Single-dose dexmedetomidine attenuates airway and circulatory reflexes during extubation.

Abstract

The alpha agonist dexmedetomidine, a sedative and analgesic, reduces heart rate and blood pressure dose-dependently. We investigated whether it also has the ability to attenuate airway and circulatory reflexes during emergence from anaesthesia.
Sixty ASA I-III patients received a standard anaesthetic. Five minutes before the end of surgery, they were randomly allocated to receive either dexmedetomidine 0.5 microg/kg (Group D) (n=30) or saline placebo (Group P) (n=30) intravenously (i.v.) over 60 s in a double-blind design. The blinded anaesthetist awoke all the patients, and the number of coughs per patient was continuously monitored for 15 min after extubation; coughing was evaluated on a 4-point scale. Any laryngospasm, bronchospasm or desaturation was recorded. Heart rate (HR) and systolic and diastolic blood pressure (SAP, DAP) were measured before, during and after tracheal extubation. The time from tracheal extubation and emergence from anaesthesia were recorded.
Median coughing scores were 1 (1-3) in Group D and 2 (1-4) in Group P (P<0.05), but there were no differences between the groups in the incidence of breath holding or desaturation. HR, SAP and DAP increased at extubation in both groups (P<0.05), but the increase was less significant with dexmedetomidine. The time from tracheal extubation and emergence from anaesthesia were similar in both groups.
These findings suggest that a single-dose bolus injection of dexmedetomidine before tracheal extubation attenuates airway-circulatory reflexes during extubation.

Full text

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Single-dose dexmedetomidine attenuates airway and
circulatory reflexes during extubation
G. GULER, A. AKIN, Z. TOSUN, E. ESKITASCOGLU, A. MIZRAK and A. BOYACI
Department of Anesthesiology, Erciyes University, Medical Faculty, Kayseri, Turkey
Background: The alpha agonist dexmedetomidine, a sedative
and analgesic, reduces heart rate and blood pressure dose-
dependently. We investigated whether it also has the ability to
attenuate airway and circulatory reflexes during emergence
from anaesthesia.
Methods: Sixty ASA I—III patients received a standard anaes-
thetic. Five minutes before the end of surgery, they were
randomly allocated to receive either dexmedetomidine 0.5 mg/kg
(Group D) (n ¼ 30) or saline placebo (Group P) (n ¼ 30) intra-
venously (i.v.) over 60 s in a double-blind design. The blinded
anaesthetist awoke all the patients, and the number of coughs
per patient was continuously monitored for 15 min after extuba-
tion; coughing was evaluated on a 4-point scale. Any laryngos-
pasm, bronchospasm or desaturation was recorded. Heart rate
(HR) and systolic and diastolic blood pressure (SAP, DAP) were
measured before, during and after tracheal extubation. The time
from tracheal extubation and emergence from anaesthesia were
recorded.
Results: Median coughing scores were 1 (1—3) in Group D and 2
(1—4) in Group P (P < 0.05), but there were no differences
between the groups in the incidence of breath holding or desa-
turation. HR, SAP and DAP increased at extubation in both
groups (P < 0.05), but the increase was less significant with
dexmedetomidine. The time from tracheal extubation and emer-
gence from anaesthesia were similar in both groups.
Conclusion: These findings suggest that a single-dose bolus
injection of dexmedetomidine before tracheal extubation attenu-
ates airway-circulatory reflexes during extubation.
Accepted for publication 4 April 2005
Key words: dexmedetomidine; cardiovascularsystem; respon-
ses; tracheal; extubation; intraocular surgery.
#Acta Anaesthesiologica Scandinavica 49 (2005)
S
yngospasm (1). Further, it is particularly important
to avoid increases in heart rate and blood pressure
in intraocular-, neuro-, and vascular surgery. Many
techniques and drugs have been proposed for the
attenuation of cardiovascular and airway responses,
but none have been completely successful (2—5).
Dexmedetomidine, a potent alpha adrenoceptor
agonist which dose-dependently reduces arterial
blood pressure and heart rate (6), decreases the
haemodynamic and plasma catecholamine response
to intubation and extubation (7—9). Extubation at
light levels of anaesthesia/sedation can stimulate
reflex responses via tracheal and laryngeal irritation
(10). However, two studies on the effects of dexme-
detomidine during extubation failed to mention its
effects on coughing and other airway reflexes (8, 9).
Opiates and local anaesthetics have been used to
reduce these reflexes (11—13), but both techniques
have limitations. Dexmedetomidine is used for
sedation and analgesia in intensive care units,
MOOTH extubation requires the absence of strain-
ing, movement, coughing, breath holding or lar-
where its relative lack of effect on respiration is an
advantage (14); it is thus theoretically appropriate
for reducing airway and circulatory reflexes during
emergence from anaesthesia. In this study, we
aimed to investigate its effects during extubation
on coughing, airway reflexes and haemodynamics.
Patients and methods
After obtaining approval from the Local Research
Ethics Committee, and written informed consent, we
studied 60 ASA I—III patients, aged 40—75 years,
scheduled for intraocular surgery. Patients with
asthma, dysrhythmia, congestive heart failure, and
dementia were excluded. Heart rate (HR), peripheral
oxygen saturation(SpO2),
pressure and end-tidal carbon dioxide (ETCO2) were
monitored (DatexEngstrom
Monitor; Helsinki, Finland). All patients were preme-
dicated with atropine. Anaesthesia was induced with
4—5 mg/kg thiopental and 1 mg/kg fentanyl. Vecu-
ronium (0.1 mg/kg) was used for neuromuscular
non-invasiveblood
AS/3 Anesthesia
Acta Anaesthesiol Scand 2005; 49: 1088—1091
Printed in UK. All rights reserved
Copyright#Acta Anaesthesiol Scand 2005
ACTA ANAESTHESIOLOGICA SCANDINAVICA
doi: 10.1111/j.1399-6576.2005.00780.x
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relaxation
performed (8 or 8.5 mm for males, 7 or 7.5 mm for
female patients, high-volume/low pressure CURITY
endotracheal tubes: cuffed tracheal tube Murphy eye,
Sampran, Thailand; Tyco Healthcare Switzerland Ltd,
Wollerau, Switzerland). Anaesthesia was maintained
with sevoflurane (1—2% end-tidal concentration) and
66% nitrous oxide in oxygen using mechanical venti-
lation. End-tidal carbon dioxide partial pressure was
maintained at 4.2—5.5 kPa. No additional opioid was
given after induction. Patients were allocated ran-
domly to one of two groups in a double-blind manner.
Five minutes before the end of the surgery, patients in
group D (n ¼ 30) received 0.5 mg/kg dexmedetomi-
dine in 10 ml of isotonic solution, and patients in
group P (n ¼ 30) received 10 ml of isotonic solution,
both given over 60 s. Sevoflurane and nitrous oxide
werestoppedattheendoftheoperationand0.05 mg/
kg neostigmine and 0.02 mg/kg atropine were given
for neuromuscular block reversal. Oropharyngeal
secretions were aspirated immediately prior to extu-
bation, which was performed when the patients could
breathe spontaneously. After tracheal extubation,
100% oxygen was given via a facemask for 5 min.
The same anaesthetist, blinded to the drug given,
woke all the patients. Coughing after extubation was
assessed with a 4-point scale: 1 ¼ no coughing,
2 ¼ minimal coughing (once or twice), 3 ¼ moderate
coughing (3—4 times) and 4 ¼ severe coughing (5 or
more times). A decrease of peripheral arterial oxygen
saturation >5% from baseline was defined as
desaturation, and holding breath for 20 s or more as
breath holding. Any laryngospasm, bronchospasm
and desaturation were recorded.
HR,SAP,andDAPvalueswererecordedbeforeand
1, 3 and 5 min afterdrug administration, during extu-
bation, and at 1, 3, 5 and 10 min after extubation.
Extubation time (defined as the time between the
discontinuation of inhalation agents and extubation),
and emergence time (between the discontinuation of
inhalation agents and verbal and motor responses to
verbalstimuli)were recorded.Arterialbloodpressure
and heart rate were maintained at between 80% and
120% of the pre-operative values by increasing or
decreasing the concentration of sevoflurane until the
end of surgery. Intravenous nitroglycerin was used to
control severe hypertension (defined as systolic value
> 180 mmHg), and beta-blockers to control tachy-
cardia (defined as HR > 100/min, lasting longer
than 3 min) not controlled by increasing the concen-
tration of inhalation agent. Ephedrine (5—10 mg
i.v. bolus) was given when hypotension (decrease in
systolic pressure > 25% from baseline, or an absolute
andendotrachealintubation was
systolic value < 90 mmHg) could not be controlled
within 3 min by increasing the fluid infusion and
decreasing gas concentrations, and atropine (0.5 mg
i.v. bolus) was given for bradycardia (HR < 45 min).
Possible adverse affects during and after the admin-
istration of dexmedetomidine and during the post-
operative period such as arrhythmia, bradycardia,
tachycardia, hypotension, hypertension, vomiting
and dry mouth were recorded.
Statistical analysis
Statistical analysis was carried out usingthe Student’s
t-test for SAP, DAP and HR differences between
groups, repeated measures ANOVA for intragroup
evaluation, and the Mann—Whitney U-test for extuba-
tion scores. Nominal data were analysed using the w2
or Fisher’s exact test. Statistical significance was
accepted as P < 0.05. Power analysis showed to
demonstrate a decrease in the incidence of coughing
on extubation with dexmedetomidine of 30% com-
pared with the control group would require 30
patients in each group, and that 24 patients in each
group would provide a power of 0.8.
Results
Patient characteristics, duration of surgery and
anaesthesia were similar in the two groups (Table 1).
Coughing and other airway events
In Group D, coughing was observed in nine patients,
six minimal and three moderate, after extubation, and
in 19 (11 minimal, five moderate, and three severe), in
Group P (P < 0.05). There were no differences in the
incidence of breath holding or desaturation between
the two groups, and no patient developed laryngos-
pasm or bronchospasm after extubation.
There were no significant differences in extuba-
tion times (Group D; 5.82 ? 2.74 min, Group P;
Table 1
Demographic data.
Group D
(n ¼ 30)
X ? SD
68 ? 3
72 ? 10
49 ? 11
40 ? 12
17 : 13
23
Group P
(n ¼ 30)
X ? SD
70 ? 6
68 ? 8
55 ? 13
44 ? 13
14 : 16
21
Age (year)
Weight (kg)
Duration of anaesthesia (min)
Duration of surgery (min)
Gender (M/F)
Smoking (%)
Effect of dexmedetomidine on extubation
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5.32 ? 3.18 min) or emergence times (Group D;
12.46 ? 5.28 min, Group P; 11.75 ? 4.17 min).
Haemodynamic results
SAP, DAP and HR increased significantly during extu-
bation in both groups (Fig. 1) (Fig. 2), but SAP was
significantly lower in group D than in Group P at all
times starting from 3 min after drug administration
(Fig. 1). DAP was similarly always lower in Group D
from 5 min after drug administration (Fig. 1).
In Group D, bradycardia occurred in one patient
and hypotension in three, within 3 min of drug
administration.Atropinewasadministeredforbrady-
cardia, hypotension was treated within 2 min by
giving fluid infusion and reducing inhalation agents;
no vasopressor was required. SAP > 180 mmHg was
observed in four patients in Group D and in eight
patients in Group P during extubation; it was treated
with a nitroglycerin infusion in one patient in Group
D and in three in Group P. In Group D, one patient
complained of a dry mouth.
Discussion
We found that the cough reflex and increase in SAP,
DAP and HR associated with emergence from anaes-
thesia were attenuated by i.v. dexmedetomidine
0.5 mg/kg. The presence of the endotracheal tube
leads to reflex responses, the most common of
which is coughing (12). Kim and Bishop (15) found
a 76% incidence of coughing during emergence.
Coughing can result in hypertension, tachycardia,
increased intraocular and intracranial pressure,
myocardial ischaemia, bronchospasm, and surgical
bleeding (16). Increases in intraocular pressure can
cause complications in intraocular surgery (17).
Several techniques have been used to elevate these
problems, such as deep extubation and use of a
laryngeal mask (1, 18), techniques which are inap-
plicable in non-fasting patients or those with gastro-
esophageal reflux disease. Intravenous opioids or
lidocaine may be beneficial, but can delay emergence
(19). Topical anaesthesia applied before intubation is
not effective (12). We found that dexmedetomidine
facilitated tolerance of the endotracheal tube and
significantly reduced coughing during extubation,
without affecting emergence time, an effect possibly
mediated via its sedative and analgesic properties.
Although the mechanisms responsible for haemo-
dynamic changes during extubation are not exactly
known, possible factors may be wound pain, emer-
gence from anaesthesia and tracheal irritation
(20, 21). Previous studies have shown a moderate
increase in blood pressure and heart rate lasting
5—15 min, although not normally constituting a
serious problem could do so in some patient groups
(22—24). Jaakola et al. (7) attenuated the increase in
heart rate and arterial blood pressure during intuba-
tion by bolus injection of 0.6 mg/kg dexmedetomidine,
which also decreased intra-operative intraocular
pressure and anaesthetic requirements. Talke et al.
(9)achieved considerable
increases in HR, BP and plasma catecholamine con-
centrations during emergence in patients who had
attenuationofthe
*
*
*
*
*
*
*
+
+
+
+
+
40
60
80
100
120
140
160
180
200
220
T1T2T3T4T5T6T7T8T9
Time
Arterial pressure (mmHg)
Group D SAP
Group P SAP
Group D DAP
Group P DAP
Fig. 1. Changes
(mean ? SD). SAP: systolic arterial pressure; DAP: diastolic
arterial pressure. *P < 0.05 SAP between groups, †P < 0.05
between groups. Measurement points; T1: before administration
of dexmedetomidine, T2: 1 min after administration of dexmedeto-
midine, T3: 3 min after administration of dexmedetomidine, T4:
5 min after administration of dexmedetomidine; T5: after tracheal
extubation, T6: 1 min after tracheal extubation, T7: 3 min after
tracheal extubation, T9: 10 min after tracheal extubation.
insystolicanddiastolicarterialpressure
*
*
*
50
60
70
80
90
100
110
T1T2T3T4T5T6T7 T8T9
Time
Heart rate (beats/min)
Group D HR
Group P HR
Fig. 2. Changes in heart rate (mean ? SD). HR: heart rate (beats/
min); *P < 0.05 HR between groups, Measurement points; T1:
before administration of dexmedetomidine, T2: 1 min after admin-
istration of dexmedetomidine, T3: 3 min after administration of
dexmedetomidine, T4: 5 min after administration of dexmedetomi-
dine; T5: after tracheal extubation, T6: 1 min after tracheal extu-
bation, T7: 3 min after tracheal extubation, T9: 10 min after
tracheal extubation.
G. Guler et al.
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undergone vascular surgery, although HR and BP
later in the post-operative period were not affected.
In that study, a dexmedetomidine infusion was
started 20 min before the induction of anaesthesia
and continued for 48 h. Intra-operative use of anaes-
thetics and post-operative use of analgesics were
unaffected. Our single dose appears to have been as
effective as the infusion at extubation.
Lawrence et al. (8) found that a single dose of
dexmedetomidine given before induction reduced
the need for anaesthetics and post-operative analge-
sics, and also attenuated
response to intubation and extubation. The discre-
pancy between this study and that of Talke et al. (9)
may be due to differences in patient groups. Further,
Lawrence et al. (8) used a large dose of dexmedeto-
midine before the induction of anaesthesia, and
hypotension and bradycardia were observed more
frequently. In our study, dexmedetomidine attenu-
ated the increase in blood pressure to a greater
degree than the increases in heart rate; there was
an increase in HR in both groups during and after
extubation. Only 1—3 min after extubation, this
increase was significantly less in the dexmedetomi-
dine group. Atropine, used with neostigmine in
order to antagonize residual block, will also have
contributed to the increase in heart rate.
In conclusion, dexmedetomidine attenuates the
airway/circulatory reflexes during emergence from
anaesthesia without prolonging recovery. We believe
that its use during emergence from anaesthesia in
intraocular surgery should be recommended.
the haemodynamic
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PippinWD,Weaver JM.
Address:
Gulen Guler
Anesteziyoloji Anabilim Dali
Erciyes Universitesi Tip Fakultesi
38039, Kayseri
Turkey
e-mail: gulen@erciyes.edu.tr
Effect of dexmedetomidine on extubation
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