gathered data from over 33 &&& patients
undergoing non cardiac surger!# ,he! found that a MAP N//mm8g "as
independentl! associated "ith the development of acute =idne! in9ur!- m!ocardial
in9ur! and cardiac complications# ,his ris= escalates "ith time spent under
MAPN//mm8g but there does not appear to be an! safe amount of time to spend
under a MAPN//mm8g#
A Cochrane revie" from 2&(3
'7()
had the primar! ob9ective to determine the
effectiveness of pharmacological agents in preventing the morbidit! and mortalit!
resulting from the haemod!namic changes during E,*# 5econdar! ob9ectives
included the effect on arrh!thmias and on EC2 changes associated "ith
ischemia# ,he revie" included 72 randomised controls trials that studied the effect
of 32 different drugs belonging to different pharmacological classes#
:nl! 2 trials mentioned the primar! outcome of morbidit! and mortalit! and both
these trials reported no ma9or morbidit! or mortalit!# <rom this revie" there is no
observed evidence that pharmacological agents influence morbidit! or mortalit!#
,his revie" also suggests that the pre4treatment "ith pharmacological
interventions is associated "ith a decreased ris= of arrh!thmias# Bone of the
studies commented on the percentage of patients re+uiring treatment for the
observed arrh!thmias or an! further conse+uences related to the rh!thm
disturbances#
3( studies included m!ocardial ischaemia# Bone of the studies examined the final
outcome of intra operative evidence of ischaemia in the post4operative period#
:ver all- pharmacological intervention reduced the ris= of m!ocardial ischaemia#
0ut all the evidence came from ; trials and therefor it should be treated "ith
caution# <urther- ocal anaesthetic "as the onl! contributor in this sub group but
the anal!sis "as dominated b! a single stud!# A bloc=ers "ere the largest
contributor in this sub group anal!sis and sho"ed no advantage# :nce again this
should be treated "ith caution as the studies "ere mostl! underpo"ered to loo=
for this complication#
*n the sub group anal!sis comparing high ris= '(7 studies) to lo" ris= patients-
treatment "as effective in lo" ris= patients but not in high ris= patients# ,his could
be due to underpo"ering of the studies or due to other medications not accounted
for in the high ris= group# :verall all the studies "ere underpo"ered to detect a
reduction in the ris= of EC2 abnormalities#
*n summar!- in lo" ris= patients- pre4induction use of pharmacological agents
reduces the ris= of arrh!thmias from (3? to .? and appears effective in reducing
the ris= of m!ocardial ischaemia#
*n high ris= patients pharmacological agents resulted in a reduction in the ris= of
arrh!thmias but not in EC2 evidence of ischaemia#
,he above summar! must be vie"ed "ith the limitations discussed previousl!#
Page (; of 27
CONCLUSION
Evidence of the hemod!namic effect to E,* has been available for more than %&
!ears# ,he precise mechanism is still being debated but the immediate
ph!siological conse+uences are "ell documented#
Bumerous methods are available to attenuate this response and literarll!
thousands of trials have been done to this regard# ,he long4term conse+uences
and effect on morbidit! and mortalit! of the intubation response in different
surgical population groups are not "ell established# ,herefore the benefit of
attenuating this response in all patients is not clear cut#
,he interventions applied to blunt the response are not "ithout complications-
some of "hich have their o"n effect on morbidit! and mortalit!#
*n certain high ris= groups the benefit is inferred as it "ould be unethical to stud!
the conse+uence of not blunting the response#
Modification of the haemod!namic response to E,* is an admirable ob9ective and
clearl! "arranted in a select group of patients in "hom a transient h!per4d!namic
episode can lead to catastrophe# 8o"ever- extending the principle of vigilant
haemod!namic control to the entire peri4operative period holds more logic than
tunnel vision surrounding the 2 minutes around intubation#
Page 2& of 27
REFERENCES
(# $*B2 0D- 8A66*5 C-# 6eflex circulator! responses to direct lar!ngoscop!
and tracheal intubation performed during general anesthesia# Anesthesiolog!#
(;/( 5ep-(2'/)://%1%%#
2# $ovac # Controlling the hemod!namic response to lar!ngoscop! and
endotracheal intubation# I# Clin# Anesth# Anesth# (;;% <ebP7'():%317;#

3# Cohra A- $umar 5- Charlton AI-#Effect of diabetes mellitus on the
cardiovascular responses to induction of anaesthesia and tracheal intubation#
0r# I# Anaesth (;;3 Aug Q7('2):2/71%(#
.# o" IM- 8arve! I,- Pr!s46oberts C- 5tudies of anaesthesia in relation to
h!pertension# C**: Adrenergic responses to lar!ngoscop!# 0r# I# Anaesth#
Q*nternetR# (;7% Ma!P/7'/):.7(17#
/# <*2GE6ED: E and 2A6C*A4<GEB,E5 E# M# Assessment of the efficac! of
esmolol on the haemod!namic changes induced b! lar!ngoscop! and tracheal
intubation : A meta4anal!sis# Acta Anaesthesiol 5cand# 2&&(P('(():(&((122#
%# 5immons 5- 5chleich a# Air"a! regional anesthesia for a"a=e fiberoptic
intubation# 6eg# Anesth# 2&&2 MarP27'2):(7&1;2#
7# BS5:6A 4 ,he Be" Sor= 5chool of 6egional Anesthesia 4 6egional T ,opical
Anesthesia for Endotracheal *ntubation
http:DD"""#n!sora#comDtechni+uesDnerve4stimulator4and4surface4based4ra4
techni+uesDhead4and4nec=4bloc=aD3&224regional4topical4anesthesia4for4
endotracheal4intubation#html
7# 2upta A- >a=hloo 6- 2upta C- Mehta A- $apoor 00# Comparison of Esmolol
and ignocaine for Atttenuation of Cardiovascular 5tress response to
ar!ngoscop! and Endotracheal *ntubation# 2&&;P(('2):&13#
;# 5ingh 5# Cardiovascular changes after the three stages of nasotracheal
intubation# 0r# I# Anaesth 2&&3 Bov (-;('/):%%717(#
(&#5hin9i ,- MiEutani ,- Masa!u=i M# 8emod!namic responses to tracheal
intubation "ith lar!ngoscope versus light"and intubating device ',rachlight) in
adults "ith normal air"a!# Anesth# Analg# 2&&2 p# .7&1.7.#

((#8assan 82- el45har=a"! ,S- 6enc= 8- Mansour 2- <ouda A# 8emod!namic
and catecholamine responses to lar!ngoscop! "ith vs# "ithout endotracheal
intubation# Acta Anaesthesiol# 5cand# (;;( p# ..217#

(2#5hribman AI- 5mith 2- Achola $I# Cardiovascular and catecholamine
responses to lar!ngoscop! "ith and "ithout tracheal intubation# 0r# I# Anaesth#
(;77 p# 2;/1;#
(3# Per=ins H0- 2unning M- Crill! I- oc=e! D- :U0rien 0# ,he haemod!namic
response to pre4hospital 65* in in9ured patients# *n9ur!- Elsevier tdP 2&(3 Ma!
..'/):%(7123#
Page 2( of 27
(.# 8amill I<- 0edford 6<- >eaver DC- Colohan A6# idocaine before
endotracheal intubation: intravenous or lar!ngotrachealV Anesthesiolog! -
(;7(//'/):/7717(# Available from:
(/# aurito CE- 0aughman C- 0ec=er 2-Effects of aerosoliEed andDor
intravenous lidocaine on hemod!namic responses to lar!ngoscop! and
intubation in outpatients# Anesth# Analg# (;77 p# 37;1;2#
(%# aurito CE- 0aughman C- 0ec=er 2- Effects of aerosoliEed andDor
intravenous lidocaine on hemod!namic responses to lar!ngoscop! and
intubation in outpatients# Anesth# Analg(;77 Apr-%7'.):37;1;2#
(7# Miller CD- >arren 5I# *C lignocaine fails to attenuate the cardiovascular
response to lar!ngoscop! and tracheal intubation# 0r# I# Anaesth# (;;& Aug
%/'2):2(%1;#
(7# 5=lar 0H- urie 5- EEri ,- idocaine inhalation attenuates the circulator!
response to lar!ngoscop! and endotracheal intubation# I# Clin# Anesth#
.'/):3721/#
(;# ,am 5- Chung <- Campbell M# *ntravenous lidocaine: optimal time of in9ection
before tracheal intubation# Anesth# Analg- (;77 :ctP%%'(&):(&3%17#
2&# 5plinter >M- Cerven=o <# 8aemod!namic responses to lar!ngoscop! and
tracheal intubation in geriatric patients: effects of fentan!l- lidocaine and
thiopentone# Can# I# Anaesth# (;7; IulP3%'.):37&1%#
2(# 8elfman 5M- 2old M*- Deisser EA- 8errington CA# >hich drug prevents
tach!cardia and h!pertension associated "ith tracheal intubation: lidocaine-
fentan!l- or esmololV Anesth# Analg# (;;( Apr -72'.):.721%#
22# >oods a >- Allam 5# ,racheal intubation "ithout the use of neuromuscular
bloc=ing agents# 0r# I# Anaesth# 2&&/ <ebP;.'2):(/&17#

23# Cra"ford DC- <ell D- Achola $I-Effects of alfentanil on the pressor and
catecholamine responses to tracheal intubation# 0r# I# Anaesth# (;77 p# 7&71
(2#

2.# Martineau 6I- ,ousignant CP- Miller D6- Alfentanil controls the
haemod!namic response during rapid4se+uence induction of anaesthesia#
Can# I# Anaesth# (;;& p# 7//1%(#
2/# Miller D6- Martineau 6I- :U0rien 8- 8ull $A-#Effects of alfentanil on the
hemod!namic and catecholamine response to tracheal intubation# Anesth#
Analg# (;;3 p# (&.&1%#
2%# $orpinen 6- 5aarnivaara - 5iren $- 5arna 5# Modification of the
haemod!namic responses to induction of anaesthesia and tracheal intubation
"ith alfentanil- esmolol and their combination# Can# I# Anaesth# (;;/
AprP.2'.):2;713&.#
Page 22 of 27
27# $irb! *I- Borth"ood D- Dodson ME# Modification b! alfentanil of the
haemod!namic response to tracheal intubation in elderl! patients# A dose4
response stud!# 0r# I# Anaesth# (;77 p# 37.17#
27# Maguire a M- $umar B- Par=er I- 6o"botham DI- ,hompson IP#
Comparison of effects of remifentanil and alfentanil on cardiovascular
response to tracheal intubation in h!pertensive patients# 0r# I# Anaesth# 2&&(
IanP7%'():;&13#
2;# ,hompson IP- 8all AP- 6ussell I- Effect of remifentanil on the haemod!namic
response to orotracheal intubation# 0r# I# Anaesth# (;;7 p# .%71;#
3&# 8all AP- ,hompson IP- eslie B a Comparison of different doses of
remifentanil on the cardiovascular response to lar!ngoscop! and tracheal
intubation# 0r# I# Anaesth# 2&&& IanP7.'():(&&12#

3(# 8abib A5- Par=er I- Maguire AM- 6o"botham DI- 58:6,
C:MMGB*CA,*:B Effects of remifentanil and alfentanil on the cardiovascular
responses to induction of anaesthesia and tracheal intubation in the elderl!#
0r# I# Anaesth# 2&&2P77'3):.3&13#

32# Channaiah C0- Char! $- Cl= I- o"4dose fentan!l : hemod!namic response
to endotracheal intubation in normotensive patients# Arch Med 5ci#
2&&7P3'september):2;31;#
33# 5ong 8# 5mall4Dose <entan!l: :ptimal ,ime of *n9ection for 0lunting the
Circulator! 6esponses to ,racheal *ntubation# Anesth# Analg# (;;7P7%:%/71%(#

3.# $autto GM# Attenuation of the circulator! response to lar!ngoscop! and
intubation b! fentan!l# Acta Anaesthesiol# 5cand# (;72 IunP2%'3):2(712(#

3/# <eng C$- Chan $8- iu $B- :r C8- ee ,S# A comparison of lidocaine-
fentan!l- and esmolol for attenuation of cardiovascular response to
lar!ngoscop! and tracheal intubation# Acta Anaesthesiol##(;;% Iun 3.'2):%(17#
3%# Martin DE- 6osenberg 8- Au=burg 5I-o"4dose fentan!l blunts circulator!
responses to tracheal intubation# Anesth# Analg (;72 Aug%('7):%7&1.#
37# Chung <- Evans D# o"4dose fentan!l : haemod!namic re4 sponse during
induc4 tion and intubation in geriatric patients# Can# I# Anaesth#
(;7/P32'%):%2217#

37# $a! 0- Bolan D- Ma!all 6- 8eal! ,E# ,he effect of sufentanil on the
cardiovascular responses to tracheal intubation# Anaesthesia (;77 Apr
2&(3P.2'.):3721%#
3;# Hhang 8- 2uo W# QEffect of different doses of sufentanil on stress responses to
tracheal intubation in patients undergoing heart valve replacement surger!R#
Hhong Ban Da Mue Mue 0ao# Si Mue 0an 2&&7 Iun

Page 23 of 27
.&# *ABBGHH* E- *ABBGHH* M- C*6*: C- C*:A 2- PA6*5* 6- CE6G* A- et
al# Peri4intubation cardiovascular response during lo" dose remifentanil or
sufentanil administration in association "ith propofol ,C*: A double blind
comparison# Minerva Anestesiol# Minerva medicaP 2&&. 7&'3):(&;1(/#

.(# Casati A- <anelli 2# sfenta adult#pdf# Eur# I# Anaesthesiol# 2&&(P(7:(&71(2#

.2# Mue <5- Mu SC- iu S- Sang WS- iao M- iu 8P- et al# Different small4dose
sufentanil blunting cardiovascular responses to lar!ngoscop! and intubation in
children: a randomiEed- double4blind comparison# 0r# I# Anaesth# 2&&7 Ma!
(&&'/):7(7123#
.3# Mue <5- iu $P- iu S- Mu SC- Assessment of small4dose fentan!l and
sufentanil blunting the cardiovascular responses to lar!ngoscop! and
intubation in children# Paediatr# Anaesth# Q*nternetR# 2&&7 Iun Qcited 2&(3 Bov
2%RP(7'%):/%717.# Available from:

..# 2hignone M- Boe C- Calvillo :- Wuintin # Anesthesia for ophthalmic surger!
in the elderl!: the effects of clonidine on intraocular pressure- perioperative
hemod!namics- and anesthetic re+uirement# Anesthesiolog!# (;77 p# 7&71(%#

./# 2hignone M- Wuintin - Du=e PC- Effects of clonidine on narcotic re+uirements
and hemod!namic response during induction of fentan!l anesthesia and
endotracheal intubation# Anesthesiolog!# (;7% p# 3%1.2#

.%# Ma9umdar 5# Comparative evaluation of oral clonidine and midaEolam as
premedication on preoperative sedation and lar!ngoscopic stress response
attenuation for the patients undergoing general anaesthesia# *nt# I# Med# public
8eal# 2&(3P3'3):2&&17#

.7# 2upta $- 5harma D- 2upta P$# :ral premedication "ith pregabalin or
clonidine for hemod!namic stabilit! during lar!ngoscop! and laparoscopic
cholec!stectom!: A comparative evaluation# 5audi I# Anaesth# Q*nternetR# 2&((
Apr Qcited 2&(3 Bov 2%RP/'2):(7;17.# Available from:
http:DD"""#pubmedcentral#nih#govDarticlerender#fcgiV
artidK3(3;3(2TtoolKpmcentreETrendert!peKabstract
.7# aisalmi M- $oivusalo a M- Calta P- ,i==anen *- indgren # Clonidine provides
opioid4sparing effect- stable hemod!namics- and renal integrit! during
laparoscopic cholec!stectom!# 5urg# Endosc# 2&&( Bov (/'(():(33(1/#
.;# 0loor 0C- >ard D5- 0elleville IP- MaEe M# Effects of intravenous
dexmedetomidine in humans# **# 8emod!namic changes# Anesthesiolog! (;;2
Dec77'%):((3.1.2#
/&# Aho M- Er=ola :- $allio A- 5cheinin 8- $orttila $# Dexmedetomidine infusion
for maintenance of anesthesia in patients undergoing abdominal h!sterectom!#
Anesth# Analg# (;;2 DecP7/'%):;.&1%#
Page 2. of 27
/(# Iaa=ola M- Ali4Mel==ilX ,- $anto I-# Dexmedetomidine reduces intraocular
pressure- intubation responses and anaesthetic re+uirements in patients
undergoing ophthalmic surger!# 0r# I# Anaesth#(;;2 Iun %7'%):/7&1/#
/2# 0a9"a 5I5- $aur I- 5ingh A- Parmar 5- Attenuation of pressor response and
dose sparing of opioids and anaesthetics "ith pre4operative dexmedetomidine#
*ndian I# Anaesth 2&(2 Mar /%'2):(2317#

/3# Menda <- $Yner :- 5a!in M- ,Zre 8# Dexmedetomidine as an ad9unct to
anesthetic induction to attenuate hemod!namic response to endotracheal
intubation in patients undergoing fast4trac= CA02# Ann# Card# anaesthesias
Card# Anaest-2&(&-(3'():(%12(#
/.# 5ulaiman 5- $arthe=e!an 60- Ca=amudi M- ,he effects of dexmedetomidine
on attenuation of stress response to endotracheal intubation in patients
undergoing elective off4pump coronar! arter! b!pass grafting# Ann# Card#
Anaesth- 2&(2 -(/'():3;1.3#
//#0iccard 0M- 2oga 5- de 0eurs I# Dexmedetomidine and cardiac protection for
non4cardiac surger!: a meta4anal!sis of randomised controlled trials#
Anaesthesia-2&&7 IanRP%3'():.1(.#
/%# Panda B0- 0harti B- Prasad 5# Minimal effective dose of magnesium sulfate
for attenuation of intubation response in h!pertensive patients# I# Clin# Anesth#
Q*nternetR# ElsevierP 2&(3 MarP2/'2):;217#
/7# Iames M<- 0eer 6E- Esser ID# *ntravenous magnesium sulfate inhibits
catecholamine release associated "ith tracheal intubation# Anesth# Analg#
(;7; IunP%7'%):7721%#

/7# Puri 2D- Marudhachalam $5- Chari P- 5uri 6$# ,he Effect of Magnesium
5ulphate on 8emod!namics and *ts Efficac! in Attenuating the 6esponse to
Endotracheal *ntubation in Patients "ith Coronar! Arter! Disease# Anesth#
Analg# (;;7P77'.):7&71((#

/;# Allen 6>- Iames M<- G!s PC# Attenuation of the pressor response to tracheal
intubation in h!pertensive proteinuric pregnant patients b! lignocaine-
alfentanil and magnesium sulphate# 0r# I# Anaesth- (;;( <eb-%%'2):2(%123#
%&# Ashton >0- Iames M<- Ianic=i P- G!s PC# Attenuation of the pressor
response to tracheal intubation b! magnesium sulphate "ith and "ithout
alfentanil in h!pertensive proteinuric patients undergoing caesarean section#
0r# I# Anaesth (;;( Dec %7'%):7.(17#
%(# <assoula=i a- Melemeni a- Paras=eva a- Petropoulos 2# 2abapentin
attenuates the pressor response to direct lar!ngoscop! and tracheal
intubation# 0r# I# Anaesth- 2&&% Iun-;%'%):7%;173
Page 2/ of 27
%2# $umari *- Pathania C5# A Prospective 6andomised Double40lind Placebo
Controlled ,rial of :ral 2abapentin in Attenuation of 8aemod!namic
6esponses During ar!ngoscop! and ,racheal *ntubation# I# Anaesthesiol#
Clin# Pharmacol# 2&&;P2/'.):.3;1.3#
%3# 0afna G- 2o!al C$- 2arg A# A comparison of different doses of gabapentin to
attenuate the haemod!namic response to lar!ngoscop! and tracheal
intubation in normotensive patients# I# Anaesthesiol# Clin# Pharmacol# 2&((
Ian RP27'():.31%#
%.# Memis D- ,uran A- $aramanlioglu 0- ,iire M# :riginal Article 2abapetitin
reduces cardiovascular responses to lar!ngoscop! and tracheal intubation#
Eur# I# Anaesthesiol# 2&&%P23'7):%7%1;&#

%/# 6astogi 0- 2upta $- 2upta P$- Agar"al 5- Iain M- Chauhan 8# :ral
pregabalin premedication for attenuation of haemod!namic pressor response
of air"a! instrumentation during general anaesthesia: A dose response stud!#
*ndian I# Anaesth- 2&(2 IanP/%'():.;1/.#

%%#,homson *# Editorial ,he haemod!namic response to intubation : a perspective
a rrponse h%mo4 d!nami+ue a l U intu4 bation : un perspective# Can# I#
Anaesth# (;7;P3%'.):3%71;#

%7# 6eich D- 0ennett4guerrero E- 0odian CA- 8ossain 5- >infree >- $rol M#
*ntraoperative ,ach!cardia and 8!pertension Are *ndependentl! Associated
"ith Adverse :utcome in Boncardiac 5urger! of ong Duration# Anesth#
Analg# 2&&2P;/'2):27317#
%7# 0i9=er I0- van $lei >A- Cergou"e S- Eleveld DI- van >olfs"in=el - Moons
$2M- et al# *ntraoperative h!potension and (4!ear mortalit! after noncardiac
surger!# Anesthesiolog! 2&&; DecP((('%):(2(712%#
%;# Mon= ,2- 5aini C- >eldon 0C- 5igl IC# Anesthetic management and one4!ear
mortalit! after noncardiac surger!# Anesth# Analg# 2&&/ Ian(&&'():.1(&#

7&# >alsh M- Devereaux P- 6odseth 6B- 6elationship bet"een *ntraoperative
Mean Arterial Pressure and Clinical :utcomes after Boncardiac 5urger!#
Anesthesiolog!# 2&(3P((;'3):/&71(/#

7(# $han <- Gllah 8# Pharmacological agents for preventing morbidit! associated
"ith the haemod!namic response to tracheal intubation ' 6evie" ) 5GMMA6S
:< <*BD*B25 <:6 ,8E MA*B C:MPA6*5:B# Cochrane Database 5!st#
6ev# 2&(3P'7)#

72# Pharmacolog! for Anaesthesia and *ntensive care- 3
rd
edition-,#E Pec=-5#A 8ill
73# 5undar- A-5- $odali- 6- 5ulaiman- 5# ,he effects of preemptive pregabalin on
attenuation of stress response to endotracheal intubation and opioid4sparing
Page 2% of 27
effect in patients undergoing off4pump coronar! arter! b!pass grafting# Annals
of cardiac anaesthesia 2&(2-(/ '() (742/
Page 27 of 27