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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