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A randomized, double blind, controlled study on the effects of addition of clonidine to bupivacaine used for patients undergoing spinal anaesthesia

Authors:

Abstract

Background: Spinal anaesthesia provided by bupivacaine alone may be too short for the planned surgery. The addition of clonidine 1 µg/kg to bupivacaine provides a prolonged anaesthetic action. The aim of this randomized double-blinded controlled study was to investigate the effects of addition of low dose clonidine to hyperbaric bupivacaine 0.5%, for spinal anaesthesia in patients undergoing lower abdominal and lower limb surgeries, on analgesic efficacy, quality of block, duration of analgesia and adverse effects. Methods: Forty adult ASA Grade I and II patients of either sex posted for lower abdominal and lower extremity surgeries were randomly divided equally in to clonidine or control group. Control group received intrathecal 3.5ml of 0.5% hyperbaric bupivacaine with 0.5 ml of normal saline and Clonidine group received identical volume of intrathecal clonidine 1 µg/kg with 0.5% hyperbaric bupivacaine.
Sri Lankan Journal of Anaesthesiology
CLINICAL INVESTIGATIONS
A RANDOMIZED, DOUBLE BLIND, CONTROLLED STUDY ON THE
EFFECTS OF ADDITION OF CLONIDINE TO BUPIVACAINE USED
FOR PATIENTS UNDERGOING SPINAL ANAESTHESIA
*Bhavini Shah
1
, Ramchandra Shidhaye
1
, Devdas Divekar
1
, Mrudul Panditrao
2
; Minnu Panditrao
2
;
Chhaya Suryawanshi
2
Assistant Lecturer, Professor, Department of Anesthesiology and Critical Care, Pravara Institute of
Medical Sciences, Loni 413736 India
1
; Professor Department of Anesthesiology and Critical Care, Dr.
D.Y. Patil Medical College Pimpri, Pune 411018 India
2
*Corresponding author: rvshidhaye@yahoo.com
Key words: Intrathecal; Clonidine; Bupivacaine; Postoperative pain; Spinal anaesthesia
Background:
Spinal anaesthesia provided by bupivacaine alone may be too short for the planned surgery. The
addition of clonidine 1 µg/kg to bupivacaine provides a prolonged anaesthetic action. The aim of
this randomized double-blinded controlled study was to investigate the effects of addition of low
dose clonidine to hyperbaric bupivacaine 0.5%, for spinal anaesthesia in patients undergoing lower
abdominal and lower limb surgeries, on analgesic efficacy, quality of block, duration of analgesia
and adverse effects.
Methods:
Forty adult ASA Grade I and II patients of either sex posted for lower abdominal and lower
extremity surgeries were randomly divided equally in to clonidine or control group.
Control group received intrathecal 3.5ml of 0.5% hyperbaric bupivacaine with 0.5 ml of normal
saline and Clonidine group received identical volume of intrathecal clonidine 1 µg/kg with 0.5%
hyperbaric bupivacaine.
Results:
Average two level regression time (129.55 min) was significantly prolonged in clonidine group
than in the control group (74.5 min). (p-value < 0.01) Mean time for post operative analgesia was
significantly longer in clonidine group (8.8 hours) than in the control group (4.1 hours). (p-value <
0.01). Heart rate at 15 minute intervals compared to 2 minute intervals was significantly less in
clonidine group. ( p-value < 0.05). Bradycardia, hypotension, urinary retention and headache did
not require any therapeutic intervention
Conclusion:
Adding clonidine 1 µg/kg to intrathecal bupivacaine prolongs the duration of spinal anaesthesia
and analgesia. It is safe and is likely to be as effective as higher doses of bupivacaine without
severe adverse effects.
Spinal anaesthesia has increasingly become the
technique of choice for lower abdominal and
lower extremity surgeries due to quick onset and
effective sensory and motor blockade and ease of
administration. To overcome its disadvantage of
limited duration of anaesthesia and analgesia,
various adjuvant drugs (opioids, benzodiazepines,
ketamine, or neostigmine) have been used which
have their own side effects. In our study the α
2
-
adrenergic agonist clonidine which has the ability
17
to potentiate the effects of local anaesthetics
1-3
has
been used as an adjuvant . Unlike spinal opioids,
clonidine does not produce pruritus or respiratory
depression but prolongs the sensory blockade
2, 4
and reduces the amount or concentration of local
anaesthetic required to produce postoperative
analgesia
5, 6
. The aim of this randomized double-
blinded controlled study was to investigate the
effect of addition of clonidine to hyperbaric
bupivacaine 0.5%, for spinal anaesthesia in
patients undergoing lower abdominal and lower
limb surgeries on analgesic efficacy, quality of
block, duration of analgesia and adverse effects.
Materials and Methods
After approval from the hospital ethical
committee, this study was carried out in 40 adult
ASA Grade I and II patients of either sex posted
for lower abdominal and lower extremity
surgeries. Excluding criteria were: systemic
disorders like diabetes mellitus, hypertension,
heart disease, allergy to bupivacaine or clonidine
and all known contraindications for spinal
anaesthesia, such as spine deformity, increased
intracranial pressure, neurological disorders,
haemorrhagic diathesis, or infection at the
puncture site. A double-blind, randomized,
placebo-controlled study design with two parallel
groups was used. After valid informed written
consent selected patients were randomly allocated
to two groups by lottery method.
Clonidine group: 3.5ml Bupivacaine (0.5%) + Inj
Clonidine 1mcg/kg (Preservative free) + normal
saline to make the volume 4ml intrathecally
Control group: 3.5 ml Bupivacaine (0.5%) + 0.5
ml Normal Saline intrathecally
Both the patient and anesthesiologist were blinded
to the study solutions. Syringes were prepared
immediately before the spinal injection ensuring
the volumes at 4ml by a third person other than the
anaesthesiologist who administered the drugs
intrathecally and later on did the parameter
assessment. This third person only did the random
allocation and he knew the status of
experiment/control of the patient to unblind the
status in case of an emergency. Sedatives and
hypnotics were avoided during the pre operative
and intra operative period. Intravenous line was
secured with a 20 G cannula and all patients were
preloaded with Ringer Lactate solution at 10ml/kg.
Lumbar puncture was done in the sitting position
under aseptic conditions in the L3-L4 space with a
26G Quincke needle. Intrathecal study drug was
injected and patient was placed in the supine
position. The time at which the intrathecal
injection was completed was considered as zero.
Noninvasive arterial blood pressure, heart rate, and
oxygen saturation assessed at zero time and every
2 minutes for the first 10 minutes after spinal
injection, and thereafter, every 5 minutes during
the surgery.
The level of sensory blockade was tested by
pinprick method in midline and the motor
blockade was tested with the modified Bromage
scale used by Breen et al
7
. The time of onset and
time of peak sensory and motor block, time to
regression of sensory block by two dermatomes,
time to full recovery of motor block, level of intra
operative sedation and time to first rescue
analgesic were recorded. Hypotension, defined as
a decrease of systolic blood pressure of more than
20% from baseline, was treated with metaraminol
and bradycardia, defined as a heart rate decrease
of more than 20% from baseline was treated with
atropine. For rescue analgesia Inj tramadol 100mg
or Inj diclofenac sodium 75 mg was given.
The various data obtained, which included
different parameters measured at different time
intervals, were calculated and compared with
baseline values within each group as well as with
corresponding times among groups using
independent t test. For comparison of
complications in the two groups chi
2
test was
used. A ‘p’ value <0.05 was taken as significant.
The sample size was not calculated before the start
of the study and number of patients to be studied
in the trial was based on previous literature.
4, 8
Post-hoc power analysis was carried out for “two
segment regression time in minutesand “time for
first rescue analgesia in hours.” Estimated power
for two-sample comparison of means was 1.00.
Results
The patients’ characteristics are shown in Table I.
There is no significant difference in the two
groups. (p-value > 0.05)
18
Table I: Demographic characteristics
Parameter Clonidine group
(n=20)
Mean ± SD
Control
group (n=20)
Mean ± SD
Age (yrs) 38.15 ± 12.89 38.2 ± 11.00 *
Weight (kg) 54.3 ± 8.81 56.85 ± 7.12 *
Sex (M:F) 10 : 10 7 :13
ASA I : II 17 :3 17:3
* p-value > 0.05 ** p-value significant at
0.05; *** p-value significant at 0.01
Table II compares the time for onset and peak of
sensory and motor blockade in both groups. Time
required for onset of sensory and motor blockade
was similar in both groups. Peak sensory blockade
was delayed in clonidine group than control group,
but the time required for peak motor blockade was
similar in both groups. Average two level
regression time (129.55 min) was significantly
prolonged in clonidine group than control group
(74.5 min). (p-value < 0.01)
Mean time for post operative analgesia was
significantly longer in clonidine group (8.8 hours)
than control group (4.1hour)(p-value < 0.01)
Table II: Analysis of Sensory, Motor blockade
and Duration of analgesia
Parameter Clonidine
group (n=20)
Mean ± SD
Control group
(n=20)
Mean ± SD
Time in seconds for
onset of sensory
blockade
70.35 ± 16.56 71.05 ± 16.85 *
Time in seconds for
onset of motor
blockade
113.7 ± 28.16 118.1 ± 22.06 *
Time in minutes for
peak of sensory
blockade
5.015 ± 0.81 4.3 ± 0.78 ***
Time in minutes for
peak of motor
blockade
7.27 ± 1.63 8.25 ± 1.91 *
Two segment
regression time in
minutes
129.55 ± 14.55 74.5 ± 7.16 ***
Time for first rescue
analgesia in hours
8.8 ± 1.9 4.1 ± 0.6 ***
* p-value > 0.05 ** p-value
significant at 0.05; *** p-value significant at
0.01
Table III compares heart rates, systolic and
diastolic blood pressure in both groups at different
time intervals. Both groups are comparable
regarding systolic and diastolic blood pressure at
all time except at sixty minutes. Heart rate at 15
minutes compared to 2 minutes is significantly
less in clonidine group (p-value < 0.05). Mean
heart rate was significantly higher at the end of
surgery in control group, than in clonidine group.
(p-value < 0.01) It was more or less stable at lower
levels throughout in the clonidine group.
Table III: Analysis of heart rate, systolic and
diastolic blood pressure
2
Min
15
Min
30
Min
45
Min
60
Min
90
Min
120
Min
Measured at
time interval
from the start
of intrathecal
block
Mea
n ±
S.D.
Mea
n ±
S.D.
Mea
n ±
S.D.
Mea
n ±
S.D.
Mean
±
S.D.
Mea
n ±
S.D.
Mea
n ±
S.D.
Clon
idine
grou
p
82.8
±
12.4
4
76.1
5 ±
12.1
3**
75.8
5 ±
15.9
3
72.6
±
12.4
8
74.32
±12.7
6
75.1
8 ±
12.1
8
71.8
±
5.31
Heart
Rate
per
min.
Cont
rol
grou
p
86.5
5 ±
10.0
1*
82.8
5 ±
15.9
3*
76.6
±
13.1
9*
71.4
5 ±
12.3
6**
78.17
***
±
12.94
77.0
5 ±
8.92
**
78 ±
6.78
***
Clon
idine
grou
p
122.
65 ±
13.7
109.
5 ±
13.5
1
106.
95 ±
13.4
6
100.
35 ±
13.2
100.6
3
±13.8
3
107
.82
±
12.1
6
101.
94
±14.
00
Sys.
Blood
Pres.
mm
of Hg
Cont
rol
grou
p
117.
9
±
16.3
9*
105.
65 ±
13.4
1*
105.
05 ±
14.2
0*
107
±
14.0
3*
109.7
8
±
12.94
***
115.
87 ±
10.9
9*
115.
5
±
18.2
8*
Clon
idine
grou
p
73.2
5 ±
8.6
65.2
8 ±
7.99
64.5
5 ±
12.3
3
61.3
±
11.7
63.12
±13.0
2
65.8
8 ±
12.4
4
58.4
±
7.7
Diast.
Blood
Pres.
mm
of Hg
Cont
rol
grou
p
70.0
5
±
14.8
*
60.9
5
±
11.1
4*
62.5
±
12.4
2*
65.1
±
9.46*
67.33
±
7.45*
71.4
7 ±
9.07
*
72.5
±
9.57
*
* p-value > 0.05 ** p-value
significant at 0.05; *** p-value significant at
0.01
Table IV shows the incidence of complications in
both groups which were not serious enough to
warrant any intervention. There was no morbidity.
19
Table IV: Complications
Complications
Clonidine Group
(n = 20)
Control Group
(n = 20)
Bradycardia
#
5 (25%)
3 (15%)
Hypotension 4 (20%) 2 (10%)
Urinary Retention 2 (10%) 0 (0%)
Position-dependent
headache
0 0
# data are number of cases and percentage of
total.
There was no significant difference between the
groups. (p-value > 0.05)
Patients from clonidine group were found to be
more sedated but respiratory depression was not
observed.
Respiratory rate and oxygen saturation(SpO
2
)
were similar in both groups.
Discussion
Clonidine is now an acceptable adjuvant to local
anaesthetics for epidural route
1
; nevertheless
clinical trials provide evidence that less clonidine
is needed intrathecally than epidurally to produce
the same analgesic effect with fewer side effects
2
.
Hypotension was less pronounced after intrathecal
than oral clonidine
3
. Intrathecal clonidine has been
used to enhance postoperative analgesia in
cesarean deliveries, repair of femoral fractures,
and ambulatory knee arthroscopy
2-6
. According to
Niemi L
7
marked haemodynamic changes and
sedation, limits the usefulness of intrathecal
clonidine. He used very high doses (3µg/kg) of
clonidine. van Tuijl I et al
8
used very low doses of
intrathecal Clonidine (15 µg) with satisfactory
outcome. Their patients were for inguinal
herniorrhaphy and knee arthroscopy. We included
lower abdominal surgeries in our study and so we
decided to use low dose(1µg /kg) similar to
Kaabachi O et al
9
. Time required for onset of
sensory and motor blockade and peak motor
blockade was found to be similar in both groups in
our study. Though peak sensory blockade was
found to be delayed in clonidine group it has very
little clinical significance. Similar to many other
studies
9, 10
We also found that addition of 1 µg/kg
of clonidine to 0.5% bupivacaine significantly
prolongs the block (average two level regression
time, clonidine : control =129.55 : 74.5 min ) and
postoperative analgesia (8 to 10 hrs) and thus
reduces the postoperative analgesic requirement.
De Negri P et al
11
observed minimal influence on
haemodynamic parameters with 105 micrograms
of intrathecal Clonidine. We also found both
groups comparable with regard to systolic and
diastolic blood pressure at almost all time
intervals. Though heart rates started dropping in
Clonidine group after 15 minutes, maximum being
after 45 minutes, bradycardia was never severe to
be a cause for concern. In conclusion, the present
study indicates that adding clonidine 1 µg/kg to
intrathecal bupivacaine prolongs spinal
anaesthesia and the duration of analgesia. It is safe
and is as effective as bupivacaine in higher dosage
without severe adverse effects.
References
1. Persec, J., Z. Persec, and I. Husedzinovic,
Postoperative pain and systemic inflammatory
stress response after preoperative analgesia with
clonidine or levobupivacaine: a randomized
controlled trial. Wien Klin Wochenschr, 2009.
121(17-18):558-63.
2. Filos KS, G.L., Patroni O, Polyzou V., Intrathecal
clonidine as a sole analgesic for pain relief after
cesarean section. Anesthesiology. 1992 ;77(2):267-
74.
3. Dobrydnjov I, A.K., Samarütel J, Holmström B.,
Postoperative pain relief following intrathecal
bupivacaine combined with intrathecal or oral
clonidine. Acta Anaesthesiol Scand. 2002
;46(7):806-14.
4. De Kock, M., et al., Intrathecal ropivacaine and
clonidine for ambulatory knee arthroscopy: a dose-
response study. Anesthesiology, 2001. 94(4):574-8.
5. Elia N, C.X., Mazza C, Schiffer E, Tramèr MR.,
Clonidine as an adjuvant to intrathecal local
anesthetics for surgery: systematic review of
randomized trials.
Reg Anesth Pain Med. 2008;33(2):159-67.
6. van Tuijl I, van der Werff DB, Kalkman CJ., The
effect of addition of intrathecal clonidine to
hyperbaric bupivacaine on postoperative pain and
morphine requirements after Caesarean section: a
randomized controlled trial. Br J Anaesth. 2006;
97(3):365-70.
7. Niemi L, Effects of intrathecal clonidine on
duration of bupivacaine spinal anaesthesia,
haemodynamics, and postoperative analgesia in
patients undergoing knee arthroscopy.
Acta Anaesthesiol Scand. 1994 ;38(7):724-8.
8. van Tuijl, I., et al., Intrathecal low-dose hyperbaric
bupivacaine-clonidine combination in outpatient
knee arthroscopy: a randomized controlled trial.
Acta Anaesthesiol Scand, 2008. 52(3):343-9.
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9. Kaabachi O, Z.A., Ouezini R, Abdelaziz AB,
Chattaoui O, Kokki H., Clonidine
1 microg/kg is a safe and effective adjuvant to
plain bupivacaine in spinal anaesthesia in
adolescents. Anesth Analg. 2007;105(2):516-9.
10. Santiveri, X.A., A.; Plaja, I.; Metje, M. T.;
Martínez, B.; Villalonga, A.; López, M.,
Anaesthetic and postoperative analgesic effects of
spinal clonidine as an additive to prilocaine in the
transurethral resection of urinary bladder tumours.
European Journal of Anaesthesiology: 2002 ;19:
589-593.
11. De Negri P, B.F., Salvatore R, Visconti C, De Vivo
P, Mastronardi P, Spinal anaesthesia with clonidine
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... 3 Clonidine, an α2-receptor agonist, prolongs the action of LA while avoiding opioid-related side effects. [4][5][6] Many studies have compared the two drugs, but with varying results, especially concerning the duration of sensory and motor block. Our study aimed to compare clonidine and fentanyl as an adjuvant to isobaric ropivacaine for the duration of analgesia, sensory and motor block characteristics, haemodynamic stability, sedation score and any adverse event in the intraoperative and 12-hour postoperative period, in patients undergoing vaginal hysterectomy under SAB. ...
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... Intrathecal clonidine has been shown to potentiate the effect of subarachnoid block and to reduce the requirement of local anesthetic agent 10 . Intrathecal clonidine prolongs the postoperative analgesia, [3][4][5]11,12 and reduces shivering associated with subarachnoid block. Also, it is not associated with side effects seen with the use of intrathecal opioids. ...
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Background and Objective: Fentanyl and clonidine as adjuvants are commonly mixed with 0.5% bupivacaine heavy, by intrathecal route, for prolonging both sensory and motor blockade as well as for enhancing postoperative analgesia in patients undergoing major abdominal or lower limb surgery. This study was undertaken to compare the intraoperative effects and postoperative analgesia of fentanyl and clonidine, used as adjuvant to intrathecal bupivacaine during knee arthroplasty. Methodology: This prospective, randomized study was conducted on 60 patients of ASA grade I or II, between 20 and 50 years of age divided into two groups of 30 each. The patients were given 3 ml of 0.5% hyperbaric bupivacaine with either 25 mcg of fentanyl (Group F) or 50 mcg of clonidine (Group C) intrathecally. The onset of sensory and motor block, the duration of blockade, hemodynamic parameters, sedation score, total postoperative analgesia time, and side effects if any were recorded. Results: Both the groups were statistically comparable for demographic data, onset of sensory and motor blockade, duration of blockade and hemodynamic parameters. However, the sedation score was more in clonidine group. The duration of analgesia was significantly prolonged in clonidine group when compared with fentanyl group. Conclusion: In comparison to fentanyl, addition of clonidine to intrathecal bupivacaine prolongs the duration of postoperative analgesia and cause a higher sedation score. Key words: Bupivacaine, clonidine, fentanyl
... Time required for onset of sensory and motor blockade was found to be similar in both groups in our study. Similar to many other studies [6,17,18,19] we also found that addition of 75 μg of clonidine to 0.5% bupivacaine significantly prolongs the block and postoperative analgesia (8 to 10 hrs) and thus reduces the postoperative analgesic requirement. De Negri P et al [20] observed minimal influence on haemodynamic parameters even with 105 micrograms of intrathecal clonidine as reflected in our study. ...
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Background: A randomized controlled study was designed to investigate the effects of addition of clonidine to hyperbaric bupivacaine 0.5% for spinal anaesthesia in patients undergoing lower limb orthopaedic surgeries, in terms of vital parameters, onset and duration of sensory and motor block, intra and post operative pain and adverse effects. Methods: Sixty adult ASA Grade I and II patients of either sex posted for lower limb orthopedic surgeries were randomly divided equally in to clonidine or control group. Control group received intrathecal 3.0 ml of 0.5% hyperbaric bupivacaine with 0.5 ml of normal saline and Clonidine group received identical volume of intrathecal clonidine with hyperbaric bupivacaine. Results: Mean time for post operative analgesia was significantly longer in clonidine group (9.6 hours) than in the control group (3.55 hours). (p-value<0.01). Heart rate and blood pressure compared at 30 minute and 45 minute intervals were significantly less in clonidine group. ( p-value < 0.05). Bradycardia and hypotension did not require any therapeutic intervention. Clonidine group patients were found to be more sedated than control group. Conclusion: Adding clonidine 75 μg to intrathecal bupivacaine prolongs the duration of spinal anaesthesia and analgesia. It is safe and is likely to be as effective as higher doses of bupivacaine without severe adverse effects.
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Background: Anesthesiologists are responsible for the development of pain services in the current era. Hence ideal adjuvants that can be used with bupi- vacaine for stable intraoperative conditions and prolonging the postoperative analgesia with fewer side effects are being investigated. Opioids, despite use- ful as adjuvants, are associated with undesirable side effects. Aim of the work: The study was done to compare analgesic efficacy and hemodynamic of intrathecal injection of bupivacaine alone or with fentanyl, clonidine, and neostigmine in lower abdominal surgeries, over the first 24 postoperative hours, in a randomized, double-blind, and clinical trial. Methods: 100 Pa- tients were randomized into four equal groups, 25 patients in each group; Group B patients received 2.5 ml of 0.5% hyperbaric bupivacaine and 0.5 ml of normal saline. Group BF patients received 2.5 ml of 0.5% hyperbaric bupi- vacaine with (25 mics) of fentanyl. Group BC patients received 2.5 ml of 0.5% hyperbaric bupivacaine with 0.5 ml (75 mics) of clonidine. Group BN patients received 2.5 ml of 0.5% hyperbaric bupivacaine with 0.1 ml of neostigmine (50 mics) and 0.4 ml of normal saline. Intrathecal anesthesia was done with a recording of parameters intraoperative and the post-operative period. Each patient was assessed for hemodynamic parameters and effective analgesia in operation, and presence of complications (nausea, vomiting, sedation and pruritus) visual analogue pain score (VAS) postoperatively by a blinded in- vestigator in the post-anesthesia care unit (PACU) and at 1, 2, 3, 4, 8 12, 18 and 24 h postoperatively. Results: The postoperative analgesia is more effec- tive with group BC (the gold standard) than group B, group BF, and group BN. As regard complications during the study in all groups, complications as nausea, and vomiting were mainly with group BN; hypotension was primarily in group BC. Conclusion: Bupivacaine clonidine, bupivacaine neostigmine, and bupivacaine fentanyl intrathecal anesthesia produced a longer duration of postoperative analgesia after lower abdominal surgery in patients than bu- pivacaine alone. Bupivacaine clonidine mixture had the most extended period of analgesia, but with hypotension. So bupivacaine fentanyl mixture with moderate duration of analgesia and minimal side effects is most safe for a pa- tient.
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Clonidine, an alpha–2–adrenergic agonist, may have a clinically relevant analgesic action but also a hypotensive action, when administered spinally. In this study, therefore, the analgesic and circulatory effects of intrathecal clonidine were studied in patients undergoing knee arthroscopy under spinal anaesthesia. Forty ASA I–II patients were randomly divided to two groups. One group received clonidine 3 μg–kg-1 mixed with 15 mg 0.5% bupivacaine and the other group an identical saline volume mixed with bupivacaine as above, in a double–blind fashion. Sensory analgesia, blood pressure, heart rate and sedation were followed during and after the operation. Oxycodone 0.14 mg– kg“‘ i.m. or ketoprofen 100 mg p.o. was administered when needed. The duration of sensory analgesia (until regression of the block to L2) was longer in the clonidine group (mean 217 min) than in the control group (mean 160 min) (P < 0.05). Duration of motor blockade was also longer in the clonidine group (mean 215 min) compared to the control group (161 min) (P < 0.05). Mean arterial pressure and heart rate were significantly lower in the clonidine group compared to the control group. The clonidine patients needed fewer supplemental doses of oxycodone (8 doses) than those in the control group (16 doses) (P < 0.05). More patients in the clonidine group were sedated 3–6 h after the injection (P < 0.05). Addition of clonidine prolonged the bupivacaine spinal block. However, marked haemodynamic changes and sedation may limit the usefulness of intrathecal clonidine.
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With adequate control of perioperative pain it is possible to control central and peripheral inflammatory responses to surgery and influence patient outcomes. Use of analgesics before the pain stimulus (preventive analgesia) obstructs development of neuroplastic changes in the central nervous system and reduces pain. Our investigation hypothesis is that preoperative central (epidural or intrathecal) clonidine will reduce postoperative pain and the systemic inflammatory stress response more effectively than levobupivacaine. Randomized controlled study. Forty-two patients undergoing colorectal resection surgery were allocated into three groups receiving a preoperative epidural dose of (i) clonidine 5 microg/kg (n = 17), (ii) levobupivacaine 2.5 mg/ml (n = 12) or (iii) saline as a control group (n = 13). Procalcitonin, interleukin-6 and pain levels were assessed before operation, 1 h after starting, and then at 1, 6, 12 and 24 h after operation. There were no significant differences between the groups of patients in age, sex, body-mass index, body surface area and operation time. We demonstrated significant reduction (P < 0.05) in levels of procalcitonin and interleukin-6 in the preoperative clonidine group compared with the preoperative levobupivacaine and control groups. Postoperative pain levels at rest and on movement were significantly lower (P < 0.05) in the clonidine group, especially 1 h after surgery (VAS 0.82 and 1.18), than in the levobupivacaine group (VAS 5.25 and 6.67) and the control group (VAS 7.08 and 8.31). These results support the importance of the central effect of clonidine on pain pathways and blockade of the systemic inflammatory stress response.
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In a small number of studies and isolated case reports, intrathecally administered clonidine has been reported to relieve intractable cancer pain and to prolong spinal anesthesia induced by various local anesthetics. A double-blind placebo-controlled clinical trial was carried out in order to evaluate the effect of intrathecal clonidine on pain following cesarean section. Twenty patients who underwent elective cesarean section received, 45 min after general anesthesia, either 150 micrograms (n = 10) clonidine or saline (control group, n = 10) intrathecally. Pain scores were lower in clonidine- than saline-treated patients from 20 to 120 min after intrathecal injection, as measured by a visual pain linear analog scale (P less than 0.05). Pain relief, in terms of the first supplemental analgesic request by patients, lasted 414 +/- 128 min after intrathecal clonidine and 181 +/- 169 min (mean +/- SD) (P less than 0.01) after saline. Clonidine decreased systolic, diastolic, and mean arterial pressures compared to baseline values (P less than 0.05), but heart rate and central venous pressure were unaffected (difference not significant). Maximal reduction of systolic arterial pressure was 15 +/- 9%, of diastolic arterial pressure 22 +/- 12%, and of mean arterial pressure 18 +/- 12%. Clonidine did not affect arterial hemoglobin oxygen saturation or PaCO2. Patients in the clonidine group were significantly more sedated (P less than 0.05) and more frequently reported a dry mouth (P less than 0.01) compared to the normal saline group.(ABSTRACT TRUNCATED AT 250 WORDS)
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Clonidine, an alpha 2 agonist, is known to prolong the action of local anesthetics, and to provide a satisfactory analgesia; hypotension and bradycardia have been observed after its intrathecal administration. The aim of our study was to determine whether intrathecal administration of clonidine can reduce the dose of local anesthetic, and the effects of clonidine on the cardiovascular system, and on arousal level. In a prospective, randomized study we evaluated 56 patients scheduled for minor surgical procedure (spermatic vein ligature) under unilateral spinal anesthesia with hyperbaric bupivacaine 1%. One half of patients received clonidine (105 micrograms) in addition to bupivacaine. Mean arterial pressure, heart rate were recorded baseline until 1 hour after surgery. Cardiac output, stroke volume, ejection fraction, systemic vascular resistance and left cardiac work were measured, by thoracic electric bioimpedance method, baseline until 1 hour after surgery. Sensory block, motor block and sedation level were measured at the beginning of anesthesia and for 6 hours after the end of surgery. In the clonidine treated group we did not observe variations of cardiovascular parameters; in the same group we did observe sensory block and motor block significantly prolonged, a higher sedation level and a significant postoperative analgesia. In summary, the addition of clonidine to hyperbaric bupivacaine seems to be particularly useful in unilateral spinal anesthesia, exerting minimal influence on haemodynamic parameters, and guaranting a satisfactory postoperative analgesia.
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The purpose of the present study was to evaluate the postoperative analgesic and adverse effects of equal doses of oral or intrathecal clonidine in spinal anaesthesia with bupivacaine plain. Forty-five ASA I-III orthopaedic patients scheduled for osteosynthesis of a traumatic femur fracture were randomised in a double-blind fashion to one of 3 groups. Patients received 15 mg of plain bupivacaine intrathecally (group B) or an intrathecal mixture of bupivacaine 15 mg and clonidine 150 mg (group CIT). In group CPO oral clonidine 150 mg was administered 60 min before intrathecal injection of bupivacaine 15 mg. Oral and intrathecal clonidine prolonged the time until the first request for analgesics, 313 +/- 29 and 337 +/- 29 min, respectively, vs. 236 +/- 27 min in group B (P < 0.01). The total 24- h PCA morphine dose was significantly lower in group CIT(19.3 +/- 1.3 mg) compared to groups B and CPO(33.4 +/- 2.0 and 31.2 +/- 3.1 mg). MAP was decreased significantly during the first hour after intrathecal clonidine(14%) and during the first 5 h after oral clonidine(14-19%). HR decreased in CIT during the 5th and 6th postoperative hours(7-9%) and during the first 2 h(9%) in CPO (P < 0.01). The degree of sedation was more pronounced in group CPO during the first 3 h. Four patients had pruritus in group B. Addition of intrathecal clonidine prolonged analgesia and decreased morphine consumption postoperatively more than oral clonidine. Hypotension was more pronounced after oral than after intrathecal clonidine. Intrathecal clonidine is therefore recommended.
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The alpha 2-adrenoceptor agonist clonidine has potent central antinociceptive properties. The study was designed to investigate the effects of the combined subarachnoid administration of clonidine and prilocaine on spinal block and postoperative analgesia for the transurethral resection of tumours in the urinary bladder. The controlled, prospective, double-blind study enrolled 40 patients scheduled for elective transurethral resection of bladder tumours under spinal anaesthesia with prilocaine. Patients were randomly assigned to receive an intrathecal injection of prilocaine 75 mg alone (control group) or in combination with clonidine 75 micrograms. We assessed haemodynamic changes (non-invasive arterial pressure, heart rate), pulse oximetry, the upper level of block, the onset and duration of sensory and motor block, postoperative analgesia and any adverse effects. There were no statistically significant differences in demographic data, heart rate, onset time or the levels of sensory or motor block. Analgesia lasted significantly longer in the clonidine group (498.4 +/- 226.9 versus 187.2 +/- 103.1 min; P < 0.05). The duration of motor block was longer in the clonidine group (165.5 +/- 30.6 min) than in the control group (139.7 +/- 40.4 min; P < 0.05) and the duration of sensory block was also longer in the clonidine group (157.3 +/- 24.5 min) than in the control group (137.2 +/- 31.2 min; P < 0.05). Fewer patients in the recovery room needed metamizol (dipyrone) in the clonidine group (5%) than in the control group (50%). Arterial pressure decreased significantly in the clonidine group 75-135 min after the block. The addition of clonidine 75 micrograms to prilocaine 75 mg for subarachnoid anaesthesia increased the duration of sensory and motor block and reduced the need for additional postoperative analgesics by providing excellent analgesia for about 8 h during recovery from transurethral resection of bladder tumours.
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Spinal anesthesia is increasingly used in adolescents. However, the anesthesia provided by bupivacaine alone may be too short for the planned surgery. The addition of clonidine 2 microg/kg to bupivacaine provides a prolonged anesthetic action but may be associated with hypotension. In the present study, we investigated the efficacy and safety of intrathecal clonidine 1 mug/kg in adjunction to bupivacaine in spinal anesthesia in adolescents. Eighty-three adolescents, 51 males, aged 10-15 yr, scheduled for orthopedic surgery were enrolled in this placebo-controlled, randomized study. Patients were given spinal anesthesia either with plain 0.5% isobaric bupivacaine 0.2-0.4 mg/kg or bupivacaine with clonidine 1 microg/kg. The duration of sensory block was the primary outcome measure. Clonidine prolonged the duration of both the sensory and motor block. The time to regression of sensory block by two dermatomes was 136 (mean) (sd, 56) min in the adolescents with clonidine versus 107 min (sd, 42) in the controls (95% CI for diff: 5-53 min, P = 0.02). The time to full recovery of motor block was 251 min (sd, 79) in the adolescents with clonidine versus 181 min (sd, 59) in the controls (95% CI: 39-103 min, P = 0.001). Time to the first dose of rescue analgesia was longer in the adolescents with clonidine, 461 min (sd, 147) versus 330 min (sd, 138) in the controls (95% CI: 53-207 min, P = 0.01). There was no difference in the frequency of hypotension or bradycardia between the groups. In adolescents, clonidine 1 microg/kg prolonged the duration of sensory block achieved with bupivacaine by 30 min and postoperative analgesia by 120 min without severe adverse events.