Anesthesia, Essays and

Researches
Anesth Essays Res. 9(3): 397-400

Effect of intravenous clonidine premedication for

the bloodless surgical field in patients undergoing
middle ear or nasal surgery: A comparison of
three different doses
1 1 1
Sarita Ramchandani, Anand Masih Lakra , Pratibha Jain Shah , Jaya Lalwani , Kamal Kishore
1
Sahare
Department of Anaesthesiology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
1. Department of Anaesthesiology and Critical Care, Pt. J.N.M. Medical College, Raipur,
Chhattisgarh, India
Corresponding author: Dr. Sarita Ramchandani, B-16, Ashiyana Phase-1, Near Vijay Nagar
Chowk, Avanti Vihar, Raipur, Chhattisgarh - 492 006, India. E-mail:
drsaritaramchandani@gmail.com
Copyright: © 2015 Anesthesia: Essays and Researches
DOI: 10.4103/0259-1162.161821
Published in print: Sep-Dec2015

Abstract
Aim:
To evaluate the effect of intravenous (IV) clonidine premedication for
the bloodless surgical field in patients undergoing middle ear or nasal
surgery comparing three different doses.

Subjects and Methods:

This prospective randomized, clinical trial was performed on 90
normotensive patients belonging to American Society of
Anesthesiologists grade I/II, aged 18–60 years, of either sex,
undergoing routine middle ear or nasal surgery. These patients were
divided into three Groups A, B, and C with 30 patients in each
according to the dose of IV clonidine used as premedicant that is 3, 4,
and 5 µg/kg, respectively. The hypotensive period commenced 10 min
after the start of surgery till the surgeon's request for no hypotension
required any longer. The target mean blood pressure for producing
bloodless surgical field was 60–70 mmHg. During the hypotensive
period, the surgeons were asked to rate the bleeding severity score on
a six-point scale from 0 (no bleeding) to 5 (severe bleeding).

Statistical Analysis Used:

ANOVA, Chi-square test, Z-test, standard deviation and P value.

Results:
IV clonidine premedication in a dose of 4 and 5 µg/kg reduces
bleeding and provides a clear field for surgery. It also reduces the
requirement of isoflurane, fentanyl, and metoprolol for controlled
hypotension. However, clonidine 5 µg/kg was not more effective than
clonidine 4 µg/kg in producing these effects rather was associated
with some side effects.

Conclusion:
IV clonidine premedication in a dose of 4 µg/kg is safe and effective
for producing a bloodless surgical field in the middle ear and nasal
surgery.

INTRODUCTION
Middle ear and nasal surgery are a delicate and time-consuming procedure
requiring a bloodless
surgical field. To achieve these hypotensive techniques are widely used
in anesthesia.[1]
Clonidine, which is widely being accepted as anesthetic adjuvant acts by a
central α2 adrenergic mechanism reducing sympathetic nervous system
output. Besides its antihypertensive effect, it
also diminishes requirements for inhaled anesthetics and enhances the
effects of sedative,
anxiolytic, and analgesic drugs,[2] decreases pressor response to laryngoscopy
and intubation,[3]
postoperative nausea, vomiting[4] and shivering.[5]

So, this study was undertaken to evaluate the effect of intravenous (IV)
clonidine premedication
for bloodless surgical field in patients undergoing middle ear or nasal surgery
in three different
doses.

SUBJECTS AND METHODS

After approval from the Institutional Ethical Committee, written informed
consent was obtained

from 90 normotensive patients (American Society of Anesthesiologists I/II), aged

18–60 years, of
either sex, undergoing routine middle ear or nasal surgery. Patients with heart
disease, porphyria,
liver or kidney dysfunction, history of allergy, obesity (weight >80 kg),
pregnant and lactating
women were excluded from the study. Patients were assigned to three groups of
30 each. Group A
received IV clonidine 3 µg/kg while Groups B and C received IV clonidine 4
µg/kg and 5 µg/kg
respectively, 15 min prior to induction of anesthesia. Two separate IV
access were secured.

Intraoperative monitoring was done through electrocardiograph, pulse-

oximeter for saturation (SpO2), noninvasive blood pressure monitor, and

capnograph for measuring end-tidal carbondioxide (EtCO 2) using Philips

MP30 monitor. Patients were premedicated with IV ranitidine 50 mg,
ondansetron 4 mg, midazolam 1 mg along with IV clonidine 3, 4, and 5
µg/kg according to group assigned. Following preoxygenation for 3 min,
anesthesia was induced with IV fentanyl 2 µg/kg and thiopentone 5 mg/kg.
Tracheal intubation was facilitated with suxamethonium 2 mg/kg.
Anesthesia was maintained with O2 and N2O 50:50, isoflurane up to 1.5
Vol% to maintain

EtCO2 between 30 and 40 mmHg. Atracurium 0.5 mg/kg bolus followed by

0.5 mg/kg/h infusion was administered to maintain neuromuscular blocked.
Fluid replacement was based on 4.2.1 rule. To aid in achieving a bloodless
surgical field, the patients were placed in a 15° flower position, and the

surgeons were asked to inject 1% lidocaine with epinephrine 1:100,000

solution at the surgical site before tissue dissection.

The surgical time was defined as "time from the first infiltration of local
anesthetic to the completion of mucosal or skin closure". The
hypotensive period commenced 10 min after the start of surgery till the
surgeon's request for no hypotension required any longer. The
hemodynamic endpoint of anesthetic management was the
maintenance of mean blood pressure (MBP) at 60–70 mmHg for
producing bloodless surgical field. Direct control of MBP was attained
with inspired concentration increments of isoflurane up to maximum of
1.5 Vol % as needed. After 10 min if it was unsuccessful, IV fentanyl 1
µg/kg was added. If both the drugs failed to provide the desirable
hypotension, IV metoprolol 0.5 mg was given and repeated as required
to a maximum dose of 5 mg. If MBP decreased to <50 mmHg,
isoflurane was reduced by 0.25%, to a maximum of 0.5%. If
hypotension still persisted, a fluid bolus of 250 ml was infused over 15
min and was repeated as necessary.

On completion of surgery, nitrous oxide and isoflurane were

discontinued, and lungs were ventilated with 100% oxygen. Residual
neuromuscular blockade was antagonized with neostigmine 2.5 mg

and glycopyrrolate 0.5 mg and trachea were extubated following usual

extubation criteria. Heart rate (HR), systolic blood pressure (SBP),

diastolic blood pressure (DBP), MBP, SpO 2, and EtCO2 were recorded
before

premedication, baseline value, just after premedication, 5 min after

premedication, 10 min after premedication, during laryngoscopy and
intubation, 3 min after laryngoscopy and intubation, 5 min after
laryngoscopy and intubation, every 5 min interval till first 30 min,
thereafter at every 10 min interval throughout the surgery.

During the hypotensive period, the surgeons were asked every 15 min
to rate the bleeding severity

score according to the six-point scoring scale:[6]

0 - No bleeding
1 - Slight bleeding; no suctioning of blood required
2 - Slight bleeding; occasional suctioning required Surgical field not
threatened

3 - Slight bleeding; frequent suctioning required Bleeding

threatened surgical field a few seconds after suction was removed
4 - Moderate bleeding; frequent suctioning required Bleeding
threatened surgical field directly after suction was removed,
5 - Severe bleeding; constant suctioning required Bleeding
appeared faster than could be removed by suction
Surgical field severely threatened and surgery not possible.

Isoflurane, fentanyl and metoprolol requirement, duration of surgery

and hypotensive period and side effects like bradycardia (defined as
HR ≤50 bpm), inadvertent hypotension (defined as mean arterial
pressure <50 mmHg) if any, were observed, recorded, and treated
accordingly.

RESULTS

All the three groups were comparable with respect to age, weight, sex,
type of surgeries, duration of surgery, and hypotensive period [Tables
1–3].

Table 1. Patient characteristics (mean±SD)

Table 2. Type of surgeries in different groups

(number [
Table 3. Total duration of surgery and
hypotensive period in different groups (mean±SD)
The most commonly performed surgery in all the three
groups was rhinosporidiosis excision [Table 2].

The groups were comparable as regards to baseline

hemodynamic variables as well.

In inter-group comparison, significant fall in mean HR, SBP,

DBP and MBP was observed in patients of Groups B and C
as compared to Group A (P < 0.05).

The number of patients with bleeding severity score of 1

was significantly more in Groups B (37%) and C (40%) as
compared to Group A (17%)

[Table 4].

Table 4. Bleeding severity score (number [%])

Number of patients with bleeding severity score of 3 and 4

were significantly lesser in Groups B (13%) and C (10%) as
compared to Group A (36%) [Table 4].

In none of the patients of any group, bleeding severity score of 0 or

5 was observed [Table 4].
Mean isoflurane requirement was significantly more (P < 0.001)
in Group A (1.003 ± 0.28 Vol%) as compared to Group B (0.69 ±
0.23 Vol%) and C (0.68 ± 0.18 Vol%)

[Table 5].

Table 5. Isoflurane, fentanyl and metoprolol

requirement

Additional dose of fentanyl was required by 37% patients of

Group A as compared to 13% and 10% patients of Groups
B and C respectively (P < 0.01) [Table 5].

Metoprolol was required by 17% patients of Group A,

whereas none of the patients in Groups B and C required
metoprolol (P < 0.05) [Table 5].

Incidence of side effects (transient bradycardia and

xerostomia) was significantly more Group C as compared to
Groups A and B. Inadvertent hypotension was not observed in
any of the patient among the three groups
[Table 6].

Table 6. Side effects (number [%])

DISCUSSION
In our study, significant fall in mean HR, SBP, DBP, and MBP
was observed in patients receiving clonidine 4 and 5 µg/kg as
compared to 3 µg/kg. These findings were similar to the
findings of Lee et al.,[1] Welfringer et al.,[7] Nishina et al.,[8]
and Kerdawy et al.[9]

The decrease in HR after clonidine administration is due

to the reduction of the sympathetic outflow along with the
simultaneous increase of parasympathetic tone of central
origin and influence of clonidine on neurons which
receive baroreceptor afferents.[10]

Clonidine interacts with catecholaminergic neuronal system,

which modulates tonic and phasic BP control and reduces the
release of norepinephrine from nerve endings both centrally and
peripherally causing a reduction in arterial pressure.[11]
The effects of clonidine on hemodynamic variables are
dose-related and increasing the dose to more than 4 µg/kg
dose not further enhance efficacy.[12]

Number of patients with bleeding severity score of 3 and 4 were

significantly lesser in 4 µg/kg and 5 µg/kg group as compared to
3 µg/kg group. These findings were similar to the findings of
Jabalameli et al.[6] and Welfringer et al.[7] It may be due to
hemodynamic attenuation with clonidine, as diminished
sympathetic outflow results from central α 2 adrenoceptor
stimulation mean±SD or n [%])

thus reducing bleeding.

Isoflurane, fentanyl, and metoprolol requirement were

significantly less in patients receiving clonidine 4 µg/kg and 5
µg/kg as compared to 3 µg/kg. These findings were similar to
the findings of Jabalameli et al.,[6] El-Kerdawy et al.,[9] Howie
et al.[13] and Hackmann et al.[14] This may be due to
pharmacological properties of clonidine including analgesic and
antihypertensive effects.

Transient bradycardia was significantly more in patients receiving

clonidine 5 µg/kg as compared to other two groups. This finding
was similar to the finding of Welfringer et al.[7]

CONCLUSION
IV clonidine 4 µg/kg and 5 µg/kg significantly reduce bleeding
and provides a clear field for surgery. It also reduces the
requirement of isoflurane, fentanyl, and metoprolol for controlled
hypotension. However, clonidine 5 µg/kg was not more effective
than clonidine 4 µg/kg in producing these effects rather was
associated with some side effects.

Hence, we conclude, that the use of intravenous clonidine

premedication in a dose of 4 µg/kg is safe and effective for
producing a bloodless surgical field in middle ear and nasal
surgery without any significant side effects.

Financial support and sponsorship

Nil.

Conflicts of interest
There are no conflicts of interest.

Articles from Anesthesia, Essays and Researches are

provided here courtesy of Medknow Publications

PMC Copyright Notice

The articles available from the PMC site are protected by copyright, even though
access is free. Copyright is held by the respective authors or publishers who
provide these articles to PMC. Users of PMC are responsible for complying with
the terms and conditions defined by the copyright hold er. Users should assume
that standard copyright protection applies to articles in PMC, unless an article
contains an explicit license statement that gives a user additional reuse or
redistribution rights. PMC does not allow automated/bulk downloading of articles
that have standard copyright protection.

See the copyright notice on the PMC site,

https://www.ncbi.nlm.nih.gov/pmc/about/copyright/, for further details and specific
exceptions.
 REFERENCES
1. Lee J, Lovell AT, Parry MG, Glaisyer HR, Bromley LM, authors. I.v. clonidine: Does it work as a
hypotensive agent with inhalation anaesthesia? Br J Anaesth. 1999;82:639–40. [PubMed]
2. Bloor BC, Flacke WE, authors. Reduction in halothane anesthetic requirement by clonidine, an alpha-
adrenergic agonist. Anesth Analg. 1982;61:741–5. [PubMed]
3. Mikawa K, Nishina K, Maekawa N, Takao Y, Asano M, Obara H, authors. Attenuation of the
catecholamine response to tracheal intubation with oral clonidine in children. Can J Anaesth.
1995;42:869–74. [PubMed]
4. Handa F, Fujii Y, authors. The efficacy of oral clonidine premedication in the prevention of
postoperative vomiting in children following strabismus surgery. Paediatr Anaesth. 2001;11:71–4.
[PubMed]
5. Mao CC, Tsou MY, Chia YY, Chow LH, Chan KH, Lee TY, authors. Pre-anesthetic oral clonidine is
effective to prevent post-spinal shivering. Acta Anaesthesiol Sin. 1998;36:137–42. [PubMed]
6. Jabalameli M, Hashemi SM, Soltani HA, Hashemi SJ, authors. Oral clonidine premedication
decreases intraoperative bleeding in patients undergoing endoscopic sinus surgery. J Res Med Sci.
2005;I:25–30
7. Welfringer P, Manel J, Garric J, authors. Clonidine premedication and isoflurane anesthesia to reduce
bleeding in otologic surgery. Ann Fr Anesth Reanim. 1992;11:125–31. [PubMed]
8. Nishina K, Mikawa K, Maekawa N, Obara H, authors. The efficacy of clonidine for reducing
perioperative haemodynamic changes and volatile anaesthetic requirements in children. Acta
Anaesthesiol Scand. 1996;40:746–51. [PubMed]
9. El-Kerdawy HM, Zalingen EE, Bovill JG, authors. The influence of the alpha2-adrenoceptor agonist,
clonidine, on the EEG and on the MAC of isoflurane. Eur J Anaesthesiol. 2000;17:105–10. [PubMed]
10. Kumar A, Bose S, Bhattacharya A, Tandon OP, Kundra P, authors. Oral clonidine premedication for
elderly patients undergoing intraocular surgery. Acta Anaesthesiol Scand. 1992;36:159–64.
[PubMed]
11. Raval DL, Mehta MK, authors. Oral clonidine premedication for attenuation of haemodynamic response
to laryngoscopy and intubation. Indian J Anaesth. 2002;46:124–9
12. Kulka PJ, Tryba M, Zenz M, authors. Dose-response effects of intravenous clonidine on stress response
during induction of anesthesia in coronary artery bypass graft patients. Anesth Analg. 1995;80:263–8.
[PubMed]

13. Howie MB, Hiestand DC, Jopling MW, Romanelli VA, Kelly WB, McSweeney TD, authors. Effect of oral
clonidine premedication on anesthetic requirement, hormonal response, hemodynamics, and recovery
in coronary artery bypass graft surgery patients. J Clin Anesth. 1996;8:263–72. [PubMed]

14. Hackmann T, Friesen M, Allen S, Precious DS, authors. Clonidine facilitates controlled
hypotension in adolescent children. Anesth Analg. 2003;96:976–81. [PubMed]
Table 1.
Patient characteristics (mean±SD)

Table 2.
Type of surgeries in different groups
(number [%])

Table 3.
Total duration of surgery and
hypotensive period in different
groups (mean±SD)
Table 4.
Bleeding severity score
(number [%])

Table 5.
Isoflurane, fentanyl and
metoprolol requirement
(mean±SD or n [%])

Table 6.
Side effects (number [%])