Narayana Medical Journal Volume-8 | Issue-2 | July - December 2019
Sai Sudha L1, Krishna Chaitanya K2*
1Postgraduate Student, 2 Professor
Department of Anaesthesiology & Critical Care, Narayana Medical College, Nellore (AP), India.
ORIGINAL ARTICLE
* Corresponding author
Email ID: [email protected]
http://dx.doi.org/105455/nmj/00000169
ABSTRACT
Objective: To compare the anaesthetic effects of a 3-drug mixture - IV Magnesium sulphate, IV Dexamethasone,
IV Loxicard ; and IV Dexmedetomidine in suppressing the hemodynamic stress response to laryngoscopy and endotracheal
intubation.
Materials and Methods: 60 patients were divided into two equal groups of 30 in each group were enrolled in
this study. GROUP M - received 1g MgSO4, 8mg dexamethasone, 1.5mg/kg Loxicard in 100ml NS given over 10mins
(n=30) GROUP D - received 1mcg/kg dexmedetomidine in 100ml NS given over 10 mins (n=30) ; prior to induction of
anaesthesia. Both the groups were observed for changes in hemodynamic parameters like HR, SBP, DBP at 0, 1, 3, 5, 10
minutes after laryngoscopy and intubation.
Results: Comparison of both the groups reveals that HR response post intubation was better attenuated with
dexmedetomidine with statistically significant p values at all time intervals. Attenuation of blood pressure with dexmedetomidine
at 0,1 min post intubation had statistically significant p values (SBP at 0min(p-0.003) ,1 min(p-0.01) and DBP at 0min(p-
0.04), 1min(p-0.04) , whereas there was no statistically significant difference in blood pressure at 3,5,10 minutes post intubation
between both the groups.
Conclusion: The increase in heart rate was better attenuated with dexmedetomidine and blood pressure was as
effectively attenuated with the 3-drug mixture when compared to dexmedetomidine. Hence, this mixture can be used as an
effective and safe alternative to dexmedetomidine.
Keywords: Stress response, Dexmedetomidine, 3-drug mixture, heart rate, blood pressure, laryngoscopy, intubation.
Stress Response During Laryngoscopy
and Endotracheal Intubation
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Introduction
Laryngoscopy and endotracheal intubation provokes
sympathetic stimulation which can result in tachycardia and
hypertension, due to an increase in the plasma concentration
of catecholamines(1). The longer the duration and number
of failed attempts , severe is the haemodynamic stress
response. The elevation in arterial blood pressure generally
starts within seconds of laryngoscopy, peaks in 1-2 min and
returns to baseline levels within 5 to 10 mins. This
cardiovascular response could be hazarduous in patients with
hypertension, myocardial ischemia and cerebrovascular
disease (2).
Common factors precipitating this pressor response are
lighter planes of anaesthesia, anatomically difficult view,
greater force used to displace the tongue, prolonged time
and multiple attempts during laryngoscopy and intubation
and additional stimulation caused by endotracheal tube
placement alongwith cuff inflation(3).
Several strategies have been tried to obtund the stress
response following laryngoscopy and endotracheal
Intubation like local anaesthetics, intravenous opioids, ?
blockers, ?2 adrenergic agonists, vasodilators, magnesium
or by increasing volatile anaesthetic concentrations(4). No
single agent has been established as the most appropriate
for this purpose.
Lignocaine is a synthetic amide (-NHCO-) local anaesthetic.
It blocks the sodium channels in the cell membranes of the
heart. Intravenous lignocaine blunts the rise in heart rate
and blood pressure; the possible mechanism being a direct
myocardial depressant effect(5), a peripheral vasodilating
effect and an effect on synaptic transmission.
Magnesium sulfate plays a role in attenuating the stress
reponse because of its inhibitory action on the release of
catecholamines. Its anesthetic and analgesic effects are due
to its actions as an antagonist of N-methyl-D- aspartate
(NMDA) receptors(6) in the central nervous system.
Dexamethasone, a synthetic glucocorticoid decreases basal
and stress-elevated levels of the pituitary hormone ACTH.
Dexamethasone inhibits the release of ACTH via an action
on HPA axis.It also has anti inflammatory and antiemetic
effects.
Dexmedetomidine, a highly selective 2 adreno-receptor
agonist decreases the sympathetic outflow(7) and
noradrenergic activity thereby counteracting haemodynamic
fluctuations associated with sympathetic stimulation
occurring at the time of intubation(8).
This study was undertaken to compare the anaesthetic effects
of a 3-drug mixture - Magnesium sulphate, Dexamethasone
and Loxicard to Dexmedetomidine in suppressing the
hemodynamic stress response to laryngoscopy and
endotracheal intubation.
Materials and Methods
This prospective randomized, double blinded control study
was conducted in sixty patients undergoing elective surgical
procedures under general anaesthesia with endotracheal
intubation. After getting institutional ethical committee
approval, the patients were informed of the study and written
consent was obtained.
Inclusion Criteria
Patients in the age group of 18 to 60 years
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ASA Physical status I, II and III
Weight between 50 to 80 kgs
Modified Mallampati Grade III and IV were included in
the study.
Exclusion Criteria
The patients with ischemic heart disease, cerebrovascular
disease, asthma, pregnancy, full stomach and emergency
surgery were excluded from the study.
All the patients were assessed preoperatively and
Premedicated with Tab. Alprazolam 0.5mg orally on the
night before surgery. In preoperative room, baseline
parameters were recorded. Intravenous access was secured
and all patients were hydrated with 500ml of Ringer's lactate.
60 patients were randomly divided by computer generated
randomization into two groups of 30 patients in each group.
Group M - received 1g MgSO4, 8mg dexamethasone,
1.5mg/kg Loxicard in 100ml NS given over 10mins (n=30)
Group D - received 1mcg/kg dexmedetomidine in 100ml
NS given over 10 mins (n=30) ; prior to induction of
anaesthesia.
The anaesthesiologist, who was not aware of the groups,
administered the study drug and recorded the vital
parameters HR,SBP and DBP. After preoxygenation with
100% oxygen for 3 minutes, patients were induced with
Inj. Midazolam 1mg IV, Inj Fentanyl 2mcg/kg IV, Inj
Propofol 2 mg/kg IV, followed by Inj. Atracurium 0.5mg/
kg IV, after confirming a lack of response to voice and a
loss of the eyelash reflex. Laryngoscopy and intubation was
performed by another anaesthesiologist who was also
blinded to the drug given. After 3 minutes of ventilation
with 100% oxygen, endotracheal intubation was performed
with an appropriate size cuffed endotracheal tube. No
surgical stimulation was allowed for 10 minutes after
intubation.HR, SBP, DBP were noted at 0,1,3,5 and 10
minutes after intubation. Anaesthesia was maintained with
50% oxygen, 50% air, Sevoflurane 2% and Inj. Atracurium
0.1mg/kg. At the end of the surgery, patients were reversed
with Inj. Neostigmine 0.05mg/kg and Glycopyrrolate
0.01mg/kg.
Statistical Analysis
Statistical analysis was performed using SPSS version 20.
Continuous variables were expressed as Mean and Standard
Deviation. Categorical variables were expressed as numbers
and percentages. Intergroup comparison was done using
Student's T test and Chi-square test. P value <0.05 was
considered as statistically significant.
Results
There was no statistically significant difference in the
demographic parameters in both the groups (Table 1).
Group D Group M
Age ( in years) 36.18±8.56 34.27±8.43
Gender (M/F) M-11, F-19 M-9, F-21
Table 1:Demographic parameters in the both groups.
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Baseline parameters were comparable in both the groups
with statistically no significant difference.
Both the groups controlled the heart rate and blood pressure
to laryngoscopy and endotracheal intubation effectively.
Comparison of Heart Rate between both the groups reveals
that; the decrease in heart rate was more with Group D when
compared to Group M. Heart rate values were statistically
significant at all time intervals in Group D as compared to
Group M (p<0.05).
At pre induction, the mean value for HR in Group D was
97.6 and in Group M was 94.8. At 0 minute that is
immediately after intubation, mean HR in Group D was 80.6
and in Group M were 84.13. At 1 minute, HR in Group D is
78.7 and in group-M is 86. At 3 minutes, HR in Group D
was 77.06 and in Group M was 85. At 5 minutes, HR in
Group D was 74.08 and in Group M was 84. At 10 minutes,
HR in Group D was 74.8 and in Group M was 83.
Table 2: Heart rate recordings in both the groups
Fig 1. Heart Rate
Comparison of Systolic blood pressure response between
both the groups reveals that there was a statistically
significant difference at 0 and 1 minute after intubation in
Group D (SBP at 0min(p-0.003) ,1 min(p-0.01) ) when
compared to Group M. At other time intervals; 3,5,10
minutes after intubation, the systolic blood pressure was
comparable between both the groups with no statistically
significant difference.
At Pre induction, the mean value for SBP in Group D was
117 and in Group M was 132.9. At 0 minute that is
immediately after intubation, mean SBP in Group D was
99 and in Group M was 110.4. At 1 minute, SBP in Group
D is 105 and in Group M is 111.7. At 3 minutes, SBP in
Group D was 110.5 and in Group M was 113. At 5minutes,
SBP in Group D was 115 and in Group M was 111. At 10
minutes, SBP in Group D was 115.3 and in Group M was
113.
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Table 3: Systolic blood pressure recordings in both the
groups.
Fig 2. Systolic Blood pressure
Comparison of Diastolic blood pressure between both the
groups reveals that there was a statistically significant
difference at 0 and 1 minute after intubation in Group D
(DBP at 0min(p-0.04), 1min(p-0.04) ) when compared to
Group M. At other time intervals; 3,5,10 minutes after
intubation, the diastolic blood pressure was comparable
between both the groups with no statistically significant
difference.
At Pre induction, the mean value for DBP in Group D was
84.2 and in Group M was 83.3. At 0 minute that is
immediately after intubation, mean DBP in Group D was
78.06 and in Group M was 85.26. At 1 minute, DBP in
Group D is 70.7 and in Group M is 76.2. At 3 minutes,
DBP in Group D was 77 and in Group M was 75.5. At
5minutes, DBP in Group D was 77.4 and in Group M was
73.8. At 10 minutes, DBP in Group D was 72.4 and in Group
M was 74.8.
Table 4: Diastolic blood pressure in both the groups.
Fig 3. Diastolic Blood pressure
Discussion
Laryngoscopy and endotracheal intubation during general
anaesthesia results in a marked sympathetic response with
a transient increase in Heart Rate and arterial blood pressure
probably as a result of intense sympathetic nervous system
stimulation(9) . In patients who are at risk of developing
increased intracranial pressure, arterial hypertension and
myocardial ischemia, these changes may be life threatening.
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They may lead to cerebral haemorrhage, left ventricular
failure and life threatening cardiac arrhythmias (10). If no
specific measures are taken to prevent hemodynamic
response, reflex changes in the cardiovascular system lead
to an average increase in blood pressure by 40-50% and
20% increase in heart rate.
Commonly used drugs are Beta blockers, alpha-2 agonists,
opioids, Magnesium Sulphate and Lignocaine attenuate
these potentially harmful cardiovascular reactions during
laryngoscopy and intubation.Various other techniques were
also tried to attenuate the cardiovascular response , one of
them being deep inhalational anaesthesia, which may cause
intracranial hypertension. Potent vasodilator drugs need
larger doses to attenuate arterial blood pressure but they
may cause reflex tachycardia which is not desirable while
others depress the myocardium in patients with preexisting
left ventricular dysfunction or those receiving beta
adrenergic antagonist. These effects are not desirable and
limit their usefulness.
Various studies have shown that intravenous lignocaine is
effective in attenuating the arterial hypertension and
tachycardia in response to endotracheal intubation.
Splinter & Cervenko (11) demonstrated that 1.5mg/kg of
I.V. Lignocaine could attenuate the increase in systolic blood
pressure, mean arterial pressure and rate pressure product
associated with endotracheal intubation.
Calcium exerts a major role in stimulus-response
relationship, including the release of catecholamines from
the adrenal gland and adrenergic nerve terminals in response
to sympathetic stimulation. Because Magnesium competes
with calcium for membrane channels, it has been described
as the physiological calcium antagonist (12) and can modify
many calcium mediated responses.
The ability of magnesium ion in inhibiting the release of
catecholamines has long been recognized, hence Magnesium
Sulphate is considered for use in laryngoscopy and
intubation to minimize unwanted cardiovascular responses
(13).
Dexamethasone, a synthetic glucocorticoid decreases basal
and stress-elevated levels of the pituitary hormone ACTH.
Dexamethasone inhibits the release of ACTH via an action
on HPA axis (14). It also has anti inflammatory and
antiemetic effects. It is usually used prior to induction of
anaesthesia. It has been used for many purposes like intra-
op and post-op shivering, to reduce the airway edema after
a difficult intubation, for prevention of PONV, used in
peripheral nerve blocks to prolong the duration of blockade
and to potentiate the effect. Razavizadeh et.al has advocated
the use of dexamethasone in epidural anaesthesia for post
operative analgesia (15).
Hence, in this study, we have compared the additive
anaesthetic effects of 3 drugs viz. Magnesium Sulphate,
Lignocaine and Dexamethasone, and to assess the usefulness
of dexamethasone in potentiating the effect of the other two
drugs for attenuation of the stress response during
endotracheal intubation.
Dexmedetomidine, a highly selective alpha 2-
adrenoreceptor agonist offers a unique pharmacological
profile with sedation, sympatholysis, analgesia,
cardiovascular stability and with great advantage of
respiratory depression sparing effect.
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Dexmedetomidine by activating pre and post-synaptic alpha
2 receptors of sympathetic system produces vasodilatation;
and also by acting on post-synaptic alpha 2 receptors of
vascular smooth muscle cells it produces vasoconstriction.
Thus it shows a biphasic, dose dependent response on blood
pressure and heart rate, characterized by an initial short term
increase in BP followed by a longer lasting reduction in BP
and HR. It produces sympatholysis by stimulating alpha 2
adrenergic inhibitory neurons in medullary vasomotor centre
(16) which is manifested as peripheral vasodilatation and
decrease in blood pressure, heart rate and cardiac output.
Smitha et al observed that dexmedetomidine 1 ?g/kg was
more effective in controlling haemodynamic responses to
tracheal intubation (17).
Few authors (18) have observed increased sedation levels
and need for oxygen supplementation with
dexmedetomidine at a dose of 1mcg/kg.
It has been shown to cause irregular breathing with episodes
of apnoea, especially at a dose of 2.0 ?g/kg (19).Increased
incidence of adverse effects such as bradycardia and
hypotension (20) have also been reported.
Dexmedetomidine is better avoided in elderly patients,
patients with pre-existing bradycardia or heart blocks. In
such cases, the combination of the 3-drug mixture can be
used safely for all patients and for any kind of surgery.
Conclusion
The increase in heart rate was better attenuated with
dexmedetomidine and blood pressure was as effectively
attenuated with the 3-drug mixture when compared to
dexmedetomidine. Hence, this mixture can be used as an
effective and safe alternative to dexmedetomidine.
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