Anaesth Intensive Care 2009; 37:
Remifentanil-induced abdominal pain: a randomised clinical
S. JAHANbAKHSH*, A. bAMESHKI*, P. KHASHAyAR†
Anesthesiology Department, Imam Reza Hospital, Tehran, Iran
Remifentanil is an ultra-short-acting opioid, widely used for induction and maintenance of anaesthesia in various
types of operations. We recently noted that a great number of patients receiving remifentanil in their anaesthetic
regimen experienced postoperative abdominal pain. As a result, we performed this study to investigate its incidence.
This randomised single-blinded clinical trial was conducted on 300 patients who were undergoing elective
cataract surgery under general anaesthesia. The patients were randomly divided into two groups. In the control
group (n=150), anaesthesia was induced with fentanyl and propofol and maintained by propofol by infusion and
60% N2O. In the remifentanil group, anaesthesia was induced with remifentanil and propofol and maintained by
remifentanil infusion and 60% N2O inhalation. Atracurium was used for muscle relaxation in both groups.
Abdominal pain was observed in 79 patients (52.6%) in the remifentanil group; 10 of whom required a
therapeutic intervention, but in only three patients in the control group, none of whom required an intervention
(P value=0.001). Postoperative nausea and vomiting were reported in seven and 10 patients (4.7%) in the
remifentanil and control group, respectively.
These findings indicate that abdominal pain is very common in patients receiving remifentanil by infusion for
Key Words: remifentanil, side-effect, abdominal pain, cataract surgery
Remifentanil is a short-acting opioid1 which, unlike allergic reactions7; abdominal pain, however, is not
other traditional opioids, undergoes widespread mentioned as a frequent complaint in these patients.
extrahepatic metabolism, resulting in an extremely According to our experience in this field, we noted
rapid clearance in less than three to 10 minutes2-6. that a great number of patients receiving remifentanil
It is a selective µ-opioid receptor agonist that in their anaesthetic regimen experienced post-
provides rapid-onset but short-term analgesia with a operative abdominal pain. As a result, we performed
predictable duration of action with no accumulation this study to investigate its incidence.
of effect on repeated dosing or with continuous
infusion1,5. The medication is widely administered METHOD AND MATERIALS
for the induction and maintenance of anaesthesia
After obtaining approval from the ethical board
in different minor and major operations as well as in
committee of Mashhad University of Medical
a great variety of patients including children and
Sciences, this single-blinded prospective randomised
patients with renal, hepatic or cardiovascular
clinical trial was conducted on all candidates for
cataract surgery under general anaesthesia. The
Numerous studies have reported several side-
patients were selected to be in ASA class I or II;
effects for the drug including dizziness, drowsiness,
those with positive history of abdominal discomfort
nausea and vomiting, shivering, headache and
or peptic ulcer disease or opium addiction were
excluded from the study.
The patients were all informed about the
* M.D., Assistant Professor of Anesthesiology, Anesthesiology
consequences of the study and informed consent was
Department, Imam Reza Hospital, Medical Sciences/University of obtained from them. They were then divided into
† M.D., General Practitioner, Research and Development Center, Sina
two equal groups using a random allocation software.
Hospital, Medical Sciences/University of Tehran. Upon the patients’ arrival in the operating
Address for reprints: Dr P. Khashayar, Sina Hospital, Imam Khomeini St, room, standard monitoring was installed for both
Tehran 11367, Iran. remifentanil and control groups. Oxygen saturation
Accepted for publication on November 14, 2008. and ECG were monitored continuously and non-
Anaesthesia and Intensive Care, Vol. 37, No. 3, May 2009
2 S. JahanbakhSh, a. bameShki , P. KhaShayar
invasive blood pressure monitoring was performed The severity of the abdominal pain was recorded
every five minutes. After establishing venous access and scored as following: 0=no abdominal pain,
with a 20 to 22 gauge intravenous cannula and 1=mild abdominal pain reported by the patient
prior to the induction of anaesthesia, a bolus of 3 when asked about it, 2=moderate abdominal pain
to 5 ml/kg lactated Ringer’s solution followed by a reported by the patient her or himself, 3=severe
constant rate of 6 ml/kg/h was infused intravenously. abdominal pain requiring therapeutic intervention.
In the control group, anaesthesia was induced by Mild to moderate abdominal pain was managed
1 to 2 µg/kg fentanyl, 1 to 1.5 mg/kg propofol and by reassuring and informing the patients of the
0.5 mg/kg atracurium after pre-oxygenation for transient pattern of the pain; intramuscular hyoscine
three minutes; thereafter, laryngoscopy and 20 mg was injected to treat severe pain.
intubation were performed. The continuous infusion Considering the findings of the pilot study
of 50 to 150 µg/kg/min propofol and 60% N2O (a=0.05%, power=95%) 150 cases were needed for
inhalation were used to maintain anaesthesia. each group. The statistical analysis was performed
In the remifentanil group, pre-oxygenation was using SPSS version 15; t-test and chi-square were
performed prior to the induction of anaesthesia with the tests used to compare the variables. P values
2 µg/kg remifentanil, 1 to 1.5 mg/kg propofol and less than 0.05 were considered as significant.
0.5 mg/kg atracurium. The patient was then
intubated and anaesthesia was maintained by 0.3 to RESULTS
0.6 µg/kg/min remifentanil infusion and 60% N2O The 300 patients enrolled in the study were
inhalation. GlaxoSmithKline’s remifentanil was the randomly divided into two equal groups of 150
product used in the study. patients. There was no significant difference between
At the end of the surgery, the administration the demographic data including age, gender,
of anaesthetic agents was terminated without weight and haemodynamic indexes of either group
tapering. Atropine (25 to 40 µg/kg) and neostigmine (Table 1). The mean anaesthesia time in remifentanil
(50 to 80 µg/kg) were then infused to reverse the and control groups was 34.3±16.8 minutes and
muscle relaxant agents’ effects. The patients were 36.7±13.1 minutes, respectively (P value=0.168).
extubated when adequate spontaneous ventilation Postoperative nausea and vomiting was observed
(VT >4 ml/kg) was established. in seven cases (4.7%) in the remifentanil group
The patients were directly transferred to the post- and 10 cases (6.7%) in the control group; however,
anaesthesia care unit where monitoring including no statistically significant difference was reported
pulse oximetry, ECG monitoring and NIbP between the two groups (P=0.454).
measurement was continued. The minimum stay in Abdominal pain during the postoperative
the postoperative care unit was 30 minutes and the period was observed in 79 patients (52.6%) of the
patients were transferred to the ward when they remifentanil group and three cases (2%) of
were haemodynamically stable. the control group. The incidence of abdominal pain
A technician, unaware of the objectives of the in the remifentanil group was significantly higher
study, was responsible for monitoring the patients than the control group (P value=0.001). Severe
in the postoperative care unit for the presence of abdominal pain requiring intervention was
symptoms such as abdominal pain, nausea and reported in 10 patients (6.7%) in the remifentanil
vomiting. group, whereas neither of the control cases reported
Comparison of demographic characteristics of haemodynamic indexes in remifentanil and control groups
Variable Remifentanil Group (n=150) Control Group (n=150) P value
Gender (M/F) 86/64 79/71 0.1550
Age (y) 68.3±12.6 (43-87) 66.3±11.1 (40-78) 0.1505
Weight (kg) 62.7±9.8 (51-95) 64.2±11.2 (50-95) 0.2157
Systolic bP (mmHg) 152±18.4 (114-180) 137±20.2 (110-176) 0.3658
Diastolic bP (mmHg) 87±12.1 (53-96) 89±11.3 (60-102) 0.1401
Mean arterial bP (mmHg) 106±15.4 (83-138) 109±17.5 (80-141) 0.1160
Heart rate (beat/min) 98±13.4 (71-121) 95±16.3 (66-110) 0.0827
Anaesthesia and Intensive Care, Vol. 37, No. 3, May 2009
CaSe reporT 3
such a pain (Table 2). The pain was relieved investigations, however, are required to determine the
following the administration of the abovementioned exact aetiology of remifentanil-induced abdominal
medication in both groups. pain, its prevalence and management.
Comparison of incidence and severity of abdominal pain in
remifentanil and control groups According to the findings of the present study,
abdominal pain is a prevalent side-effect in patients
Mild Moderate Severe Total receiving remifentanil; the cause, however, needs
Remifentanil 43 (54.4%) 26 (32.9%) 10 (12.7%) 79 (52.6%) further studies. It is recommended to compare the
Control 2 (66.7%) 1 (33.3%) 0 (0.0%) 3 (2%) effects of different analgesic agents in the future
studies conducted on a larger sample size in order
to reveal the underlying mechanism contributing to
DISCUSSION this pain.
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Anaesthesia and Intensive Care, Vol. 37, No. 3, May 2009