Nalbuphine Bupivacaine in Subarachnoid block
ORIGINAL ARTICLE
A Comparison of Intrathecal Nalbuphine Hydrochloride with Hyperbaric
bupivacaine 0.5% and Hyperbaric bupivacaine 0.5% Alone in patients undergoing
abdominal hysterectomy
Apeksha A. Patwa1*, Archana Endigeri2, M.R. Upadhyay3
1
Assistant Professor, 2Resident, 3Professor and Head, Department of Anaesthesiology, Medical College, Vadodara
ABSTRACT
BACKGROUND: Nalbuphine is a synthetic mixed agonist antagonist opioid, which produces k receptor
mediated analgesia to control mild to moderate pain without producing µ receptor mediated side effects,
when used intrathecally with bupivacaine. Hence we carried out this randomized single blind study to
evaluate the effects of addition of 1mg of Nalbuphine to 0.5% hyperbaric bupivacaine intrathecally.
MATERIALS AND METHODS: 60 female patients belonging to ASA grade I/ II scheduled for abdominal
hysterectomy were randomly allocated into 2 groups of 30 each. GROUP B: received bupivacaine heavy
0.5% 3cc(15mg) + 0.5cc sterile water GROUP B: received bupivacaine heavy 0.5% 3cc(15mg) + 0.5cc
sterile water, GROUP BN: received bupivacaine heavy 0.5% 3cc(15mg) + 0.5cc(1mg) Nalbuphine.
intrathecally. The characteristics of sensory and motor blockade, duration of effective analgesia,
perioperative hemodynamic, respiratory parameters and complications were recorded , tabulated and
statistically analysed. RESULTS: In our study no statistically significant difference was observed in the
onset of sensory and motor block between the two groups (p>0.05). The two segment regression time
was significantly prolonged in Group BN(98.16±9.86mins) compared to Group B(77.33±9.35mins). The total
duration of effective analgesia (time from intrathecal drug injection to the point of time when VAS≥4)
was also significantly prolonged in Group BN(302.4±27.59mins) compared to Group B(180.83±25.90 mins).
The hemodynamic, respiratory parameters and intraoperative complications were comparable in both the
groups. CONCLUSION: Intrathecal Nalbuphine combined with bupivacaine prolongs the duration of
sensory blockade and postoperative analgesia.
Keywords: Nalbuphine, Bupivacaine, Subarachnoid block
INTRODUCTION
Spinal anaesthesia is one of the most commonly
used anaesthesia techniques for lower abdominal
and lower limb surgeries due to its well-known
advantages. The commonly used agents in spinal
anaesthesia are lignocaine and bupivacaine.
Lignocaine has quick onset but shorter duration of
action i.e. about 1 to 1.5 hours, Bupivacaine on the
other hand has comparatively longer duration of
action i.e 2 to 2.5 hours. Many drugs were identified
to be used as adjuvants to bupivacaine spinal
anaesthesia for prolongation of its action and post
operative analgesia as there is a complex system of
interaction of different receptors for the
transmission and inhibition of nociception in the
spinal cord. The technique of intrathecal opioid
administration along with local anesthetics has been
found to provide superior quality of analgesia after a
variety of surgical procedures1. The rationale for
*Corresponding Author
Dr. Apeksha A. Patwa,
B-31/32, Kailash Park Duplex, AIN Oxygen Line,
Akshar Chowk, Old Padra Road,
Vadodara-390020
Email:- patwaapeksha@gmail.com
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Int J Res Med. 2014; 3(2);7-11
the combination of opioids and local anesthetics is
that these two types of drugs eliminate pain by
acting at two different sites; local anesthetics act at
the nerve axon and the opioids at the receptor site in
the spinal cord. Intrathecal opioids are used widely
in treating intraoperative, postoperative, traumatic,
obstretic, chronic and cancer pain. Nalbuphine is a ĸ
receptor agonist, μ receptor antagonist opioid and its
intrathecal administration has been found to provide
good intraoperative and post operative analgesia in
various lower abdominal and lower limb surgeries
with decreased incidence of μ recptor side effects.
Thus we decided to undertake this randomised study
to evaluate the effects of intrathecal Nalbuphine
1mg added to 0.5% Hyperbaric Bupivacaine in
comparison with 0.5% Hyperbaric Bupivacaine
alone in patients undergoing abdominal hysterectomy.
MATERIALS AND METHODS
After the approval of hospital ethical committee; A
single blind randomized
clinical study was
conducted on 60 adults patients of ASA I & II,
between the age group of 30-60 years, undergoing
abdominal hysterectomy at SSG Hospital ,Govt.
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Medical college Vadodara during the period of
January 2012 to April 2013 Inclusion criteria:
ASA grade I and II, Female patients of the age
group between 30-60 yrs, Patient is able to give
written and informed consent and understand test
regarding assessment of pain. Exclusion criteria:
Any contraindication to spinal anesthesia. Those
with respiratory disorders. Prior history of opioid
and other substance abuse. History of drug allergy.
Patients unwilling to participate in study. ASA
grade III and IV. Explanation and consent. All the
selected patients were explained about the purpose,
procedure and side effects of the study. They were
also explained about assessment of pain with the
help of Visual Analogue Scale. After this a written
and informed consent was taken. Tab Ranitidine150
mg and Tab Diazepam 10 mg was given to all
patient the night before the surgery. Group of
patient : Patients were randomly assissgned in one
of the following two groups Group B : Hyperbaric
Bupivacaine 0.5% (3 ml) + 0.5 ml sterile water
Group BN: Hyperbaric Bupivacaine 0.5%( 3 ml) +
0.5 ml of Nalbuphine Total volume administered3.5ml (Preparation of the drug,1mg Nalbuphine-1
ampoule contains 10mg.1/2 ml is taken and diluted
upto 2.5ml,thus making 1mg in 0.5ml) Anaesthetic
procedure: patients were premedicated with
Inj.Atropine 0.6mg I.M Inj. Ranitidine 50mg I.V
both half an hour before surgery. Preloading was
done with Inj. Ringer Lactate 10ml/kg body weight
20 minutes before induction. Spinal anaesthesia
was given under all aseptic and antiseptic
precautions using 23 g quincke’s type spinal needle.
Patients were turned supine immediately at the end
of the injection, time of which was defined as
‘zero’. Observations were recorded as shown
below. Patient having no or inadequate surgical
anaesthesia were excluded from the study.post
operatively patient was observed for 24hr for any
complications. Observations: Sensory block was
checked by using pin prick method (sing tip of 24g
hypodermic needle)
1. Onset of sensory block: Immediately after
spinal injection patients were checked for loss
of pin prick sensation at L1 dermatome. that
time was taken as onset of sensory block.
2. Highest sensory level achieved.
3. Two segment regression time: Time interval
from highest sensory level achieved to two
segment regression of sensory block.
4. Duration of sensory block: Time interval from
onset of sensory block to regression of sensory
level to L1 dermatome again.
Motor block: motor block was noted as per bromage
scale which is as follows
grade 0 - no muscular weakness
grade I - unable to flex hip
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grade II - unable to flex knee
grade III - unable to flex ankle
Following things were observed in motor block:
1. Onset of motor block. time interval from
intrathecal injection to achievement of motor
block of bromage grade I
2. Maximum motor block achieved
3. Duration of motor block (time interval from
onset of motor block to regression of motor
block to bromage grade 0)
Vital parameters: vital parameters like pulse rate,
blood pressure, respiratory rate, oxygen saturation
were monitored. Recording was done before giving
block and then at 1,
3 and 5 mins, then at every
5 min interval upto 15 mins and then every 15 mins
till the end of surgery. Duration of surgery, total
amount of blood loss and fluid replaced were noted.
Postoperative period: Vital parameters were
recorded initially at 30 min interval for 2hrs then
every hourly till 6 hrs then every 12hrs till 24hrs.
Pain assessment: It was done every half hourly for
initial 6hr then hourly for 12hr by using visual
analogue scale (VAS).The duration of effective
analgesia was counted from onset of sensory block
to when VAS score of ≥ 4. At this time, patients
were given rescue analgesic inj. Diclofenac sodium
1.5mg/kg im. Patients were monitored for various
intra and postoperative complications.
 Bradycardia: defined as pulse rate less than
20% of preblock value. It was treated with Inj.
Atropine 0.6mg IV bolus.
 Hypotension: defined as fall in systolic blood
pressure more than 20% of pre-procedure
value. Inj. Ephedrine 5 mg IV bolus and
crystalloid fluids to be given when hypotension
occurs.
 Respiratory depression: defined as respiratory
rate less than 10/min or oxygen saturation less
than 90%. It was to be treated with oxygen if
required.
 Nausea, Vomiting, Pruritus, high spinal etc
Statistical methods: Using Medcal-C software and
taking an alpha error of 0.01 and beta error of 0.01
for the parameter Duration of effective analgesia the
minimum sample size required to conduct the study
would be 22 per group.In order to compensate for
the greater variability,30 patients were included in
each group. Statistical analysis:
 The results of the study were tabulated &
statistically compared.
 Chi square test was used for qualitative
data(ASA grade, motor grade).
For rest of the quantitative data, student t test was
used(unpaired) The p-value was considered
significant as shown below:
1). p > 0.05 not significant
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Nalbuphine Bupivacaine in Subarachnoid block
2). p < 0.05 significant
3). p < 0.001 highly significant
RESULTS
The two groups are comparable to each other with
respect to age, weight and ASA physical status. The
mean duration of surgery in both the groups showed
no significant difference. The mean onset of sensory
block was (115.66 ± 33.99 seconds) in group B
while in group BN it was (102.33 ±29.87 seconds)
Thus onset of sensory block was comparatively
earlier in group BN (p>0.05) In majority of the
patients maximum sensory level achieved was T4T6 in group B and T6-T8 in group BN. Two
segment regression time
was( 77.33 ± 9.35
minutes) in Group B as compared to (98.16 ± 9.86
minutes) in Group BN (p<0.001). Duration of
sensory block was (153.33 ± 25.33 minutes) in
Group B, whereas it was( 242.5 ± 22.46 minutes) in
Group BN. (p<0.001)
Figure 1: 2-Segment regression time (MINS)
Figure 2: Duration of sensory block
The mean onset of motor block in Group B was
(123.66 ± 30.11 seconds), while it was, (133.83 ±
24.55 seconds) in group BN (p>0.05). The
maximum motor block achieved was of grade III on
Bromage scale in all the patients of both the groups.
The duration of motor block was (192.33± 23.80
minutes) in Group B, while it was (205.33 ±16.70
minutes) in Group BN(p>0.05) Changes in mean
pulse rate on inter and intra group comparison,
showed no significant difference in intra as well as
post operative period .On comparing the mean
systolic and diastolic blood pressure after spinal
anaesthesia the intra group comparison showed
significant fall in systolic blood pressure 3 minutes
after giving the block and persisted for 30 minutes
after the instillation of drugs, there after the
difference remained insignificant throughout the
intra operative period. However this fall was well
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within 20% of preblock values and there was no
statistical difference on inter group comparison.
There was no change in the mean respiratory rate as
well as mean oxygen saturation as measured by
pulsed oximeter during intra as well as post
operative periods the( p>0.05) Respiratory
depression was not observed in any of the patients
of both groups throughout the perioperative period.
The duration of effective analgesia in group B was
(180.83±25.90minutes) and that in group BN was
(302.4 ± 27.59 minutes).The difference was
statistically highly significant (p<0.001).
Figure 3: Duration of effective analgesia (MINS)
The number of rescue analgesic needed were
(2.83±0.37) in Group B as compared to (1.9± 0.30)
in Group BN (p<0.001) during 24 hours post
operative period Nausea occurred in 2 patients of
either groups. In the Group B 5 patients had
hypotension, whereas in Group BN 2 patients had
hypotension. No other intra operative complications
were observed in both the groups. No post operative
complication were observed in any of the patient
groups.
DISCUSSION
Spinal Anaesthesia is the first choice for lower imb
and gynaecological surgeries. The surgical stress
response peaks during the postoperative period and
has major effects on almost all body systems. A pain
and stress free postoperative period brings about
early mobilization and recovery thereby reducing
the morbidity and mortality of any surgical
operation. It has been well documented that the
combination of opioid and local anaesthetics
administered intrathecally has a synergistic
analgesic effect thus providing powerful
potentiation of analgesia by local anaesthetic
Opioids however act through various receptors1,2.
Plethora of studies has shown that spinal opioids can
provide profound post operative analgesia with
fewer central and systemic adverse effects than with
opioids administered systemically3. Most commonly
used intrathecal opioids are mu agonist drugs which
provide excellent analgesia but carry along with
them various mu mediated side effects 4.Eventually
it was established that significant analgesia can be
obtained by kappa binding sites as well with the
added advantage of bypassing mu related side
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effects2,4. Nalbuphine is a mixed agonist-antagonist
drug,when it binds to μ receptor it serves only to
competitively displace other μ agonists from the
receptor without itself displaying any agonist
activity similar to those of naloxone. However,
when it binds to k receptor, it has agonist activating
effect similar to that of endogeneous dynorphins4.
A randomized, study was carried out to compare
the analgesic efficacy and adverse effects of
intrathecal
nalbuphine, at
three
different
doses,(0.2mg,0.8mg,1.6mg)
and
intrathecal
morphine0.2mg for postoperative pain relief after
cesarean deliveries. They concluded that intrathecal
nalbuphine. 0.8 mg to 1.6 mg improve quality of
intraoperative analgesia with faster onset of pain
relief than morphine and provides good early
postoperative analgesia without µ receptor related
side effects5. A randomized, double-blind study to
evaluate the effects of intrathecal nalbuphine (200
μg and 400 μg )with hyperbaric 0.5% bupivacaine
in lower abdominal, urologic and lower limb
surgeries on 75 patients of either sex . Two segment
regression time of sensory blockade and duration of
analgesia were maximally prolonged with
nalbuphine 400 μg.with minimal effects over
hemodynamic and respiratory parameters6. The
effect of addition of nalbuphine to bupivacaine used
for elderly patients undergoing surgeries under
spinal anaesthesia in patients scheduled for lower
abdominal and lower extremity surgeries concluded
that nalbuphine provided post operative analgesia
for 8-9hrs without any adverse effects7. Previous
studies have demonstrated that visceral analgesia is
mediated by both µ and k receptors and that
intrathecal Nalbuphine suppresses response to
visceral pain5,8..Women report higher pain levels or
exhibit less tolerance than men for a given stimulus
intensities and k opioid analgesia is greater in
females than males9 which implies that k agonist
drugs like Nalbuphine can be used to control the
visceral pain caused by hysterectomy. Thus we
decided to undertake this randomised study to
evaluate the effects of intrathecal nalbuphine 1mg in
patients undergoing abdominal hysterectomy. There
was no significant difference in the onset of sensory
block between the two groups. The Time taken for
two segment regression of level, from highest
sensory level was 77.33 ± 9.35 minutes in Group B
as compared to 98.16 ± 9.86 minutes in Group BN,
the difference being statistically highly significant
(p<0.001). Duration of sensory block was measured
by regression time to L1 Level, It was 153.33 ±
25.33 minutes in GroupB, whereas it was 242.5 ±
22.46 minutes in Group BN. Thus it was prolonged
in group BN than in group B and the difference was
statistically highly significant. By its agonist action
nalbuphine stimulates K receptors which inhibits the
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release of neurotransmitters like substance P that
mediate pain. It acts as a post synaptic inhibitor on
the interneurons and output neurons of the
spinothalamic tract which transport nociceptive
information10. The duration of effective analgesia in
Group B was 180.83 ± 25.90minutes, while in group
BN, it was 302.4 ± 27.59minutes. So the duration of
effective analgesia was prolonged in group BN than
in group B and difference was statistically highly
significant. Opioid receptor activation reduces
intracellular cAMP formation and open potassium
channels( mu and delta ) or suppresses voltage gated
N type calcium channels ( kappa receptors ). These
actions result in neuronal hyperpolarisation and
reduced availability of intracellular calcium which
decreases neurotransmitter release by CNS and
myenteric neurons.11 thereby prolonging the
duration of effective analgesia. On statistical
analysis, patient belonging to group B complained
of pain earlier than that of group BN. Patients who
received bupivacaine with nalbuphine had
significantly longer duration for first request of
analgesia when compared to patients who received
bupivacaine alone with p Value (<0.001) which is
highly significant. On inter and intra group
comparison, there were no significant changes in
pulse rate at any time during intra operative period.
However the fall in blood pressure did occur but
was not of the grade of hypotension i.e. change in
blood pressure of < 20% of base line value and
hence, this fall in blood pressure is considered as
physiological
fluctuations
only.
Intergroup
comparison showed no statistically significant
value. In our study, there was no significant change
in Respiratory rate in intra operative and post
operative period in both the groups. Nalbuphine
exhibits ceiling effect for respiratory depression12,13
.Since respiratory depression is predominantly μ
receptor mediated effect and nalbuphine is a μ
receptor antagonist, respiratory depression effect is
expected to be attenuated by nalbuphine. None of
the patients had other µ related side effects like
urinary retention, constipation, pruritis etc.
CONCLUSION
In conclusion addition of Nalbuphine in the dose of
1mg to intrathecal hyperbaric bupivacaine 0.5%,
in patients undergoing abdominal hysterectomy;
Prolongs the two segment regression time, duration
of Sensory block and duration of Post operative
analgesia
along
with
maintaining
stable
hemodynamic and respiratory parameters without
any significant perioperative complications. Thus,
we conclude that Nalbuphine can be used as an
effective adjuvant along with intrathecal hyperbaric
bupivacaine to provide a pain free post operative
interval.
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