EL-MINIA MED., BULL., VOL. 18, NO. 1, JAN., 2007
Asida et al
CAUDAL ROPIVACAINE WITH AND WITHOUT NEOSTIGMINE FOR
PEADIATRIC SURGERY
By
Salah M. Asida , MD; Mamdouh A. Magid, MD; Ahmed Korany, MD.
Department of Anesthesia, El-Minia Faculty of Medicine
ABSTRACT:
This study was designed to evaluate the effect of the addition of neostigmine to
ropivacaine given via the caudal route to children undergoing lower abdominal
surgical operations for postoperative pain relief.
Methods: The study included sixty patients 1-5 years of age admitted for lower
abdominal and lower extremity operations and divided into two groups : group (R)
30 patients received 0.5 ml/kg of 0.2% ropivacaine via the caudal route , group (N) 30
patients received 0.5 ml/kg of 0.2% ropivacaine plus 2 ug /kg neostigmine via the
caudal route. pulse oximetry, heart rate and mean arterial blood pressure were
recorded before and after induction of anesthesia and every 10 minutes for one hour
or till the end of operation . Toddler-preschooler postoperative pain scale pain score
(TPPPS) table (1) was recorded after extubation and every 2 hours for 24 hours, a
pain score greater than 3/10 required the administration of rectal paracetamol or
declophenac sodium (NSAID) .
Results: patient's characteristics and hemodynamic data were comparable in both
groups, there was no significant difference between the two groups as regards the
duration of surgery and anesthesia .sedation score was significantly higher 2 hours
after extubation in group (N) .the pain score was significantly lower at 4,6,12 hours
postoperatively in group (N). The total analgesic requirements as well as the number
of patients received such analgesics post operatively was significantly lower in group
(N) also, the time to first analgesic requirement was 6 hrs in group (N) when
compared with group (R) 4 hrs (p ≤0.05). as regards the incidence of adverse events
we found no significant difference between the two groups .
Conclusion :we found that the addition of neostigmine to ropivacaine given by the
caudal route to children does improve the quality of anesthesia and postoperative
analgesia more than ropivacaine alone.
KEYWORDS:
Ropivacaine
Neostigmine
Caudal block .
is simple, safe and with high success
rate .the addition of drugs to local
anesthetic so that the duration of
analgesia becomes extended beyond
the duration of action of the injected
local anesthetic becomes increasingly
popular2. Various drugs had been tried;
adrenaline3,
clonidine,
ketamine4
5
,different opioids
with different
degrees of success in prolonging the
INTRODUCTION:
Children undergoing surgical
operations usually require general
anesthesia .the use
of the caudal
route for administering anesthetic to
these children as an adjuvant to general
anesthesia is a common procedure1 .it
may be used from the start of surgery
or by the end of operation to provide
postoperative analgesia. Caudal block
447
EL-MINIA MED., BULL., VOL. 18, NO. 1, JAN., 2007
postoperative
pain-free
duration.
Neostigmine is used commonly for
decurarization after the use of nondepolarizing muscle relaxants. It has
been tried also in the intrathecal6 and
epidural7 spaces. It acts by inhibiting
the breakdown of acetylcholine in the
spinal cord. Another suggested
mechanism of analgesia is by
increasing
cyclic
guanosine
monophosphate by generating nitric
oxide8. It has been found to enhance
the onset of action of tetracaine
analgesia9. In adult patients epidural
neostigmine with lidocaine produced
dose dependent analgesic effect and a
reduction in postoperative analgesic
consumption without increasing the
incidence of adverse events10. Studies
has been done on epidural neostigmine
added to bupivacaine for abdominal
hysterectomies with accepted results11.
The objectives of this study is to
evaluate the effect of addition of
neostigmine to ropivacaine by the
caudal route for children undergoing
lower abdominal operations
Asida et al
study. A teaspoonful of oral
midazolam was given to the patient
one hour before induction of
anesthesia. Heart rate, mean arterial
pressure, and oxygen saturation were
measured
and
recorded
before
induction of anesthesia which was
induced by face mask inhalation of
sevoflurane and sixty percent nitrous
oxide in oxygen. After loss of eye lash
reflex a 22 gauge canula was inserted
in a superficial vein for fluid and drug
administration. An endotracheal tube
was placed facilitated by atracurium
0.5 mg/kg I.V. Ventilation was
controlled and maintained manually
by an Ayre's T piece or a pediatric Y
anesthetic circuit. Patient is then placed
in the left lateral position with the hips
flexed and the knees, the upper knee
being more flexed than the lower. The
back of the patient was painted with an
antiseptic solution. The triangular area
of the sacral hiatus was identified by
palpating the two sacral cornua at the
end of the vertebral spinous process.
The needle of 5 cc. syringe (gauge 22)
is inserted perpendicular to the skin
until it pierces the sacrococcygeal
membrane noted as an increase in
resistance and a characteristic pop is
easily felt. The needle is then
redirected slightly rostrally 15-20
degrees and advanced 2-3 mm in the
sacral canal according to the child's
age and height. Aspiration for blood or
CSF is performed before injection of
either 0.5 ml/kg of 0.2 % ropivacaine
in group R, or the same dose of
ropivacaine plus 2 ug/kg neostigmine
in the group N. each group 30 patients.
The study used a double blind
methodology with random allocation to
the two groups by a computer
generated list. Study solutions were
prepared by anesthesiologist not
involved in the patient's anesthetic
procedure. Heart rate, MAP, SpO2
were recorded before induction, after
induction and then every 10 minutes
PATIENTS AND METHODS:
This study had been done in the
anesthesiology department of Elminia
university hospital in the period
between marsh 2005 and marsh 2006.
Sixty patients participated in the study.
A written informed consent was taken
from the patient's parents. The study
design was randomized and double
blind.
Patients
were
randomly
allocated according to a computer–
generated randomization. Routine
clinical examination and laboratory
investigations were done. ASA I
children aged 1-5 years undergoing for
example
inguinal
hernia
or
hypospadius (and other operations)
were included in the study, while
patients with local infection in the back
or obvious neurological disease and
those with a history of bleeding
tendency were excluded from the
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EL-MINIA MED., BULL., VOL. 18, NO. 1, JAN., 2007
after caudal block. Assessment of
adequacy of caudal block analgesia
was determined by hemodynamic
stability; an increase of heart rate and
or MAP by 15% of baseline value
indicate failure of the block provided
the sevoflurane concentration was kept
0.6 MAC. Otherwise, we give an
additional dose of fentanyl 2 ug/kg
I.V. Fluid therapy was standardized
during and after surgery in the form of
lactated ringer's solution 6ml/kg /hr
and 5% dextrose in water 4 ml/ kg /hr
in
the
postoperative
period.
Hemodynamic data were continued to
be recorded 30 min after extubation
and at 2,4,6,12and 24 hrs. On
awakening, we assessed motor block
by the modified Bromage scale
considering 0 as full motor strength
(flexion of knees and feet); 1 flexion of
knees only; 2 little movement of feet
only; 3 no movement of knees and feet.
For young children who cannot move
their legs and feet on command we
stimulated their legs and feet to assess
mobility.
A
toddler-preschool
postoperative pain scale15. ( TPPPS)
modified to give a maximum score of
10 (table 6) was used for postoperative
pain evaluation. Sedation score were
also measured postoperatively (0 =
eyes open spontaneously, 1 = eyes
open to speech, 2 = eyes open when
shaken, 3 = unarousable. Assessment
of postoperative pain and sedation
were measured 30 minutes after
extubation and at hours 2,4,6,12 and 24
hours.when we found the pain score
greater than 3/10 we administered 20
mg/kg paracetamol rectally. The
duration of postoperative analgesia was
defined as the time between caudal
drug injection and the first rectal
paracetamol administration, if no rectal
paracetamol was given within 24 hours
then the duration of analgesia was
counted as 24 hours. The total
analgesic requirements during the
study period and the amount of
Asida et al
supplementary analgesia required by
each child in 24 hours and any local or
systemic complications were recorded.
The same person performed all
measurements for all patients.
STATISTICAL ANALYSIS:
For the patient's characteristics,
type
and
duration
of
surgery,MAP,HR,SpO2, total analgesic
consumption,
first
analgesic
requirement and adverse events we
used the unpaired t test to compare the
two groups. Pain and sedation scores
were analysed by the Mann-Whitney U
test as well as the amount of
supplementary analgesia required by
each child. Paired t test was used to
compare the intraoperative and
postoperative hemodynamic data with
preoperative base line data.a p value of
less
than
0.05was
considered
statistically significant.
RESULTS:
We devided our patients
randomly into 2 groups 30 patients in
each group . there were no differences
between the two groups concerning
age, weight, height,
duration of anesthesia (table: 2).we
found no statistically significant
difference between groups as regards,
HR, and (fig.1). No changes in mean
arterial pressure was found (fig.2),
both intra and postoperatively. As
regards TPPPS there was no significant
difference between groups in the first 2
hours of the study. There was mild
significant difference at 4 hours and
highly significant difference at 6 and
12 hours postoperatively, P value
<0.001.being lower in group of
neostigmine (table: 3).There was
insignificant
difference
between
groups as regards sedation score except
at 2 hours postoperatively being lower
in group of ropivacaine (table:4). The
number of patients and the number of
doses received postoperative analgesia
449
EL-MINIA MED., BULL., VOL. 18, NO. 1, JAN., 2007
was higher in the group R (ropivacaine
alone) than the group N ( ropivacaine +
neostigmine) p valua < 0.001.the first
analgesic requirement was statistically
prolonged in group N while total
Asida et al
analgesic consumption was higher in
the group R (table:5). we found no
statistical difference between the two
groups as regards adverse events
(table:6).
Table (1): the toddler –preschooler postoperative pain scale.
Score 0
Score 1
Score 2
Verbal
complaint/
cry
none
Once only
> once
Groan/
moan/
grunt
none
Once only
> once
grimace
none
Once only
> once
Restless
motor
behavior
none
One episode
> one episode
Rub/touch
painfull area
None
Once only
> once
Table (2):Patient's characteristics (mean ± SD -range) :-
Age (years)
Weight (kg)
Height (cm)
Group R (n=30)
3.4±1.1
(2-4.5)
14.16±3.3
(10.7-17.4)
86.5± 4.9
(81.5-91)
Group N (n=30)
3.3±1.07
(2.3-4.4)
14.06±3.2
(10.8-17.6)
85.9± 5.7
(80.2-91.6)
8
10
4
3
2
3
84± 19
(104-65)
7
11
1
4
3
4
86± 17.7
(103-69)
Type of surgery
Hypospadius
Congenital hernia
Undescended testis
Stone bladder
Skin grafts
Hydrocele
Duration of anesthesia ( minutes)
R= ropivacaine
N= neostigmine
SD= standard deviation.
P value
NS
NS
NS
NS
NS= no significance
Unpaired t test was used in this table.
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EL-MINIA MED., BULL., VOL. 18, NO. 1, JAN., 2007
Asida et al
Table (3): Changes in the values of TPPPS scale in the two groups: mean± SD - range
Group R (n=30)
Group N (n=30)
P value
1.00
±
0.98
0.83
±0.87
NS
30 min
(1-2)
(1-2)
post-extubation
1.00 ± 0.98
0.93 ± 0.82
NS
2 hrs
(1-2)
(1-2)
2.00 ± 1.33
1.16 ± 1.05
*
4 hrs
(0.7-3.3)
(0.2-2.3)
2.9 ± 1.86
1.33 ± 1.34
***
6 hrs
(1-3.8)
(0.3-2.7)
2.96 ± 1.37
1.20 ± 1.18
***
12 hrs
(1.6-4.2)
(0.2-2.3)
0.56 ± 0.72
0.53 ± 0.62
NS
24 hrs
(0.5-1.3)
(0.4-1.2)
TPPPS =toddler pre- school postoperative pain score
 = mild significance p< 0.05 *** = high significance p< 0.001 NS = no significance.
 Mann-Whitney U test was used in this table.
Table (4): Changes in the sedation score in the two groups ( mean ± SD - range)
Group R (n=30)
Group N (N=30)
P value
0,86 ±0.97
1.26 ± 0.86
NS
30 min post-extubation
(0.33-1.7)
(0.5-2.2)
0.20 ± 0.04
0.53 ±0.50
**
2 hrs
(0.16-0.24)
(0.04-1.3)
0.00 ± 0.00
0.10 ± 0.30
NS
4 hrs
0.00 ±0.00
0.10 ± 0.30
NS
6 hrs
0.00 ± 0.00
0.00 ±0.00
NS
12 hrs
0.00 ±0.00
0.00 ±0.00
NS
24 hrs
** = moderate significance p< 0.01
Mann-Whitney U test was used in this table.
Table (5): Analgesic requirements in the two groups :Group R
(n=30)
22
Number of patients received analgesia
2 doses of
Total analgesic requirements
paracetamol
After 4 hrs post
time to first analgesic inquiry
op. 5 patients
The unpaired t test was used in this table.
Table (6): Comparison of adverse events in the two groups :Group R (n=30)
Group N (n=30)
Nausea
1
2
Vomiting
Excessive sedation
Urine retention
Respiratory depressionThe unpaired t test was used in this table.
451
Group N
(n=30)
6
One dose of
paracetamol
After 6 hrs post
op. 4 patients
P value
NS
NS
NS
NS
NS
P
value
***
**
**
EL-MINIA MED., BULL., VOL. 18, NO. 1, JAN., 2007
Asida et al
124
122
g
120
118
116
114
112
base
line
after 10 min 30 min 50 min 70 min 1/2 hr
induc
postex
group R
2hrs
4hrs
6hrs
12hrs
24hrs
group N
Fig. 1 changes in heart rate
After induc= after induction
postex= postextubation
group R
group N
Fig. 2 : changes in mean arterial blood pressure
452
12
hr
s
24
hr
s
rs
6h
rs
4h
rs
2h
at
ba
se
lin
e
in
du
c
10
m
in
30
m
in
50
m
in
7
1/
0
2h mi
n
r
po
st
ex
70
60
50
40
30
20
10
0
EL-MINIA MED., BULL., VOL. 18, NO. 1, JAN., 2007
Asida et al
Turan et al. similar to our study . they
tried at first neostigmine with
bupivacaine caudal and changed the
local anesthetic to ropivacaine13 . we
continued that work with ropivacaine
from the start as we believe it safer
specially for children as it has some
affinity to the sensory C fibers thus
producing less motor block . our
results were very near to those of
Turan but the duration of analgesia was
longer in our study than other studies
may be due to the difference in the way
of evaluating pain and how the child
could express feeling pain.
DISCUSSION:
This study was done to evaluate
the benefit of addition of neostigmine
to the local anesthetic ropivacaine
given by the caudal route to children
undergoing
lower
abdominal
operations the addition of neostigmine
had prolonged the period of
postoperative analgesia from 4 hours in
group R to 12 hours in group N.
(table:3) determined by the time to first
analgesic requirement. Neostigmine
when injected in the subarachnoid
space produces analgesia in animals,
volunteers, and in patients by inhibiting the breakdown of the acetylcholine . acetylcholine acts on spinal
mus-carinic receptors which are
believed to play a role in the analgesic
action of neostigmine10. It has been
found that the muscarinic binding sites
are found in the substantia gelatinosa
and to a lesser extent in the laminae III
and V in the dorsal horn of the spinal
cord coincident with opioid and
adrenergic sites12.the analgesic actions
of anticholine-sterases such as
physostigmine is thought to be due to
indirect
stimulation
of
spinal
muscarinic receptors (M I) and the
supraspinal muscarinic receptors (M I
and M2) and nicotinic cholinergic
receptors. In adults neostigmine was
added to bupivacaine given by the
epidural route and produced longer
duration
of
post
hysterectomy
analgesia11 ,this study done by
Nakayama et al. where10 ug/kg
neostigmine
combined
with
bupivacaine given by the epidural
route was more effective than
bupivacaine
alone
in
reducing
postoperative pain. Lauretti et al.
found epidural neostigmine (1, 2, 4
ug/kg with lidocaine produced a dosedependent analgesic effect and a
reduction of postoperative analgesic
consumption.
Without
increasing
10
adverse
event .
In
peadiatric
anesthesia we found a study done by
However, the results of our
study agree with other studies as
regards the duration of analgesia and
the
reduction
of
postoperative
analgesic requirements. Neostigmine
produces
unwanted
muscarinic
14
effects
such
as
arrhythmia,
bradycardia ,bronchospasm, increased
bronchial
secretions,
increased
salivation and increased incidence of
nausea and vomiting. Some of these
side effects were reported in preclinical
screening studies of intrathecal
neostigmine done long ago6. Reports
about nausea and vomiting, subjective
leg weakness, spontaneous micturition
and defecation , increased blood and
heart rate were recorded but in our
study we did not encounter such side
effects in a statistically considered
manner perhaps because of the limited
number of case included in the study
and perhaps because of the very low
dose of neostigmine used in the study.
We conclude that the addition of
neostigmine to ropivacaine given by
the caudal route dose produce
prolonged postoperative pain-free
period in children than ropivacaine
alone.
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‫‪EL-MINIA MED., BULL., VOL. 18, NO. 1, JAN., 2007‬‬
‫استخدام الروبيفاكين مع وبدون النيوستجمين أثناء‬
‫الحصار الذيلى فى جراحة األطفال‬
‫صالح مصطفى عصيدة – ممدوح عبدالمعطى ماجد – أحمد قرنى‬
‫قسم التخدير – كلية طب المنيا‬
‫أجريت هذه الدراسة بمستشفى المنيا الجامعى علىى ‪ 06‬طفى تتىرا ا ا‘مىاره مىع عىا‬
‫إلى خمسة أع ا قد أجريت له جراحات مختلفة فى الجهازيع الب لى التناسلى فىى‬
‫األطراف السفلى الهدف مع هذه الدراسة ه تقيي التأثير المسكع لألل األثار الجانبية‬
‫(إع جدت) الناتجىة عىع إعطىاق عقىار الني سىتجميع مى عقىار الر بيفىاكيع عىع طريى‬
‫الحصار الذيلى لهؤالق األطفال لذا ت تقسيمه إلى مجم عتيع للبحث‪:‬‬
‫‪ ‬المجم عة األ لى عدده (‪ )06‬ت إعطاؤه ر بيفاكيع فقط‬
‫‪ ‬المجم عة الثانية عدده (‪ )06‬ت إعطاؤه ر بيفاكيع ‪ +‬ني ستجميع‬
‫قد ت متابعة دقيقة للمرضى أثناق بعد الحقع عع طري قياس النبض ضىطط الىد نسىبة‬
‫تشىىب الىىد باألكسىىجيع كىىذلس ت ى قيىىاس مسىىت فقىىداع الحركىىة باسىىتخدا مقيىىاس بر مىىا‬
‫مقياس التأثير المهد ق مقيىاس األلى المرئىى تى حسىاس إسىته س المسىكنات أثنىاق بعىد‬
‫الجراحة كذا األثار الجانبية (إع جدت)‬
‫تحليل نتائج البحث جد إع إضىافة عقىار الني سىتجميع إلىى عقىار الر بيفىاكيع عىع طريى‬
‫الحصار الذيلى لألطفال له مميزات أكثر مع إستخدا الر بيفاكيع حىده حيىث أنىه يزيىد مىع‬
‫فترة عد اإلحساس باألل أثناق بعد العملية يقلل مع كمية إسته س المسكنات بعد الجراحة‬
‫د ع أثار جانبية تذكر لذا ننصح باستخدامهما معا فى تخدير جراحات األطفال‪.‬‬
‫‪455‬‬