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Original Article

Randomized controlled trial investigating the effect of transcervical papaverine and bupivacaine on postoperative analgesia following laparoscopic sterilization

Ng, A.*; Habib, A.*; Swami, A.*; Smith, G.*; Nunns, D.; Davidson, A. C.

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European Journal of Anaesthesiology (EJA): November 2002 - Volume 19 - Issue 11 - p 803-807
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A critical factor that delays discharge and leads to hospital admission is pain after day case surgery [1]. Laparoscopic sterilization is a common procedure and in comparison with diagnostic gynaecological laparoscopy, it is believed that tight clips or rings applied to Fallopian tubes cause additional pain [2] induced by ischaemia or spasm [3]. Therefore, drugs with local anaesthetic or muscle relaxant properties may be useful: the former in blocking neural conduction and the latter in reducing tubular spasm.

Papaverine is a smooth muscle relaxant that acts via phosphodiesterase inhibition [4]. It is instilled commonly into the male genital system for treatment of impotence. It has been used for cerebral vasospasm following subarachnoid haemorrhage, intermittent claudication and visceral spasm. The aim was to evaluate if transcervical papaverine would reduce abdominal pain after laparoscopic sterilization and to compare this effect with those of transcervical bupivacaine and normal saline.


After obtaining local Institutional Ethics Committee approval, we studied 66 females of ASA Grades I-II undergoing laparoscopic sterilization. After signed informed consent had been obtained from the patients, they were allocated randomly to one of three treatment groups: bupivacaine, papaverine and placebo (Fig. 1). These groups were determined by computerized random number generation in blocks of six. Pain assessments and the provision of postoperative rescue analgesia were explained preoperatively.

Figure 1
Figure 1:
Enrolment, intervention allocation, follow-up and data analysis.

Exclusion criteria included known allergies to bupivacaine and papaverine, diagnosed chronic pain syndrome, pelvic inflammatory disease, pelvic adhesions and a history of regular analgesic ingestion. In addition, patients were excluded if they were unsuitable for a laryngeal mask airway or the use of diclofenac suppositories, and if they could not comply with the pain assessment used postoperatively. Exclusions concerning surgery were operative difficulties such as incorrect insufflation, conversion to an open procedure, use of more than one clip to one Fallopian tube and the application of the clip on the lateral two-thirds of the Fallopian tube.

All patients were given a standard general anaesthetic, comprising propofol 2-4 mg kg−1, fentanyl 1 μg kg−1 and a muscle relaxant at induction of anaesthesia. Patients' lungs were ventilated to normocapnia with nitrous oxide and isoflurane in oxygen via a standard laryngeal mask airway. Suppositories of diclofenac 100 mg and intravenous (i.v.) ondansetron 4 mg were given to all patients at the beginning of surgery. Residual neuromuscular block was antagonized with neostigmine 2.5 mg with glycopyrrolate 500 μg. In the postoperative period, rescue analgesia comprised oral codeine 60 mg with oral paracetamol 1 g, and intramuscular morphine 10 mg if necessary. An independent person prepared the appropriate solution from instructions in the sealed randomized envelopes; these comprised saline 0.9% 30 mL, bupivacaine 0.375% 30 mL and papaverine 30 mg in saline 0.9% 30mL.

Of the appropriate solution, 30 mL was carefully injected through a Spackman's cannula placed into the cervix of the uterus before the Filshie clips were applied. The syringe was left at the end of the cannula to prevent reverse flow of drug out of the cannula. A Filshie clip was applied to the medial one-third of each Fallopian tube. Manipulation of the uterus during sterilization was carried out using the Spackman's cannula. Records were made of the time of drug administration and any difficulties during the procedure.

In the postoperative period, visual analogue pain scores were recorded at rest on a scale of 0 (no pain) to 100 mm (worst imaginable pain). Assessments were made on awaking, 30 min later and then at 1, 2, 3 and 4 h after operation by an observer blinded to the patient group. Time to any rescue analgesia was recorded. In addition, side-effects such as hypotension, nausea and vomiting were recorded. At the same time intervals, suitability for discharge was assessed using our hospital's day-surgery unit guidelines.

From a previous study [5] on the efficacy of local anaesthetics administered to patients undergoing laparoscopic sterilization, it was estimated that 21 patients per group were needed for a 90% chance of detecting a 40% reduction in the proportion of patients requesting rescue analgesia within the first postoperative hour. Data were analysed by study of variance and Kruskal-Wallis tests for normally and non-normally distributed data respectively. Kaplan-Meier survival analysis analysed data of the time to first analgesia and a log rank test tested for statistical significance of the graphical data.


Of the 66 patients recruited into the trial, three did not complete the study. One patient in the saline group had prolonged apnoea to mivacurium requiring admission to the intensive care unit. On further investigation, she had plasma cholinesterase deficiency. Another patient in the same group changed her mind and declined to participate in the study. One patient in the bupivacaine group was excluded because of a retroverted uterus that did not allow transcervical administration.

The three groups were similar in physical characteristics. There were no significant differences in mean age and median body mass index (BMI) between the three groups.

There were no significant differences in the median visual analogue pain scores between the three groups at all times in the postoperative period (Table 1). The time to first analgesia and median survival times did not differ significantly between the three groups (Fig. 2 and Table 2).

Table 1
Table 1:
Visual analogue pain scores (mm).
Figure 2
Figure 2:
Time to first analgesia in the postoperative period (Kaplan-Meier survival analysis). ―――: Placebo; ······: papaverine; ―: bupivacaine.
Table 2
Table 2:
Time to first administration of analgesia (min).

Analgesic consumption did not differ significantly between the three groups in terms of the number of patients in each group: who did not require analgesia; who had codeine 60 mg with paracetamol 1 g only; morphine only; or the combination of codeine 60 mg with paracetamol 1 g and morphine (Table 3). In addition, the number of patients in each group receiving analgesia within the first postoperative hour did not differ significantly.

Table 3
Table 3:
Analgesic consumption.

The combined incidence rate of postoperative nausea and vomiting was 19%. There was no significant difference between the groups in postoperative nausea and vomiting or requirement for additional antiemetics (Table 4). Sedation scores were low and did not differ significantly between groups. In addition, no adverse effects of bupivacaine or papaverine, e.g. hypotension, were detected.

Table 4
Table 4:
Antiemetic consumption, postoperative nausea and vomiting.


It was found that neither intrauterine papaverine nor intrauterine bupivacaine improved analgesia with rectal diclofenac 100 mg following laparoscopic sterilization with Filshie clips. Papaverine is effective for treating conditions in which there is muscular spasm, and bupivacaine is effective in blocking neural conduction. It may be that our failure to demonstrate a significant analgesic effect arises in the method of administration. Although transcervical administration allows drugs to be targeted directly to the site of application of the clips, there may be substantial loss into the peritoneal cavity via the lateral ends of the Fallopian tubes, despite careful, slow administration. A more viscous preparation such as a gel with the same dose of drug may possibly be effective and this warrants further evaluation.

The dose of bupivacaine and papaverine should have been sufficient to produce analgesia. In a study similar to the present one, a slightly higher dose of bupivacaine 0.25% 50 mL was associated with a reduction in the consumption of analgesic drugs postoperatively [6]. However, very high doses of bupivacaine would increase the risk of toxicity.

Clinical studies concerning the use of antispasmodic and local anaesthetic drugs in the treatment of pain after laparoscopic sterilization have demonstrated variable success. Previous prospective double-blind placebo-controlled randomized clinical trials have shown that pain may be reduced with glycopyrrolate 0.3 mg i.v. given before induction of anaesthesia [7] but not with i.v. buscopan [8,9]. Application of lidocaine gel 2% to Filshie clips was ineffective in one trial [10] but beneficial in another [5]. Lidocaine 1% given intermittently via a catheter placed intraoperatively into the Pouch of Douglas [11] or lidocaine 1% administered into the subserosal aspect of the cornual end of the Fallopian tubes [12] has been shown to reduce pain intensity after laparoscopic sterilization. Bupivacaine 0.5% applied topically to each Fallopian tube under direct vision relieves the intensity of pain after operation and increases the time to first analgesia [13]. In addition, intraoperative application of bupivacaine 0.5% to the mesosalpinx via a long suprapublic needle has produced similar benefits [14,15].

In conclusion, we found that papaverine 30 mg or bupivacaine 0.375% 30 mL administered into the uterine cavity and Fallopian tubes via the transcervical route did not provide additional analgesic effects following laparoscopic sterilization. Consequently, we do not recommend their routine administration.


The work was presented, in part, at the meeting of the Anaesthetic Research Society, Leeds, UK, 6 July 2001. The abstract was published in the British Journal of Anaesthesiology (Br J Anaesth 2001; 87: 663P-664P).


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© 2002 European Academy of Anaesthesiology