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J Anaesth Clin Pharmacol 2004; 20(3): 251-254 251

Comparison of Butorphanol and Fentanyl for Balanced Anaesthesia

in Patients Undergoing Laparoscopic Cholecystectomy

Hammad Usmani, A. Quadir, S.N. Jamil, Nitin Bahl, Amjad Rizvi

ABSTRACT

Equianalgesic doses of butorphanol (40mcg kg-1) and fentanyl (2.0mcg kg-1) were compared in 60 adult female
patients (ASA I and II) undergoing laparoscopic cholecystectomy under general anaesthesia. The patients were
divided into two groups of 30 each (n=30). One of the study drugs (butorphanol or fentanyl) were given just prior to
induction of anaesthesia in a double blind fashion. Following induction with a standard dose of propofol and tracheal
intubation using vecuronium bromide, anaesthesia was maintained with nitrous oxide-oxygen and titrated concentration
of halothane to keep the heart rate and blood pressure ±20% of base line. The proportion of patients with moderate-
severe pain during postoperative period was significantly higher in fentanyl group as compared to butorphanol
group. Time to first rescue analgesic (tramadol hydrochloride) was also significantly prolonged in butorphanol group
as compared to fentanyl group. The incidence of side effects was comparable in both the groups. Thus, butorphanol
is an effective analgesic for patients undergoing laparoscopic cholecystectomy under general anaesthesia.

KEY WORDS : Anaesthesia : Balanced

Analgesics : Butorphanol, Fentanyl
Pain : Postoperative
Surgery : Laparoscopic cholecystectomy

Narcotic analgesics are widely used as adjuvants METHODS

to anaesthetic agents, as part of a balanced anaesthetic
technique. They act to smoothen the intraoperative
course and decrease the requirements for other
anaesthetic agents, as well as to minimize postoperative
pain with minimal undesirable side effects.
Butorphanol is a morphinan chemically related to
levorphanol, a potent synthetic agonist-antagonist
narcotic; 1-3 while fentanyl is a short acting synthetic
opioid agonist.4,5
The purpose of this study was to compare
equipotent moderate doses of two different analgesics
i.e. butorphanol and fentanyl in healthy adult females
undergoing elective laparoscopic cholecystectomy under
general anaesthesia.
After approval from departmental ethics committee
and a written informed consent from the patients. A
randomized, double blind study was conducted on 60
ASA I & II females, planned for elective laparoscopic
cholecystectomy under general anaesthesia. The patients
were divided into two groups, of 30 each. All patients
were premedicated with midazolam 20mcg kg -1
intravenous injection (iv) and metoclopramide
0.15mg kg -1 iv. Two minutes before induction of
anaesthesia, patients received equianalgesic doses of
either butorphanol (40mcg kg-1) or fentanyl (2.0mcg kg-1)
as intravenous injection, given in a double blind fashion.
Induction of anaesthesia was done with propofol
2mgkg-1iv followed by tracheal intubation facilitated
with vecuronium bromide 0.1mgkg-1 iv. Anaesthesia was
maintained with 60% nitrous oxide in oxygen, halothane

Drs. Hammad Usmani, S.N. Jamil, Lecturers, A. Quadir, Reader, Nitin Bahl, Resident, Department of
Anaesthesiology, Amjad Rizvi, Lecturer, Deptt. of Surgery, J.N. Medical College, A.M.U. Aligarh (U.P.) INDIA.
Correspondence : Dr. Hammad Usmani.

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USMANI H; ET AL: BUTORPHANOL VS FENTANYL : FOR BALANCED ANAESTHESIA 252

(0.5%) and top up doses of vecuronium bromide. test for nonparametric data were used for statistical
Whenever there was an increase in heart rate (HR) or analysis. A p value <0.05 was considered significant.
mean arterial pressure (MAP) from the preoperative
baseline values, concentration of halothane was increased RESULTS
to 1%-2% to keep the HR and MAP within 20% of The two groups were comparable with respect to
baseline value. At the end of procedure, residual age, weight, height of the patients and duration of
neuromuscular blockade was reversed with neostigmine surgery or anaesthesia (table 1). During the
0.04mgkg-1 iv and atropine 0.02mgkg-1 iv. intraoperative period, mean concentration of halothane
required to keep HR and MAP ± 20% of baseline
Ventilation was mechanically controlled throughout
value, was significantly less in butorphanol group as
the operation. Arterial blood pressure (non-invasive),
compared to fentanyl group (table 1). Three patients in
heart rate (ECG), oxygen saturation (SpO2) via pulse
butorphanol group had sinus bradycardia, which was
oximetry, EtCO2 (capnography) were measured before,
managed by ceasing the inhalation of halothane for few
during and after anaesthesia at an intervals of 5-15
minutes and injection atropine 0.02mgkg-1 iv. Recovery
mins and until stable in the recovery room.
times measured from the time nitrous-oxide was stopped,
Two different recovery times were noted: time to as shown in table 2. The differences in the recovery
orientation (by asking name, place or birth date of the times between the two groups were not statistically
patient) and time to discharge from the recovery room significant (p>0.05).
to the surgical ward; measured from cessation of
inhalation anaesthetics (halothane and nitrous oxide). Table 1.
The standard discharge criteria (Wetchler criteria)6 were
Demographic Profile
used: fully awake and alert, no respiratory distress, gag
and cough reflex present, stable vital signs (blood Butorphanol Fentanyl
pressure, pulse rate, respiratory rate), minimum or no (Mean±SD) (Mean±SD)
nausea, no active bleeding. Age (yrs) 42.0 ± 13 45.0 ± 11
The frequency of side effects e.g. nausea, vomiting, Weight (kg) 52.0 ± 7 55.0 ± 12
drowsiness and dizziness were noted following direct Height (cms) 165.0 ± 5 162.0 ± 6
questioning of the patients in the recovery room. Surgery time (mins) 38.0 ± 13.0 40.0 ± 12.0
Drowsiness was assessed7 on a scale of 1 to 5, where 1 Anaesthesia time (mins) 85.0 ± 19.0 80.0 ± 13.0
Halothane concentration (%) *0.7 ± 0.4 1.1 ± 0.5
is no drowsiness and 5 is equal to unresponsive. Grades
4 or 5 were considered excessive drowsiness. Pain in *p<0.05 (unpaired ‘t’ test)
the recovery room was graded subjectively as none,
mild, moderate or severe. Rescue analgesic (tramadol Table 2.
hydrochloride, 1.5mgkg-1 intravenous injection) was Recovery time and time to first rescue analgesic
administered to those complained of moderate to severe
pain. Parameters Butorphanol Fentanyl
(Mean±SD) (Mean±SD)
All patients were interviewed 24 hours after the
Recovery times (mins):
operation in the surgical ward to get the information
- to orientation 18.0 ± 6.0 17.0 ± 6.0
regarding their experiences of perioperative period. - to discharge 145.0 ± 18.0 140.0 ± 21.0
Patients selected from one of the following four options;
Time to first rescue analgesic *208 ± 69 178 ± 53
poor (1), fair (2), good (3), excellent (4). The (min)
investigator who did all these evaluations was blind to Patients with moderate- *5 (17%) 12 (40%)
the group assigned. severe pain
in the recovery room (n,%)
Two way analysis of variance (ANOVA) and
student’s t-test for parametric data and the chi square *p<0.05 (unpaired ‘t’ test), *p<0.05 (chi square test).
J Anaesth Clin Pharmacol 2004; 20(3): 251-254
Postoperatively, there were no significant
differences in pulse rate, blood pressure and respiratory
rate between the groups. Postoperative side effects were
elicited by direct questioning of the patients. Responses
are shown in table 3. Incidence of nausea and vomiting
was slightly higher in butorphanol as compared to
fentanyl group, but the difference was insignificant (chi
square test, p>0.05)
Table 3.
Incidence of Postoperative Side Effects
Parameters Butorphanol
(n=30)
Nausea 9 (30.0%)
Vomiting 6 (18.0%)
Drowsiness
(grades 4 & 5) 7 (23.0%)
Dizziness 7 (23.0%)
*p<0.05 (chi-square test)
Excessive drowsiness (grades 4 or 5) was present
in 7 patients in butorphanol group and in 5 patients in
fentanyl group; one hour after admission to the recovery
room. However, there was no episode of hypoxemia
(SpO2<90%) or respiratory depression (respiratory rate
<8min-1) in any of the patients in two groups. Occurrence
of dizziness was more or less similar in both the groups.
Significant postoperative pain (moderate to severe)
in the recovery room was experienced by 12(40%)
patients receiving fentanyl and in only 5(17%) patients
in butorphanol group (p<0.05) (table 2). Mean time to
rescue analgesic administration was also significantly
prolonged in butorphanol group as compared to fentanyl
group (table 2). During follow up, the next day of
surgery; 72% of patients in butorphanol group and 57%
of patients in fentanyl group rated their experience as
good or excellent (fig 1).
DISCUSSION
The characteristic which distinguish butorphanol
and fentanyl is related to their opioid receptor spectra.
Butorphanol is a kappa-receptor agonist as well as weak
mu-receptor antagonist, whereas fentanyl is
predominantly a mu-receptor agonist.
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253
Excellent
Good
Fair
Poor
Fentanyl 7 36 50 7
Butorphanol 5 23 60 12
100 50 0 50 100
Proportion of patients (%)
Fig 1. Patient’s global evaluation of study medication
Fentanyl
In this study, we used equipotent moderate doses
(n=30)
of each agent which has been used routinely by most of
7 (23.0%) the anaesthesiologists.5,8 A low (0.5%) concentration of
5 (17.0%) halothane was added from the beginning of procedure
to keep a proper plane of anesthesia, without the
(5 (17.0%)
problems of prolong recovery time.
6 (18.0%)
Average duration of surgery in our study was 38-
40 mins, which corresponded to the duration of the
analgesic effect of butorphanol9 and fentanyl.9 Hence
use of a single bolus dose of these opioid analgesics
was justified.
Patients in butorphanol group demonstrated better
protection against autonomic stimulation to tracheal
intubation and surgical incision; as there were no
significant fluctuations in haemodynamic parameters
throughout the intraoperative period. This is consistent
with the previous reports by Pandit et al.5 and Philip et
al.10 In contrast to this, patients in fentanyl group
required increased concentration of halothane to keep
H.R and M.A.P ± 20% baseline values.
Butorphanol, due to its action on kappa-receptors
is associated with more sedation.9 However, in this study;
incidence of drowsiness in fentanyl group was as
comparable as in butorphanol group. This was due to
higher concentration of halothane required for
maintenance of anaesthesia in fentanyl group as
compared to butorphanol group. The discharge time of
patients from the recovery room was similar in both the
groups.
Complaint of postoperative pain was far less
frequent in butorphanol group as compared to fentanyl
253
USMANI H; ET AL: BUTORPHANOL VS FENTANYL : FOR BALANCED ANAESTHESIA
group. Rapid redistribution of fentanyl11 likely explains
this difference.
The incidence of nausea and vomiting in this study
was not as high as reported by Pandit et al.5 This could
be due to the use of prophylactic antiemetic therapy. It
is generally believed that female patients undergoing
laparoscopic procedures are more likely experience
nausea/vomiting postoperatively.12,13 Use of opioid
analgesics as part of anaesthetic management is a known
cause for this.14,15 Therefore, we recommend use of
prophylactic antiemetic therapy in all patients undergoing
laparoscopic cholecystectomy.
Our findings suggest that butorphanol is a better
choice than fentanyl for use in balanced anaesthetic
technique because of its ability to produce prolonged
analgesia and amnesia, stable haemodynamic
parameters, no postoperative respiratory depression
without prolonging the recovery room stay.
REFERENCES
1. Pircio AW, Gylys JA, Cavanaugh RL, Buynbiski
JP, Bierwagen ME. The pharmacology of
butorphanol, a 3, 14-dihydroxy-morphinan narcotic
antagonist analgesic. Arch Int Pharmacodyn Ther
1976; 220: 231-57.
2. Vandam LD. Butorphanol. N Eng J Med 1980; 302:
381-84.
3. Roscow CE. Butorphanol in perspective. Acute Care
1988; 12 (Supp 1): 2-7.
4. Mather LE. Clinical Pharmacokinetics of fentanyl
and its newer derivatives. Clin Pharmacokinet 1983;
8: 422-46.
5. Pandit SK, Kothary SP, Pandit UA, Mathai MK.
Comparison of fentanyl and butorphanol for
outpatient anaesthesia. Can J Anaesth 1987; 34: 2,
130-33.
254
6. Wetchler BV. Problem solving in postanesthesia care
unit. Anesthesia For Ambulatory Surgery. Edited
by BV Wetchler, Philadelphia, JB Lippincott Co.,
1985.
7. Pandit SK, Heisterkamp DV, Cohen PJ. Further
studies of antirecall effect of lorazepam. A dose-
time-effect relationship. Anesthesiology 1976; 45:
495-500.
8. Wetchler BV, Alexander CD, Shariff MSY, Gaudzels
GM. A comparison of recovery in outpatients
receiving fentanyl versus those receiving
butorphanol. Journal of Clinical Anesthesia 1989;
1: 339-43.
9. Gutstein HB, Akil H. Opioid analgesics. In: Gilman
AG, Hardman JG, Limberd LE (Eds) The
Pharmacological Basis of Therapeutics. 10th ed. New
York. McGraw-Hill Co., 2001; 569-620.
10. Philip RK, Scott AD, Freiberger D, Gibbs RR, Hunt
C, Murray E. Butorphanol compared with fentanyl
in general anaesthesia for ambulatory laparoscopy.
Can J Anaesth 1991; 38: 2, 183-86.
11. McClain DA, Hug C. Intravenous fentanyl Kinetics.
Clin Pharmacol Ther 1980; 28: 106-14.
12. Dhamee MS, Gandhi SK, Callen KM et al.
Morbidity after outpatient anesthesia- a comparison
of different anesthetic techniques for laparoscopy.
Anesthesiology 1982; 57: A 375.
13. Dawson B, Reed WA. Anaesthesia for day-care
surgery: a symposium III. Anaesthesia for adult
surgical outpatients. Can Anaesth Soc J 1980;
24: 409.
14. Dundee JW, Kirwan MJ, Clarke RSJ. Anesthesia
and premedication as factors in postoperative
vomiting. Acta Anaesthesiol Scand 1965; 9: 223-31.
15. Clarke RSJ. Nausea and Vomiting. Br J Anaesth
1984; 56: 19-27.