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OJHAS Vol. 9, Issue 3:
(Jul - Sep, 2010) |
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| Butorphanol for Post-Operative Analgesia - A Comparative Clinical Study with Ketorolac |
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Thrivikrama
Padur Tantry, Associate
professor, Department of
Anaesthesiology,
Nandish S Vastrad, Junior resident, Department of Anaesthesiology
Reshma
Koteshwar, Post
graduate resident, Department of
Anaesthesiology,
Prashanth Mohan, Assistant professor, Department of
Orthopedics,
Rajani Kadri, Assistant
professor, Department of
Ophthalmology,
Dinesh Kadam, Professor, Department of
Plastic & Reconstructive surgery,
Karunakara Adappa, Professor and Head, Department of
Anaesthesiology,
Sunil P Shenoy, Professor, Department of
Urology,
AJ Institute
of Medical Sciences, Kuntikana, Mangalore -575004, India. |
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Address For Correspondence |
Associate
professor,
Department of Anaesthesiology,
AJ Institute
of Medical Sciences,
Kuntikana, Mangalore - 575004, India.
E-mail:
drpttantry@yahoo.com |
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Tantry TP, Vastrad NS, Koteshwar R, Prashanth Mohan, Kadri R, Kadam
D, Adappa K, Shenoy SP. Butorphanol for Post-Operative Analgesia - A Comparative Clinical Study with Ketorolac. Online J Health Allied Scs.
2010;9(3):9 |
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Submitted: Sep 10, 2010;
Accepted:
Sep 29, 2010; Published: Oct 15, 2010 |
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| Abstract: |
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Introduction:
Butorphanol, an opioid derivative has been shown to have, in addition
to its analgesic properties, several other advantageous effects like
antistressor, sedative and anti-shivering action. The efficacy and safety
profile of ketorolac, yet another widely used post-operative analgesic
is well documented. This study aims to compare the two analgesics. Aims
and objectives: This study was conducted to compare the analgesic
efficacy and other effects of butorphanol and ketorolac, administered
intramuscularly, in post-operative patients who have undergone lower
abdominal and pelvic surgeries. Materials
and methods: 50 patients undergoing lower abdominal and pelvic surgeries
under general or spinal anaesthesia were randomly divided into two Groups
(25 each). At a particular level of post-operative pain, the patients
Groups I and II were administered intramuscular ketorolac 30mg and butorphanol
2mg respectively. The analgesic effect was studied using Visual Analogue
Scale (VAS) and the verbal category scale. Patients were monitored for
the sedative action, respiratory status and other vital parameters for
300 minutes and for other adverse reactions over the next twelve hours. Observations:
Butorphanol provided better analgesia within the first two hours of
administration, while ketorolac was more effective at 4-5 hours. Better
sedative action without any significant respiratory depressant effect
was demonstrated with butorphanol. There were no clinically significant
hemodynamic fluctuations or adverse reactions with butorphanol or ketorolac. Conclusions:
Butorphanol provides better early analgesia as compared to ketorolac
with a desirable and safe sedative effect in post-operative patients
who have undergone lower abdominal and pelvic surgeries.
Key Words: Acute post operative pain; Butorphanol; Ketorolac; Analgesia
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Inj.
ketorolac is extensively used for post-operative pain management.1
The effectiveness and safety profile of inj. ketorolac in patients undergoing
abdomino-pelvic or orthopaedic surgery are well documented.2,3,4
Parenterally administered butorphanol in doses of 2 to 3mg provides
analgesia equivalent to 10mg morphine or 80mg pethidine. Intra-operatively,
during the maintenance phase of general anaesthesia, butorphanol has
been shown to be superior to fentanyl.5
Apart from the primary aim of providing analgesia, several collateral
advantages of butorphanol like antistressor effect, sedation and ‘anti-shivering’
property have been described. 6,7
In
this randomized study, we compared the analgesic efficacy and other
effects of inj. butorphanol (study drug) with inj. ketorolac (control
drug) for post-operative pain relief in patients who underwent lower
abdominal and pelvic surgeries.
Aims and Objectives:
To
compare the analgesic efficacy and other effects of butorphanol and
ketorolac, administered intramuscularly, in post-operative patients
who have undergone lower abdominal and pelvic surgeries.
This
randomized study was approved by the Institutional Ethical Committee
of A. J. Institute of Medical Sciences. Fifty patients coming under
American Society of Anaesthesiologists (ASA) Class I and II categories
undergoing elective lower intra-abdominal open surgical procedures were
assigned randomly to one of the two groups – Group I being the control
(ketorolac) group and Group II, the study (butorphanol) group. These
included psychologically, biochemically and physically healthy patients
or patients with systemic disease like hypertension on regular treatment
and with the disease well under control. Exclusion criteria were age
over 60 years, ASA class III and IV, the mentally challenged, smokers,
alcoholics, and those with abnormal renal and liver function tests.
An
informed consent was taken on the pre-operative day. All the patients
were instructed on and explained the use of the Visual Analogue pain
Scale (VAS), and descriptor words of pain. Documentation of baseline
blood pressure, heart rate, respiratory rate, temperature and weight
was done. All patients were in fasting status and received either intravenous
inj. ranitidine 50mg, 1 hour before surgery or tab. pantoprazole, 40mg,
3 hours pre-operatively. No other pre-medication was used.
The assessment of the pain was carried out using the numeric VAS, and
verbal category scale (descriptor words of pain). Pain assessment charting
is explained below.
Visual
Analogue Scale (VAS): VAS is a 10cms line anchored at the two end
points, “no pain” and “pain as bad as it can be”. The patient
is asked to place a mark on this line indicating the intensity of his
pain. The VAS score is determined by measuring the distance in cms from
the end signifying “no pain” to the point indicated by the patient
on the scale.
Descriptor
/ verbal category scale: Verbal category scale consists of a series
of words subjectively describing pain intensity and unpleasant experiences.
The patient is asked to select one adjective that best describes his
/ her pain or feeling. As per the description, the patient is classified
into mild, moderate or severe pain categories, which are numbered 1, 2 or
3 respectively. ‘Mild’ includes terms such as tolerable, bearable,
just noticeable, mild, weak, and very weak. ‘Moderate’ encompasses
expressions such as unpleasant, uncomfortable, distressing, moderate,
and getting intense. Terms such as intolerable, agonizing, miserable,
strong, very intense and excruciating comprise the ‘severe’ category.
All these terms are explained and elicited in a language familiar to
the patient.
The
surgery was performed under general or spinal anaesthesia in all patients.
Patients taken up under general anaesthesia received a standard dose
of inj. fentanyl, 1 to 2 micrograms per kg intravenously and patients
in the spinal anaesthesia group received 0.5% of 2.5 to 3ml of heavy
bupivacaine. The time and dose of any additionally administered analgesic
like fentanyl, tramadol or diclofenac were documented. In the post anaesthesia
care unit, each patient was assigned randomly to one of the two predetermined
groups. Patients in Group 1 (n=25) received inj. ketorolac 30mg and
whereas those in Group II (n=25)
received inj. butorphanol 2mg. All injections were given intramuscularly
in the gluteal region.
The
initial time at which the patient developed VAS pain score of 2 or 3
after the surgical procedure was noted, the control or study drug administered
and monitoring commenced. Pain assessment was done at intervals of 30,
60, 120, 180, 240 and 300 minutes following administration of the analgesic
(ketorolac or butorphanol). Vital parameters like blood pressure, heart
rate, and respiratory rate were noted at similar intervals. Apart from
pain intensity, the sedation effect was assessed using a 4 point scale,
noting made at the same times as pain assessment (awake=0, mild drowsiness=1,
moderate drowsiness=2 and asleep=3). Patients were observed specifically
for clinical respiratory depression (low respiratory rate and narcosis)
with arterial blood gas analysis contemplated in clinically indicated
cases. Other side effects such as headache, nausea, vomiting, weakness,
giddiness, sweating, dyspepsia, pruritus and untoward pain at the injection
site were documented up to 12 hours after analgesic administration.
Criteria
for withdrawal of further monitoring:
Patients demonstrating VAS score of 7 or more at any time up
to the 300 minute recording, complaining of severe pain according to
the verbal category scale, or directly demanding additional analgesia
were administered intravenous inj. tramadol 50mg and withdrawn from
further observation from that point of time. Any patient suffering from
severe or refractory side effects within the 300 minute period was also
proposed to be withdrawn from further observation in the study.
Statistical
analysis: Data obtained is presented as mean ± standard deviation.
Patient demographics like age and weight were compared using Student’s
t test. Systolic and diastolic blood pressures, heart rate, respiratory
rate and time lag for VAS score of 2/3 were also compared using Student’s
t test. The VAS score, descriptor score, sedation and inter-group fluctuations
of vitals were compared using Mann-Whitney U test. A ‘p’
value less than 0.05 was considered as the minimum level for statistical
significance. All parameters documented except minor side effects like
nausea, vomiting etc were subjected to comparative statistical analysis.
Preoperative
vitals: All preoperative vitals were statistically comparable in
the two groups. The systolic blood pressure of Group I averaged 126.64±10.48
mmHg
versus Group II which showed 125.76±10.74 mmHg (p>.05). Diastolic
blood pressure of Group I was 73.12±10.08 versus 68.48±9.95 in Group
II (p>.05). The mean heart rate (beats per minute) in Group
I was 76±8 and that in Group II was 81±7 (p>.05). Similarly
respiratory rate was 14±1.7 in Group I versus 13±1.9 in Group II (p>.05).
Time
lag to develop a VAS score of 2/3 after the procedure varied significantly.
In Group I it was 57.80 ±41.005 minutes versus 38.60±27.595 in Group
II (p<.05).
Type
of anaesthesia: 17 patients in Group I received spinal anaesthesia
compared to19 in Group II. Rest of the patients in both the groups (32
percent versus 24%) received general anaesthesia. There was no statistical
differences between the groups (p>.05). While Inj. fentanyl
was used whenever indicated intra-operatively, no long acting analgesic
like diclofenac was administered to any patient in either Group.
Sedation
score: (Table 1) Mean sedation scores at 0 minute were comparable
in the two groups (p>.05). Recordings between 30th
and 180th minute showed significantly higher sedation values
in Group II versus Group I with the highest statistical significance
being of comparative readings taken at 60, 120 and 180 minutes (p<.005).
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Table
1: Distribution of descriptor
ratings of pain |
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Group I |
Group II |
| Time(min) |
n |
Mild |
Moderate |
Severe |
n |
Mild |
Moderate |
Severe |
| 30 |
25 |
12 |
13 |
0 |
25 |
7 |
17 |
1 |
| 60 |
25 |
20 |
4 |
1 |
24 |
16 |
7 |
1 |
| 120 |
24 |
17 |
6 |
1 |
23 |
16 |
7 |
0 |
| 180 |
23 |
19 |
4 |
0 |
23 |
14 |
8 |
1 |
| 240 |
23 |
18 |
5 |
0 |
22 |
8 |
10 |
2 |
| 300 |
23 |
14 |
7 |
2 |
22 |
7 |
8 |
5 |
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(p>.05) |
VAS
scores: Comparison of VAS scores between the two groups (Figure
1) revealed a significantly lower score at 60 and 120 minutes (p<.05)
in the butorphanol treated Group II as compared to the ketorolac treated Group
I. The scores showed no significant difference when earlier or later readings
were compared.
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Figure 1: Intergroup comparison of sedation
and VAS scores (mean±SD). |
Descriptor
pain rating: The distribution of descriptor ratings of pain is shown
in Table 1, ‘n’ indicating the number of patients observed in each
group at various intervals. Patients were excluded from study when they
termed the pain as ‘severe’. 4 patients of Group I complained severe
pain versus 10 patients of Group II during the 300 minutes period of
observation. The number of patients in each group, in each pain severity
category, at the predetermined time schedule was compared and no statistically
significant difference was found between the two groups (p>.05).
Comparison
of vitals: The systolic and diastolic blood pressures, mean
heart rates and respiratory rates in two groups following injection
of the respective analgesics was comparable (p>.05),(Figure 2, Figure 3). The only statistically significant difference observed
was as regards the respiratory rates at 30,60 and 90 minutes, which
were lower in Group II (p<.005), but this difference was observed even
at the onset (0 minute) when the analgesic was administered. There was no
instance of clinical respiratory depression in any patient.
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| Figure
2: Intergroup comparison of systolic and diastolic blood pressures(mean±SD) |
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Figure
3: Inter group comparison of heart rates and respiratory rates(mean±SD) |
Additional
analgesia: Up to 240 minutes (Table 2), 2 patients in Group I and
3 in Group II needed additional doses of intravenous Inj. Tramadol for
relief of ‘severe’ pain as per descriptor rating. Beyond this period,
in the last hour of study, 7 in Group II needed Inj. Tramadol as compared
to 2 in Group I. The differences observed before and after this cut
off period were however not statistically significant (p>.05
in both comparisons).
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Table
2: Number of patients
requiring additional analgesic doses of IV tramadol, inter group comparison. |
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n |
Group I |
n |
Group II |
| Up
to 240mins |
25 |
2 |
25 |
3 |
| After
240 mins |
25 |
2 |
25 |
7 |
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(p>.05) |
Other
adverse reactions: Nausea and vomiting were observed in 11 (44%)
patients of the ketorolac group and 15 (66%) patients of the butorphanol
group. Among the select patients who developed this reaction, 33% of
patients in the Control group and 36% in the Study group had been administered
Inj. tramadol. Other side effects were negligible in both the groups.
In
our randomized study, we were able to demonstrate the comparative analgesic
efficacy and safety profile of the study drug butorphanol vis-à-vis
a control drug ketorolac, both administered intramuscularly.
Mathews
KA et al8 compared inj. ketorolac with inj. butorphanol in
controlling post- operative pain following shoulder arthrotomies in
dogs. While the pain assessment parameters in animal studies are in
no way comparable to the VAS and verbal descriptive scores of our study
on humans, their study showed a lower efficacy of butorphanol in relieving
pain as compared to ketorolac.
Atkinson
BD et al9 in a double blind study comparing the analgesic
properties and outcomes of intravenous inj. butorphanol with inj. fentanyl
during labor, reported that butorphanol elicited better VAS scores than
fentanyl. In this study, pain was scored independently by the nurse
and patient with the VAS. The assessment of pain in our study was by
self reports of pain. These self reports are important components in
evaluating treatment effectiveness.10 Clinical researchers
have demonstrated that valid self reports of pain are useful in treating
patients suffering from acute or chronic pains.10
All our patients had VAS scores of
either 2 or 3 at the time of administering the analgesic injection.
The time lag for developing this score varied significantly between
the two study groups. This may be related to the type of anaesthesia
and the duration of the surgical procedure. Short procedures under spinal
anaesthesia afford a longer time lag as compared to longer procedures
under the same anaesthesia or any procedure under general anaesthesia.
Heavy bupivacaine 0.5%, the drug used for spinal anaesthesia has an average
duration of action of 2.5 hours after central neuraxial blockade. However this
time-lag factor should not affect the outcome of study since the analgesia was
administered and recording of parameters commenced only at a specific point (VAS
pain scores 2 or 3), when the anaesthetic effect would have worn out.
The
peak plasma concentration of the drugs after intramuscular injection
is achieved at 45 to 60 minutes with ketorolac and 60 to 90 minutes with
butorphanol.11 This factor might have resulted in
a relatively better score in both the groups in the early postoperative
period compared to the later. Between the two drugs however, specifically
at 60 minutes and 120 minutes, a statistically significant difference
between the VAS scores may suggest that butorphanol provides a better
initial pain relief as compared to ketorolac.
Up
to three hours after the VAS 2/3 point, majority of patients in both
groups reported mild pain symptoms. In the later part of the study (240
and 300 minutes), a much larger percentage of butorphanol treated patients
complained of moderate or severe pain and received additional Inj. tramadol.
Though statistical significance of this difference was not documented,
the findings point towards an earlier wearing out of the analgesic action
of butorphanol as compared to ketorolac. The observation is in accordance
with the documented plasma half lives of ketorolac (5 hours) versus butorphanol
(3 hours).12
Like
other opioids, butorphanol is known to cause sedation in doses of 1
to 2mg.13 Our study confirmed this attribute of butorphanol.
The statistically significant higher sedation scores observed in the
butorphanol treated group corresponded to the possible peak plasma concentrations
of the drug (60 to 180 minutes). At no occasion did the severity of sedation
evoke concern on the possibility of the patient going into respiratory
depression.12 Such sedation relieves surgery related anxiety,
provides the much needed comfort for a post-operative patient and should
therefore be considered a beneficial effect of the study drug. The minimal
though statistically significant drop in respiratory rates in the study
group within the first two hours could be attributed to the greater
sedative effect of butorphanol as compared to ketorolac.
Fluctuating
cardiovascular responses like tachycardia are noted with inadequate
analgesia. An effective analgesic prevents this response. The sedative
property of an analgesic like butorphanol could also dampen this effect.
Direct cardiovascular effects reported with butorphanol include increased
cardiac workload, a stable or increased blood pressure with a stable
heart rate.14 Phillip BK et al5 observed a fall
in heart rate and low diastolic pressures with intravenous administration
of butorphanol. It is fortuitous that we did not encounter
any serious or clinically significant fluctuations in haemodynamic parameters
within each group nor did we observe a difference in values between the two
groups. Had such effects been noted, it would have been difficult to assign the
relative contributions of such drug actions and the pain itself to the
observations.
A
higher incidence of nausea and vomiting was observed in our study group
patients as compared to the controls. Inj. tramadol itself induces vomiting
and its role in the aetiology of this adverse effect cannot be excluded.
However, in patients who developed post-operative nausea and vomiting,
the extent of use of Inj. tramadol was similar when the two Groups were
compared. This observation suggested a higher ‘nauseogenic’ and
emetic effect for butorphanol as compared to ketorolac. Opioids stimulate
the chemoreceptor trigger zone in the area postrema of the medulla possibly
through delta receptors, leading to nausea and vomiting.14
Early post-operative nausea and vomiting (PONV) is a known entity caused
by various factors including pain itself.15 Surgical causes of nausea
and vomiting, type and duration of surgery and other unidentified factors might
have contributed to this adverse effect.
The
possibility of interactions with other analgesic drugs used intra-operatively
and during the period before the commencement of assessment of study
parameters was seriously considered. Long acting analgesics like diclofenac
might play a significant role in influencing early post-operative pain
either due to their stand alone actions or due to their additive actions
with the study or control drug. However, patients in either Group, who
needed additional intra-operative analgesia, received only short acting
analgesics like inj. fentanyl.
Advantages
and limitations of our study: Our study design had an inherent advantage
in that no patient initially included after going by the exclusion criteria
needed to be totally withdrawn from the study. The data provided up
to the point of discontinuing monitoring either due to severe pain (high
VAS or descriptor verbal score) or refractory side effects could be
usefully documented and statistically analysed. However, there were
some pitfalls too. We used both the drugs in fixed doses; and differences
in body weight, volume of distribution, and individual metabolism could
have resulted in varying plasma levels of the drugs in different patients.
We did not measure the plasma levels of the analgesic drugs during the
study. Patient factors like psychological makeup and variations in pain
threshold might have had a bearing on our observations. The tissue trauma
related to the extent of surgery too may have had a contributory effect,
surgeries like appendectomy not truly comparable with more major pelvic
surgeries. Finally, the small numbers of patients in each group might
have limited the true clinical significance of our comparisons.
We compared intramuscular
Inj. butorphanol
to Inj. ketorolac for post-operative pain relief in patients who underwent
lower abdominal and pelvic surgeries. We were armed with the knowledge that butorphanol
is an opioid analgesic and may therefore provide adequate pain relief.
Apart from analgesia, butorphanol has other actions like sedation and
anti-shivering properties that may prove beneficial in the post-operative
period. At the same time, being an opioid, its respiratory depressant
property may pose a major problem. The study attempted to evaluate the
comparative efficacy and adverse reactions between the two drugs in
the post-operative period.
We
observed that butorphanol (2mg) produces better analgesia in the initial
2 hours after injection compared to ketorolac (30mg) while ketorolac
provided more effective analgesia in the later period of 4 to 5 hours
following injection. Butorphanol produces better sedation without any
significant respiratory depressant effects. Like ketorolac, butorphanol
has little effect on cardiovascular hemodynamics. A relatively higher
incidence of nausea and vomiting following its administration can be
treated effectively. Intramuscular butorphanol can be used effectively and
safely for post-operative pain relief in doses of 2mg for minor to moderate
lower abdominal and pelvic surgeries. However the usage of the drug in similar dosage for
major surgeries needs further evaluation.
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