comparison of butarphanol and clonidine as an adjuvant to ... · lactate was started by using...
TRANSCRIPT
Abstract
Both, opioids including butarphanol and alpha-2 blockers are known to prolong
neuraxial blockade. We compared duration of analgesia and side effects of
butorphanol and clonidine in caudal block along with general anaesthesia in this
double blind, randomised, controlled prospective study. 60 ASA grade I children of
20 to 10 yrs posted for infraumbilical abdominal or genitor- urinary surgeries were
randomly divided in three groups to receive bupivacaine 0.25% 1 ml/kg with either
normal saline 1 ml (group B, control) or with butarphanol 25 mcg/ kg (group BB) or
clonidine 1 mcg/ kg (group BC) in 1 ml by caudal route. Intraoperative and
postoperative haemodynamic and respiratory parameters were recorded. Quality of
analgesia was assessed using modified objective pain score. Results were analysed
using Student's t- test and chi- square test. Both BB and BC group showed better
haemodynamic profile than group B. bradycardia and hypotension were at minimum
at this dose of clonidine. Clonidine group had duration of analgesia (460.6 ± 45.86
mins) significantly longer than BB (378.8 ± 13.31 mins) and B group but also had
higher sedation score in immediate postoperative period and can be a good option in
paediatric neuraxial blockade.
Comparison of Butarphanol and Clonidine as an Adjuvant to Bupivacaine in Caudal Anaesthesia
Introduction
ain is one of the most distressing and Pcommon effect of the disease.
Anaesthetist regards pain relief as one of
their main duty and therefore if the pain is
agony, relieving pain is ecstasy. In
children pain can induce not only acute
physical or physiological changes but also
psychological and long lasting behavioural
changes. Therefore analgesia has special
considerations in paediartic patients.
Caudal anaesthesia is a beautiful
technique used by anaesthetist for
abdominal and pelvic surgeries in
paediatric cases. Since long time opioids
Kundan Gosavi*, Nilam Virkar**, Aniruddha Nirkhi*, Deepali Dahale**,
Usha Badole***, B. D. Kondwilkar****
are being used to prolong central neuraxial
blockade. Butarphanol, mixed agonist at
kappa receptor has analgesia action
similar to that of morphine with less of
respiratory depression, less nausea,
v o m i t i n g a n d n o u n d e s i r a b l e
psychomimetic effect. Clonidine, a
versatile alpha-2 agonist is also known to
prolong central neuraxial blockade but
has slight sedative properties.
We decided to compare prolongation of
neuraxial by butarphanol and clonidine
when used as adjuvant to bupivacaine in
caudal anaesthesia.
Aim of the study
We studied 90 patients in age group
between 20 and 10 years posted for infra
*Lecturer, **Sr. Resident, ***Associate Professor, **** Professor and Head, Department of Anaesthesia, Grant Medical College, Mumbai.
Bombay Hospital Journal, Vol. 53, No. 3, 2011610
umbilical surgeries in which caudal
anaesthesia was planned.
We compared,
lEfficiency of butarphanol and
clonidine in intraoperative pain relief
and haemodynamic stability, when
given caudal epidurally in paediatric
infraumbilical surgeries.
lDuration of analgesia when combined
with bupivacaine.
lSide effects of these two combinations.
Methods of Study
After obtaining the local ethics
committee approval, 90 patients ASA 1-2,
between the ages 2-10 years posted for
infraumbilical surgeries viz: hernia repair,
orchidopexy, low anorectal malformation,
colostomy and ileostomy closure,
cystolithotomy, urethroplasty were
randomly divided into two groups.
Standard general anaesthesia along with
caudal block was planned for each case.
Valid, informed and written consent was
obtained from all the patients.
Standard intraopertive monitors were
applied: ECG, NIBP, pulseoximeter. After
cannulation of vein one pint Ringer
Lactate was started by using Holiday Segar
formula. Inj. Glycopyrrolate 0.04 mg/ kg
was given. Anaesthesia was induced with
inj. Thiopentone 5 mg/kg and tracheal
intubation was facilitated with inj.
atracurium 0.5 mg/kg. Anaesthesia was
maintained with 1mac isoflurane, 70%
nitrous oxide in oxygen.
Patients were distributed randomly in
one of two groups using the table of
random numbers.
GROUP B: received 1 ml of 0.25%
bupivacaine + 1 ml normal saline.
GROUP BB: received 1 ml/kg mixture of
0 . 2 5 % b u p i v a c a i n e a n d 2 5
micrograms/kg of butarphanol in caudal
epidural anaesthesia.
GROUP BC: received 1 ml/kg 0.25%
bupivacaine + 1 µg/ kg of clonidine HCl in
caudal epidural anaesthesia.
Intra operative data was recorded at
every 15 min interval up to extubation. No
other perioperative analgesia was given.
Anaesthesia was discontinued when the
dress ing was appl ied . Res idual
neuromuscular block was antagonized
with 0.05 mg/kg of neostigmine and 0.008
mg/kg of glycopyrrolate. After extubation,
patients were shifted to recovery room.
In recovery area, heart rate, arterial
blood pressure, respiratory rate,
saturation on air, sedation score and pain
score were recorded before shifting to
recovery room.
On arrival in the surgical ward a
dedicated nurse performed hourly
observation till the 12 hours after the
caudal block. A modified objective pain
score, given maximum score of 10 was
used to assess the pain. Supplementary
analgesia was given if the score was more
that four, in the form of i.v. paracetamol 20
mg/kg.
Respiratory rate and four point
sedation score (0 = eyes opening
spontaneously, 1 = eye opening on
speech/calling by name, 2 = eye opening
when shaken, 3 = unarousable) were also
measured every hour. Postoperative
complication and adverse effect like
episodes of nausea, vomiting, facial
flushing, sweating, pruritus, urinary
retention and psychomimetic behaviour
were noted if they occur.
611Bombay Hospital Journal, Vol. 53, No. 3, 2011
Fig. 1 Demographic Data
Mea
n V
alu
e
14
12
10
8
6
4
2
0
3.81
12.73 13.03 12.9
3.93 3.9
B (N=30) BB (N=30) BC (N=30)
GROUP
AGE yrs WEIGHT
HR/min
130
120
110
100
90
80
70
60
PRE OP 30 MIN 1 HR 2 HR 60 MIN 120 MIN 2 HR30 MIN1 HR
TIME INTERVAL
B
BB
BC
CHANGES IN HEART RATEThe data was analysed using Chi-
square test or Student - 't' to obtain the
results.
Results
Demographic data: Ninety patients were
enrolled and studied after dividing into
three groups. There were no significant
differences between three groups
regarding age (B: mean 3.81 yrs ± 2.85,
BB: mean 3.93 ± 2.67 and BC: mean 3.90 ±
2.34 yrs), weight (B mean 12.73 ± 3.96 kg,
BB: 13.03 ± 3.55 and BC mean 12.90 ±
3.56 kg p=0.759) and sex distribution.
(See fig.1 depicting of cases in two groups.)
Mean duration of surgery in group B was
(mean 78.60 ± 26.981 min), group BB
(77.12 ± 30.890) min and in group BC
(80.10 ± 12.23 min). (Statistically not
significant. P = 0.842).
Intraoperative haemodynamic status: (fig
2)
There were no significant differences
in preoperative vital parameters in two
groups.
Viz; Pulse rate: (group BB 109 ±
18.59/min, group BC111.5 ± 24.66/min),
Systolic blood pressure (SBP): (98.13 ±
13.74 mm of Hg in group BC 98.07 ± 10.38
mm of Hg).
Fig.2 Change in heart rate
The heart rate remained stable
throughout intraoperative and recovery
period in groups B and BB while in group
BC it dropped from the baseline 30 to 45
mins after caudal block to (mean 88.2 ±
12.25); p< 0.05 and remained near this
level throughout the surgery. One patient
in clonidine group had bradycardia and
needed atropine. There was slight increase
in pulse in the recovery room (p = 0.431) in
group B which became significant (106.8 ±
14.77) in postoperative period and
persisted thereafter. In butarphanol and
clonidine group pulse remained stable
throughout postoperative period.
Trends in systolic blood pressure (SBP):
(fig.3):
Fig.3. changes in systolic blood pressure.
SBP followed same trend as that of
heart rate. It remained stable throughout
the intraoperative period in all three
groups but demonstrated a significant rise
in 3 hours after surgey in B group (mean
114.6 ± 14.72) which was significant
compared to group BB and BC(P = 0.018).
13012011010090807060
Trends in systolic BP
PRE O
P
INTR
AOP
15 M
INS
30 M
IN
45 M
IN1
HR
1 HR 1
5 M
IN
1 HR 3
0 M
IN
1 HR 4
5 M
IN2
HR
RECOVE
RY
30 M
IN
30 M
IN
90 M
IN
120
MIN
POST
OP
1 HR
2 HR
3 HR
BP in
mm
Hg
B
BB
BC
Bombay Hospital Journal, Vol. 53, No. 3, 2011612
CHANGES IN RESPIRATORY RATE
35
30
25
20
15
10
PR
/ M
IN
B
BB
BC
PRE O
P
RECOVE
RY
30 M
IN
60 M
IN
90 M
IN
120
MIN
POST
OP
1 HR
2 HR
3 HR
TIME INTERVAL
This increase persisted throughout postop
period.
Changes in oxygen saturation (SpO2) and
respiratory rate: (fig.4)
There was no significant difference in
SpO2 throughout the intraoperative or
postoperative period and remained near
normal in B and BC group.
Fig.4 Changes in respiratory rate.
Respiratory rate remained on lower
side in recovery period in clonidine group
(18.45 ± 0.4), (18.16 ± 1.20), (20.89 ± 0.65)
per min; p < 0.005 but it recovered before
discharge. Only one patient in clonidine
group had apnoea in recovery room.
Though R/R was high in plain bupivacaine
group in postoperative period, it was not
significant.
Trends in pain score: (fig.5)
Fig.5 Trends in pain score
As seen here mean pain score in the
group B was less than 2 in recovery period
but had a s igni f icant value in
postoperative time. (4.12 ± 0.036), (4.12 ± st nd0.45) and (4.24 ± 0.55) during 1 , 2 and
rd3 hour respectively. Thus almost all
patients needed analgesia in postoperative
period. It was almost nil in recovery in
recovery in group BB and BC, but showed
a gradual increase in BB: (1.34 ± 0.18), st nd(2.56 ± 0.2), (4.12 ± 0.75) during 1 , 2 and
rd3 hour respectively, thus becoming
significant at the time of discharge
(p<0.05). But in BC group the pain score
remained at very low level as (0.4 ± 0.04), st nd(1.2 ± 0.30) and (1.45 ± 0.6) during 1 , 2
rdand 3 hour respectively. The rise in pain
score shown by group B and BB was
significant compared to group BC (p <
0.05).
Fig.6: mean duration of analgesia
Also mean duration of analgesia (fig.6)
as calculated from time of administration
of caudal block to that of rescue analgesia
was longer in clonidine group (460.6 ±
45.86 mins) compared to butarphanol
group (378.8 ± 13.31 mins) (P=0.00) and
plain bupivacaine group(275.8 ± 13.31
613Bombay Hospital Journal, Vol. 53, No. 3, 2011
mins); p < 0.05.
On the other hand, clonidine group
had higher sedation score (1.6 ± 0.15 at 1
hr in recovery) than butarphanol group
(0.96 ± 0.15 at 1 hr in recovery) and plain
bupivacaine group (0.96 ± 0.30). It
remained higher in clonidine group at the
time of discharge too: (0.9 ± 0.15 in BC),
(0.24 ± 0.035 BC) (0 in B) (fig.7).
Fig.7: Comparison of sedation score
Thus all three groups had achieved
score below 1 by end of 2 hrs in
postoperative period and all patients were
'ready to shift' by 2 hrs.
While 2 patients in group BB had
pruritus none of the group BC had it (P=
0.098). Similarly, 7 patients in
butarphanol group had vomiting while
only 2 patients in clonidine group did
vomit. 2 patients in BB group had
prologned urinary retention (> 6 hrs) and 4
patients in BC group had this problem
requiring catheterisation.
Discussion
The caudal block is most accepted
method of analgesia in children
undergoing lower abdominal operations,
used for providing both surgical and
postoperative analgesia. Traditionally,
opioids are used to prolong the central
neuraxial blockade but are not devoid of
side effects. There may be nausea, 30vomiting, pruritus, constipation, urinary
7,16retention, respiratory depression which
are prominent in paediatric age group.
Analgesia due to Butarphanol is due to its
agonist action at µ1 receptor and at kappa 8,13receptor. Clonidine on other hand is
devoid of these side effects but sedation
and bradycardia. We limited the dose of
clonidine to 1 mcg/kg to minimise 12,14,15,23,26them. In our search for additives
we were impressed by a study done by Lee 18and Rubin who compared clonidine +
0 . 2 5 % b u p i v a c a i n e w i t h p l a i n
bupivacaine. There are many studies on
use of opioids in caudal block including
those on butarphanol by Camman and 6 4lofferski et al and Baily et al but studies
comparing these two categories (opioids
and alpha 2 agonists) specially in
paediatric group were lacking. So we
decided to do a prospective, randomised,
double bl ind comparative study
comparing these two groups.
There were no significant differences
in demographic profile of the three groups.
Findings in our study are consistent
with other studies demonstrating
prolongation of caudal analgesia by 5,14,19,21,23 17,24,30clonidine and butarphanol
when added to bupivacaine. Luz and 19colleagues showed that the mean
duration of analgesia achieved in children
undergoing orchidopexy, hernia repair or
circumcision was comparable whether
caudal clonidine 1 mcg or morphine 30
mcg were added to bupivacaine 0.18%, 1.5
ml: 6.3 h (s.d. 3.3) h Vs. 7.1 (s.d.3.4) h
(P=0.43) for the clonidine and morphine
groups. These findings are quite similar to
what we found in our study i.e. in clonidine
Bombay Hospital Journal, Vol. 53, No. 3, 2011614
group (460.6 ± 45.86 mins) compared to
butarphanol group (378.8 ± 13.31 mins)
(P=0.00) and plain bupivacaine group
(275.8 ± 13.31 mins); p < 0.05. Clonidine
has also shown to prolong the analgesia of
peripheral nerve block when used with 10 27ropivacaine and mepivacaine and
20,22epidural lignocaine Erne Brand and 11colleagues also showed that clonidine
enhanced the hyperpolarising and
reduced the depolarising after potential
that follow compound action potentials
during electrical activity. Intraoperative
haemodynamic stability shown by both
groups was due to intense analgesia
provided by the combinations. Increase in
heart rate and SBP in recovery shown by
BB group was due to shorter duration of
analgesia provided by butarphanol as
compared to clonidine. Indeed pain score
in BB group (4.12 ± 0.75) was higher
compared to group BC (1.45 ± 0.6) at the
time of discharge. High solubility of
butarphanol leading to its early exit from
CSF may explain its shorter duration of 2analges ia . But maintenance o f
haemodynamic stability in BC group can
be explained by two factors: first is
prolongation of analgesia by clonidine and
second is cardiovascular properties of
clonidine flow which may have worked as
privilege in our study. Epidurally
administered clonidine also decreases the
electrical activity of preganglionic
sympathetic nerves. Bradycardia is
caused by an increase in vagal tone
resulting from central stimulation of
parasympathetic outflow, as well as 1reduced sympathetic drive. The decrease
in heart rate due to clonidine is also said to
be due to inhibition of acetylcholine 3esterase. It is clear from previous studies
that clonidine has spinal as well as supra
spinal action. Though heart rate was lower
in clonidine group; only one patient
required atropine treatment.
In clonidine group apnoea was seen in
one patient, otherwise clonidine showed
no additional respiratory depression. This
can be seen by the fact that there was no
significant difference in mean oxygen
saturation and respiratory rate between
both groups.
Sedation due to clonidine is a
supraspinal phenomenon and even in
higher doses given epidurally, degree of
respiratory depression is lesser than that 9 15,25,28,29of sedation Many investigators did
not find any respiratory depression or
sedation that required treatment with 1
mcg/ kg caudal clonidine. Incidence of
vomiting and pruritus was higher in
butarphanol group, but almost all the
patients in all the 3 groups had achieved
'can be shifted to ward' status.
Conclusion
In conclusion it can be said that, when
used by caudal route clonidine in dose of 1
mcg / kg provides longer duration of
analgesia. The feared side effects of
clonidine, mainly bradycardia and
respiratory depression are at minimum at
this dose and both butarphanol and
clonidine can serve as a good tool for
anaesthesiologist in paediatric cases.
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Book Review
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