ANZ J. Surg.

2004; 74: 573–576

ORIGINAL ARTICLE
ORIGINAL ARTICLE

COMPARISON OF THE EFFECT OF DICLOFENAC WITH

HYOSCINE-N-BUTYLBROMIDE IN THE SYMPTOMATIC TREATMENT
OF ACUTE BILIARY COLIC

ANUP KUMAR, JAGPREET S. DEED, BHARAT BHASIN, ASHOK KUMAR AND SHAJI THOMAS
Department of Surgery, Lady Hardinge Medical College, Shaheed Bhagat Singh Marg, New Delhi, India

Background: Although non-steroidal anti-inflammatory drugs (NSAID) and spasmolytics have been used to relieve biliary colic,
the role of these drugs in the natural history of biliary colic has not been clarified. The objective of the present study is to compare the
efficacy of intramuscular diclofenac with intramuscular hyoscine in the treatment of pain of acute biliary colic, and to study their role
in the natural history of biliary colic and in the prevention of cholelithiasis-related complications.
Methods: Seventy-two consecutive patients with biliary colic were enrolled in this prospective, randomized, double-blind study.
They received either a single 75 mg intramuscular dose of diclofenac (n = 36) or similarly administered 20 mg of hyoscine (n = 36).
Pain severity was recorded on a visual analogue scale 30 min, 1 h, 2 h and 4 h after injection of the drug. Patients were then followed
closely for the next 72 h for persistence or relapse of pain, or development of acute cholecystitis, or drug related complications.
Results: Diclofenac provided much more rapid relief of pain than hyoscine, as shown by significantly lesser pain scores after
injection of the drug. 91.7% of patients on diclofenac were completely relieved of pain at 4 h as compared to 69.4% with hyoscine
(P = 0.037). Progression to acute cholecystitis was seen in only 16.66% of patients on diclofenac as compared to 52.77% on hyoscine
(P = 0.003).
Conclusions: In patients with biliary colic, diclofenac gives much faster and more effective pain relief in a significantly larger
number of patients as compared with hyoscine. Most remarkably, diclofenac can prevent progression of biliary colic to acute chole-
cystitis in a significant number of patients.

Key words: biliary colic, cholecystitis, cholelithiasis, diclofenac, hyoscine-N-butylbromide.

Abbreviations: CBD, common bile duct; LHMC, Lady Hardinge Medical College; NSAID, non-steroidal anti-inflammatory
drug; VAS, visual analog scale.

INTRODUCTION complications. The role of these drugs in the natural history of

Biliary colic is the most common manifestation of gall stone dis-
ease. About 75% of patients with symptomatic gall stone disease
seek medical attention because of episodic abdominal pain.1 After
an initial attack, 30% of patients have no further symptoms. The
remainder develop symptoms at a rate of approximately 6%/year
and severe complications at a rate of 1%/year.2,3
The symptomatic treatment of biliary colic is by using non-
steroidal anti-inflammatory drugs (NSAID), spasmolytics, or
the opiod group of drugs. The definitive treatment of recurrent
uncomplicated biliary colic in patients with gallstones is elective
cholecystectomy.1
In patients with biliary colic, it is not only the pain that
requires therapy, as impaction of gallstones or their passage
through the biliary tree often causes severe complications. To be
effective, any non-invasive treatment has to result in a decrease
of the frequency of complications, some of which can be life
threatening. In patients with biliary colic, a clinically relevant
issue is whether prostaglandin inhibitors like NSAID, or spasmo-
lytic drugs can prevent some or all of the cholelithiasis-related
A. Kumar MB BS, MS; J. S. Deed MS, DNB; B. Bhasin MB BS, MS;
A. Kumar MB BS, MS; S. Thomas MS, DNB.
Correspondence: Professor Shaji Thomas, C 44, Shivalik Colony, Malviya
Nagar, New Delhi 110017, India.
Email: drshajithomas@yahoo.com
Accepted for publication 4 December 2003.
biliary colic has not been clarified. There have been very few
such comparative studies in the past, and follow up was limited.4,5
The present prospective, randomized, double-blind study was
done to compare the efficacy of diclofenac, a potent present gen-
eration NSAID with strong anti-prostaglandin activity, and hyo-
scine in the symptomatic relief of biliary colic as well as on the
progression to other cholelithiasis related short-term complications.
PATIENTS AND METHODS
The present prospective randomized study was conducted at the
Department of General Surgery, Lady Hardinge Medical College
(LHMC), New Delhi, India. Seventy-two consecutive patients
with biliary colic attending the Emergency services of LHMC
were enrolled in the study. Only patients with biliary colic pre-
senting with severe pain of less than 6 h duration were included
in the study.
Excluded from the study were patients with severe pain
lasting more than 6 h, fever, leucocytosis, deranged liver func-
tion tests, signs of peritonitis or ultrasound evidence of acute
cholecystitis or common bile duct (CBD) stones. Also excluded
from the study were patients who had received analgesics or
antibiotics before hospital presentation, and those with preg-
nancy or significant systemic diseases like diabetes mellitus,
uremia, cardiovascular or respiratory disease. Similarly,
patients with contraindications for receiving diclofenac (acute
peptic ulcer, gastrointestinal bleeding, asthma or NSAID
induced allergy) or hyoscine (glaucoma, prostatic hypertrophy
574 KUMAR ET AL.

with urinary retention, gastrointestinal mechanical stenosis,
porphyria) and those receiving medications likely to have adverse
interactions with diclofenac or hyoscine (lithium, digoxin, L-
Dopa, antidepressants, phenothiazines) were also excluded from
the study.
The study population underwent detailed clinical evaluation
and baseline haematological and biochemical parameters, includ-
ing complete haemogram, blood urea, blood sugar and complete
liver function tests. The presence of gallstones was confirmed by
ultrasonography.
The patients were randomized into two groups: group A or
group B by the randomized block design. Patients in group A
received a single dose of 75 mg of injection diclofenac given
deep intramuscularly, and group B received a single dose of
20 mg of injection hyoscine-N-butylbromide. In both the groups,
pain severity was recorded on a 10-point visual analog scale
(VAS) 30 min, 1 h, 2 h and 4 h after the injection.
Patients were then followed closely for the next 72 h for the
persistence or relapse of pain, or the development of acute chole-
cystitis (which was confirmed by ultrasonography). The results
were then analysed statistically.
OBSERVATIONS
The patients varied in age from 19 to 60 years. The mean age of
patients in group A did not differ significantly from that in group
B (41.97 years ± 11.56 years, 40.75 years ± 12.34 years, P = 0.66
using student’s T-test). The mean weight of the patients (range
32–75 kg) was also not significantly different between the two
groups (52.5 ± 11.6 kg, 51.25 ± 12.4 kg, P = 0.725 using stu-
dent’s T-test). The duration of the past history of episodes of pain
was 1.34 ± 1.25 years in group A and 1 ± 1.17 years in group B,
which was also not significantly different (P = 0.24 using stu-
dent’s T-test). The duration of present episode of biliary colic on
presentation to the hospital was 3.94 ± 1.47 h (range 2–7 h) in
group A, and 4 ± 1.28 h (range 2–6 h) in group B, there being
no statistically significant difference between the two groups
(P = 0.865, student’s T-test)
The intensity of pain recorded using VAS at 0 min, 30 min,
1 h, 2 h, and 4 h after injection of the drug in the two groups is
shown in Table 1. As evident, the mean pain scores were signifi-
cantly lower in the group receiving diclofenac as compared to
those receiving hyoscine at all the above time intervals.
From Table 2, it can be seen that none of the patients were
completely relieved of pain within 1 hour of receiving either
injection. However, the number of patients completely relieved of
pain at 2 h after injection was significantly more in the group
receiving diclofenac as compared to the group receiving hyoscine
(20 vs 7, P = 0.0035 χ2-test). Similarly at 4 h after injection, the
total number of patients completely relieved of pain was signifi-
cantly more in the diclofenac receiving group as compared to the
hyoscine receiving group (33 vs 25, P = 0.037 χ2-test).
The number of patients in whom pain persisted beyond 4 h of
injection was significantly less with diclofenac (Table 3). Also,

Table 1. Intensity of pain (on the visual analog scale (VAS)) at different intervals of time after injection
Time interval Pain intensity on VAS P-value (Student’s t-test)
Group A (diclofenac) Group B (hyoscine)
Mean ± SD (range) Mean ± SD (range)

Before injection (0 min) 9.58 ± 0.54 (8–10) 9.61 ± 0.48 (9,10) 0.818 (not significant)
30 min after injection 5.15 ± 1.2 (2–7) 5.76 ± 0.97 (4–7) 0.02 (significant)
1 h after injection 2.29 ± 1.28 (0.5–5) 3.32 ± 1.13 (1–5) 0.001 (significant)
2 h after injection 0.625 ± 0.83 (0–3) 1.69 ± 1.09 (0–4) 0.0001 (significant)
4 h after injection 0.139 ± 0.48 (0–2) 0.556 ± 0.88 (0–2) 0.015 (significant)

Table 2. Number of patients completely relieved of pain during observation period

Time period Group A Group B P-value (χ2-test)
(Diclofenac, n = 36) (Hyoscine, n = 36)
No. patients (%) No. patients (%)
30 min 0 0
1h 0 0
2h 20 (55.55) 7 (19.44) 0.0035 (significant)
4h 33 (91.66) 25 (69.44) 0.037 (significant)

Table 3. Progression to acute cholecystitis

Group A Group B P-value (χ2-test)
(Diclofenac, n = 36) (Hyoscine, n = 36)
No. patients (%) No. patients (%)

Persistence of pain beyond 4 h 3 (8.3) 11 (30.6) 0.035 (significant)

Relapse of pain after 4 h 3 (8.3) 8 (22.2) 0.019 (not significant)
Progression to acute cholecystitis 6 (16.66) 19 (52.77) 0.003 (significant)
DICLOFENAC VERSUS HYOSCINE
patients relapsing with pain after getting relief were again much
less with diclofenac, but this difference was not statistically sig-
nificant. However, the most dramatic difference was seen in the
total number of patients progressing to full blown acute chole-
cystitis: while only 16.66% of patients on diclofenac went on to
develop this, the figure was as high as 52.77% in the group
receiving hyoscine (P = 0.003 χ2-test).
DISCUSSION
Gallstone disease affects 4–21.9% of the world’s population6 and
a prevalence rate of 6.12% has been reported from Northern
India.7 Although 75% of gallstones are asymptomatic,8 biliary
colic is the most common manifestation. After the initial attack,
30% have no symptoms while the remainder develop symptoms
at a rate of approximately 6%/year and severe complications at a
rate of 1%/year.2,3 Because of the high prevalence rate of gall-
stones, biliary colic contributes significantly to the admission
load of the emergency department of major hospitals all over the
world. The development of acute cholecystitis prolongs the dura-
tion of hospital stay and increases the bed occupancy. In develop-
ing countries, this is a strain on the already overburdened health
care services.
Biliary colic is caused by intermittent obstruction of the cystic
duct by one or more gallstones. When a gall stone is impacted at
Hartman’s pouch and the cystic duct obstructs, a cascade of
events is presumed to develop involving cellular injury and
release of lysosomal enzymes, phospholipases, lecithin and
prostaglandins, all of which cause an inflammatory process. This
cascade of mechanical and chemical reaction begins the progres-
sive process that culminates in acute cholecystitis.9 The crucial
process for development of calculus cholecystitis is the obstruc-
tion of the cystic duct either by stone or oedema. Prostaglandins
are particularly important mediators, since they enhance oedema
causing increased obstruction and increased smooth muscle
contractions.9–11
Diclofenac is a newer arylacetic acid derivative, an analgesic,
antipyretic, anti-inflammatory drug and is more potent then
indomethacin and several other NSAID.12 It inhibits cyclooxyge-
nase and thus inhibits prostaglandin synthesis. Prostaglandins are
responsible for producing hyperemia, oedema and smooth muscle
contraction, thus causing biliary colic and cholecystitis. Anti-
prostaglandins have a double role: they slow the chemical process
leading to inflammation, and block the mechanical process of
biliary stone entrapment and cystic duct obstruction by prevent-
ing smooth muscle contractions. Therefore diclofenac has anti-
colic and antibiliary inflammation properties.13 It reduces raised
intraluminal gall bladder pressure in cholecystitis, and thus has a
favourable effect on the clinical course of acute cholecystitis.14
A single dose of intramuscular diclofenac can provide satis-
factory pain relief and might decrease the rate of progression to
acute cholecystitis.15
Todd and Sorkin, in a controlled clinical trial, suggested that
diclofenac is the NSAID of choice in treatment of acute biliary
colic as dose adjustments in the elderly are not required, has a fast
onset and long duration of action and was superior to many nar-
cotics and spasmolytic combinations in biliary colic.16 When
administered intramuscularly it rarely produces gastrointestinal
ulceration or other serious side-effects.16 Diclofenac also inhibits
diet induced gall stone formation17 and also prevents gallstone
formation by its prokinetic effect on the gallbladder18 and by
decreasing bile viscosity.19
575
Anticholinergic drugs (spasmolytics) are extensively used in
several conditions with pain from increased gastrointestinal tone
or motility. Biliary colic pain shows an increased intraluminal
pressure in gall bladder and biliary tract because of smooth
muscle contraction. Hyoscine reduces the tone, amplitude and
frequency of smooth muscle contractions and has been shown to
have an antispasmodic action on the gallbladder and bileducts.20
Antispasmodic drugs have been shown to be useful in the treat-
ment of biliary colic.21 De Los Santos et al. in 1999, found a
dose-related efficacy of the antispasmodic propinox in relieving
acute biliary pain.22 The role of spasmolytics in the prevention of
progression of biliary colic to acute cholecystitis is not known.
A few studies recently indicate that NSAID might prevent
progression of acute biliary colic to acute cholecystitis. Akrivi-
adis et al. in 1997 concluded that when compared to placebo,
diclofenac provided satisfactory pain relief and could reduce
the progression to acute cholecystitis.15 A study conducted by
Al-Waili and Saloom in 1998, found i.v. tenoxicam (an NSAID)
superior to hyoscine in acute biliary pain and in preventing its
progression to acute cholecystitis.4 Because NSAID, by inhibit-
ing prostaglandin synthesis, could cause relief of any pain regard-
less of its origin, the result of the previous studies, particularly the
effect on progression to acute cholecystitis, needed to be vali-
dated by longer follow-up, which would provide data on whether
NSAID have the potential to prevent the complications of biliary
colic. Although it has been shown that laparoscopic cholecystec-
tomy can be performed with safety in the presence of acute chole-
cystitis, the procedure tends to be technically more demanding,
with increased morbidity, prolonged operating time and higher
conversion rates.23,24 Therefore, the prevention of a ‘hot’ gall-
bladder is an important therapeutic goal, even in the era of wide-
spread acceptance of laparoscopic cholecystectomy.
In our prospective, randomized, double-blind study, the
patients received either diclofenac or hyoscine and were hospital-
ized for 72 h. There was no statistically significant difference in
the mean age, weight, duration of past history of pain, and dura-
tion of present episode of pain between the two groups. Intra-
muscular administration of diclofenac provided symptomatic
pain relief in a larger group of patients than with intramuscular
hyoscine (91.7% vs 69.4% at 4 h). Diclofenac also provided more
rapid relief than hyoscine as evident by significantly lesser pain
scores at 30 min, 60 min, 2 h and 4 h duration after injection. Per-
sistence of pain beyond 4 h, as well as relapse of pain was also
significantly less with diclofenac. In addition to its immediate
symptomatic effect, diclofenac appears to have an important
impact on the natural history of biliary colic. Significantly less
number of patients (16.6%) progressed to acute cholecystitis after
receiving diclofenac than those who received hyoscine (52.77%).
While the most appropriate definitive treatment for sympto-
matic gallstones is surgery, the initial clinical management of
biliary colic should be to provide for symptomatic relief of pain
and also to prevent the development of cholelithiasis-related
complications. Acute cholelithiasis is the most common of these
complications leading to significant morbidity and prolonged
hospital stay. Our study shows that diclofenac provides signifi-
cantly faster symptomatic relief and, most remarkably, also pre-
vents progression to acute cholecystitis in a significant number
of patients as compared to hyoscine. We recommend the use of
prostaglandin inhibitor (diclofenac) in all biliary colic attacks and
in high-risk patients when surgery should be either postponed
or avoided. Elective cholecystectomy could then be easily
accomplished.
576
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