Anaesthesia and Intensive Care, Vol. 37, No. 3, May 2009

Remifentanil is a short-acting opioid1 which, unlike other traditional opioids, undergoes widespread extrahepatic metabolism, resulting in an extremely rapid clearance in less than three to 10 minutes2-6.

It is a selective µ-opioid receptor agonist that provides rapid-onset but short-term analgesia with a predictable duration of action with no accumulation of effect on repeated dosing or with continuous infusion1,5. The medication is widely administered for the induction and maintenance of anaesthesia in different minor and major operations as well as in a great variety of patients including children and patients with renal, hepatic or cardiovascular diseases1,6.

Numerous studies have reported several side-effects for the drug including dizziness, drowsiness, nausea and vomiting, shivering, headache and

allergic reactions7; abdominal pain, however, is not mentioned as a frequent complaint in these patients. According to our experience in this field, we noted that a great number of patients receiving remifentanil in their anaesthetic regimen experienced post-operative abdominal pain. As a result, we performed this study to investigate its incidence.

METHOD AND MATERIALSAfter obtaining approval from the ethical board

committee of Mashhad University of Medical Sciences, this single-blinded prospective randomised clinical trial was conducted on all candidates for cataract surgery under general anaesthesia. The patients were selected to be in ASA class I or II; those with positive history of abdominal discomfort or peptic ulcer disease or opium addiction were excluded from the study.

The patients were all informed about the consequences of the study and informed consent was obtained from them. They were then divided into two equal groups using a random allocation software.

Upon the patients’ arrival in the operating room, standard monitoring was installed for both remifentanil and control groups. Oxygen saturation and ECG were monitored continuously and non-

* M.D., Assistant Professor of Anesthesiology, Anesthesiology Department, Imam Reza Hospital, Medical Sciences/University of Mashhad.

† M.D., General Practitioner, Research and Development Center, Sina Hospital, Medical Sciences/University of Tehran.

Address for reprints: Dr P. Khashayar, Sina Hospital, Imam Khomeini St, Tehran 11367, Iran.

Accepted for publication on November 14, 2008.

Remifentanil-induced abdominal pain: a randomised clinical trialS. JAHANbAKHSH*, A. bAMESHKI*, P. KHASHAyAR†Anesthesiology Department, Imam Reza Hospital, Tehran, Iran

SUMMARyRemifentanil 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 cataract surgery.

Key Words: remifentanil, side-effect, abdominal pain, cataract surgery

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2 S. JahanbakhSh, a. bameShki , P. KhaShayar

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invasive blood pressure monitoring was performed every five minutes. After establishing venous access with a 20 to 22 gauge intravenous cannula and prior to the induction of anaesthesia, a bolus of 3 to 5 ml/kg lactated Ringer’s solution followed by a constant rate of 6 ml/kg/h was infused intravenously.

In the control group, anaesthesia was induced by 1 to 2 µg/kg fentanyl, 1 to 1.5 mg/kg propofol and 0.5 mg/kg atracurium after pre-oxygenation for three minutes; thereafter, laryngoscopy and intubation were performed. The continuous infusion of 50 to 150 µg/kg/min propofol and 60% N2O inhalation were used to maintain anaesthesia.

In the remifentanil group, pre-oxygenation was performed prior to the induction of anaesthesia with 2 µg/kg remifentanil, 1 to 1.5 mg/kg propofol and 0.5 mg/kg atracurium. The patient was then intubated and anaesthesia was maintained by 0.3 to 0.6 µg/kg/min remifentanil infusion and 60% N2O inhalation. GlaxoSmithKline’s remifentanil was the product used in the study.

At the end of the surgery, the administration of anaesthetic agents was terminated without tapering. Atropine (25 to 40 µg/kg) and neostigmine (50 to 80 µg/kg) were then infused to reverse the muscle relaxant agents’ effects. The patients were extubated when adequate spontaneous ventilation (VT >4 ml/kg) was established.

The patients were directly transferred to the post-anaesthesia care unit where monitoring including pulse oximetry, ECG monitoring and NIbP measurement was continued. The minimum stay in the postoperative care unit was 30 minutes and the patients were transferred to the ward when they were haemodynamically stable.

A technician, unaware of the objectives of the study, was responsible for monitoring the patients in the postoperative care unit for the presence of symptoms such as abdominal pain, nausea and vomiting.

The severity of the abdominal pain was recorded and scored as following: 0=no abdominal pain, 1=mild abdominal pain reported by the patient when asked about it, 2=moderate abdominal pain reported by the patient her or himself, 3=severe abdominal pain requiring therapeutic intervention.

Mild to moderate abdominal pain was managed by reassuring and informing the patients of the transient pattern of the pain; intramuscular hyoscine 20 mg was injected to treat severe pain.

Considering the findings of the pilot study (a=0.05%, power=95%) 150 cases were needed for each group. The statistical analysis was performed using SPSS version 15; t-test and chi-square were the tests used to compare the variables. P values less than 0.05 were considered as significant.

RESULTSThe 300 patients enrolled in the study were

randomly divided into two equal groups of 150 patients. There was no significant difference between the demographic data including age, gender, weight and haemodynamic indexes of either group (Table 1). The mean anaesthesia time in remifentanil and control groups was 34.3±16.8 minutes and 36.7±13.1 minutes, respectively (P value=0.168).

Postoperative nausea and vomiting was observed in seven cases (4.7%) in the remifentanil group and 10 cases (6.7%) in the control group; however, no statistically significant difference was reported between the two groups (P=0.454).

Abdominal pain during the postoperative period was observed in 79 patients (52.6%) of the remifentanil group and three cases (2%) of the control group. The incidence of abdominal pain in the remifentanil group was significantly higher than the control group (P value=0.001). Severe abdominal pain requiring intervention was reported in 10 patients (6.7%) in the remifentanil group, whereas neither of the control cases reported

Table 1Comparison 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

Mean±SD (min-max).

3CaSe reporT

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such a pain (Table 2). The pain was relieved following the administration of the abovementioned medication in both groups.

DISCUSSIONOpioids are among routine anaesthetic agents

used in almost all anaesthetic regimens. They provide perfect intra- and postoperative analgesia as well as better control of haemodynamic changes; however, several side-effects including respiratory depression, ileus and postoperative nausea and vomiting are commonly reported following the use of these agents8,9.

Abdominal pain was the most frequent complaint reported in the remifentanil group of our study. In view of our previous experiences, this side-effect commonly considered as incisional site pain is frequently reported in patients undergoing abdominal surgery; however, it is masked by the administration of analgesics in the postoperative period. As a result, we studied patients under-going a cataract surgery which is a minor, less invasive surgery, so that they wouldn’t need any supplementary analgesics for alleviating the severe surgical site pain.

The mechanism of abdominal pain after anaesthesia using remifentanil is unknown, though several reports have noted postoperative remifentanil-induced hyperalgesia in animal models and humans which is believed to be controlled by adding low doses of ketamine to the anaesthetic regimen7,10,11.

In opposition, the present study reports obvious visceral and obscure abdominal pain, different from remifentanil-induced hyperalgesia. However, considering the fact that the pain was alleviated with hyoscine, an antispasmodic, it is possible that postoperative spasm in bowel smooth muscles has contributed to the high number of abdominal complaints following the use of the drug. Further

investigations, however, are required to determine the exact aetiology of remifentanil-induced abdominal pain, its prevalence and management.

CONCLUSIONAccording to the findings of the present study,

abdominal pain is a prevalent side-effect in patients receiving remifentanil; the cause, however, needs further studies. It is recommended to compare the effects of different analgesic agents in the future studies conducted on a larger sample size in order to reveal the underlying mechanism contributing to this pain.

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Table 2Comparison of incidence and severity of abdominal pain in

remifentanil and control groups

Mild Moderate Severe Total

Remifentanil 43 (54.4%) 26 (32.9%) 10 (12.7%) 79 (52.6%)

Control 2 (66.7%) 1 (33.3%) 0 (0.0%) 3 (2%)