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Keywords:

  • Bupivacaine;
  • laparoscopy and dye;
  • postoperative pain

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The aim of this randomised, double-blind, placebo-controlled trial was to evaluate the effectiveness of intraperitoneal instillation of bupivacaine following laparoscopy and dye test. Women received either 15 ml of 0.9% saline (n= 42) or 15 ml of 0.5% bupivacaine (n= 43), which was instilled intraperitoneally. Pain and nausea scores were recorded on a visual analogue scale (VAS). Pain perception was no different in the bupivacaine group compared with the control group with median values of VAS at 2 hours (18, 19; P= 0.8), 6 hours (21, 22; P= 0.5), 12 hours (19, 25; P= 0.8), 24 hours (27, 27; P= 0.9) and 48 hours (21, 13; P= 0.26). Women in the bupivacaine group were less nauseated than controls in the immediate postoperative period (with median VAS scores of 0, 8; P value = 0.03 at 2 hours and 0, 7; P= 0.01 at 6 hours).


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Assessment of the female pelvis and confirmation of tubal patency by laparoscopy and dye (L & D) is a helpful step in the diagnosis and management of infertility. Laparoscopy is generally performed as a day-case procedure, but it can be associated with postoperative pain and vomiting that can lead to overnight hospital stay. A systematic review of randomised controlled trials1 has confirmed the beneficial impact of intraperitoneal (IP) use of local anaesthetic agents in a number of laparoscopic procedures including cholecystectomy. The use of intraoperative local anaesthetic agents to reduce postoperative pain following day-case laparoscopy has several advantages over other drugs like opiods in terms of adverse effects such as postoperative nausea, sedation, delayed return of gastrointestinal motility and pruritus.

Previous studies2,3 have suggested that local anaesthetic agents instilled intraperitoneally or injected locally at the port sites may reduce early postoperative pain (6–8 hours) in women undergoing laparoscopic sterilisation. IP instillation of 0.25% bupivacaine has also been shown to be effective for pain relief in women undergoing diagnostic laparoscopy without tubal patency testing.4 To our knowledge, there are no randomised controlled trials which have evaluated the effectiveness of IP local anaesthetic agents in reducing postoperative pain following ‘L & D test’ procedures under general anaesthesia.

It is believed that postoperative pain following diagnostic laparoscopy is caused by peritoneal stretching, diaphragmatic irritation by carbon dioxide (CO2) used to create a pneumoperitoneum and, to a lesser extent, the incision at the site of abdominal puncture. Concomitant chromotubation causes distension and stretching of the tubes. IP instillation of local anaesthetic agents could potentially offer a useful method of early postoperative pain relief. Bupivacaine has an advantage over other local anaesthetic agents in this context, due to its prolonged duration of action. The aim of this trial was to evaluate the effect of IP bupivacaine irrigation on postoperative pain following L & D.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

A double-blind randomised controlled trial was conducted. The primary outcome was pain score measured on a 100-mm visual analogue scale (VAS), where ‘0 mm’ represented ‘no pain’ and ‘100 mm’ represented ‘worst pain’. The sample size calculation in this trial was identical to one used in a previous trial on ropivacaine instillation following laparoscopic sterilisation3 where pain scores were assessed by a similar VAS. Assuming a SD of 17 mm, a total of 74 women were required (37 in each group) in order to provide 80% power at the 5% level of significance in terms of detecting a difference of 13-mm difference in pain scores on a 100-mm VAS. Allowing for a 10% loss to follow up, we aimed to recruit 85 women. Ethics approval was obtained from the Grampian Research Ethics Committee. Women listed for diagnostic L & D test as a part of their fertility investigations from September 2002 to May 2005 were invited to participate in the trial. Women with a known allergy to amide local anaesthetic agents were excluded as were those with a history of alcohol or drug abuse or major psychiatric illness. Written consent was obtained from all participants. Laparoscopy was performed using standard techniques, i.e. double puncture using approximately 3 l of CO2 for insufflation in order to maintain the intra-abdominal pressure at 20–25 mmHg. Tubal patency was checked by injecting the contents of a 20-ml syringe containing methylene blue dye diluted with saline (1 ml of methylene blue diluted in 500 ml of saline) through the cervix. A standard protocol for the anaesthetic and postoperative analgesia was followed in all cases. None of the women was provided with patient-controlled analgesia pumps. After discharge from hospital, women had the option of using varying doses of oral postoperative analgesic agents provided to them on the day-case ward.

The patient, surgeon and ward nurses were blinded to the assigned treatment. Participating women were randomised at the time of surgery using a computer-generated random number to receive sodium chloride. Randomisation was performed in theatre, by a theatre assistant, by opening consecutively numbered, sealed, opaque envelopes. At the end of the surgical procedure, 15 ml of either 0.5% bupivacaine (75 mg) or 0.9% saline (both clear colourless solutions) was drawn up in identical unlabelled syringes by the theatre assistant and handed to the surgeon who instilled the entire contents of the syringe into the pouch of Douglas through a 5-mm side port. The dose of bupivacaine used in the trial was determined by considerations of safety and practicality. The maximum recommended dose of bupivacaine is 2 mg/kg body weight. As part of the normal protocol, 5 ml of 0.25% lignocaine was injected at the port sites in all women. It was therefore felt that higher doses of bupivacaine could compromise safety due to the additive effects of the two local anaesthetic agents. Plasma levels of bupivacaine were not recorded. Duration of surgery was not recorded, although all cases were completed within the limits for day-case surgery.

Preoperatively each woman was instructed to complete, within 48 hours of surgery, a questionnaire on postoperative pain and symptoms of nausea/vomiting (PONV). Women used 100-mm VASs to record the severity of both pain and nausea/vomiting at specific time intervals for up to 48 hours. Women were also asked to record their analgesic and antiemetic requirements after discharge from hospital and before mailing back completed questionnaires. Data were entered into a personal computer using SPSS for windows (version 13; SPSS Inc., Chicago, IL, USA) by one the researchers (S.S.) who was blinded to the drug used. At completion of the study, the randomisation code was broken and pain perception, PONV, analgesic and antiemetic requirements were compared between the study and control groups. Analysis was performed by intention to treat. The Mann–Whitney U test was used to compare pain and nausea scores, while the chi-square statistic was used to compare the differences in proportion of women requiring analgesics and antiemetics postoperatively.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Of 90 eligible women, 5 declined to participate. Eighty-five consecutive women undergoing L & D, as day cases were randomised to receive either bupivacaine or normal saline (Figure 1). There were no intraoperative surgical or anaesthetic complications in either group. Of the 43 women allocated to bupivacaine, 3 did not receive the drug as the surgeon forgot to administer it and one procedure was cancelled. Of the 42 women allocated to saline, 2 did not receive the drug as the surgeon forgot to administer the drug, and in 1 case the randomisation code was lost. The baseline characteristics, including age, body mass index, duration of infertility and factor causing infertility, of the cases and controls were comparable. Bilateral tubal blockage was found in three women in the bupivacaine group and in one woman in the saline group. Five women in the treatment group and two women in the control group did not return the questionnaire.

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Figure 1. Flow diagram of patients in the trial.

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Immediate postoperative nausea and vomiting (as recorded on a VAS) was lower in the bupivacaine group (P= 0.03). Perception of pain at various points in time within 48 hours after the operation was similar in the two randomised groups (Table 1). Frequency of use of the standard postoperative analgesics was not significantly different in the bupivacaine group compared with the control group (26%, 40%, P= 0.21), at 6 hours (32%, 40%; P= 0.47), at 12 hours (68%, 81%; P= 0.19) or at 24 hours (21%, 21%; P= 0.92), although a trend to infrequent use of analgesics was identified in the bupivacaine group. Lower pain scores (VAS ≤ 2.2 mm) was found at 6 hours and higher pain scores (VAS > 2.2 mm) was noted at 24 hours in both the saline and bupivacaine groups. One woman required overnight stay. There were no intraoperative or postoperative complications and operative findings are recorded in Table 1.

Table 1.  Comparison of pain, nausea and operative findings
 Bupivacaine, n= 43Saline, n= 42Difference between medians (95% CI)P value
Median VAS score in mm (IQR)Median VAS score in mm (IQR)Mann–Whitney U test
  1. IQR, interquartile range.

Postoperative pain at (hours)
 219 (8–35)18 (7–44)10 (−9 to 8)0.80
 622 (6–35)21 (9–49)1 (−13 to 0)0.55
1225 (15–47)19 (11–59)6 (−10 to 10)0.75
2427 (15–47)27 (9–53)−0.5 (12 to 10)0.99
4813 (7–25)21 (6–47)−5 (−16 to 3)0.26
Postoperative nausea at (hours)
 20 (0–10)8 (0–45)−2 (−15 to 0)0.03
 60 (0–3)7 (0–20)−3 (−10 to 0)0.01
120 (0–3)0 (0–1)0 (−2 to 0)0.17
240 (0–2)0 (0–2)00.29
480 (0–2)0 (0–1)00.62
Postoperative analgesic intake (hours), n (%)Relative risk (95% CI)Chi-square test
 29/34 (26)15/37 (40)0.65 (0.33–1.30)0.21
 611/34 (32)15/37 (40)0.79 (0.43–1.49)0.47
1223/34 (68)30/37 (81)0.83 (0.63–1.10)0.19
247/34 (21)8/37 (21)0.95 (0.39–2.30)0.92
Postoperative antiemetic intake (hours), n (%)Relative risk (95% CI)Chi-square test
 23/34 (8)6/37 (16)0.54 (0.15–2.0)0.35
 61/34 (2)5/37 (13)0.22 (0.03–1.78)0.11
122/34 (5)2/37 (5)1.08 (0.16–7.13)0.93
Operative findings and cointerventions, n (%)Chi-square test
Adhesiolysis0 (0)1 (2.3) 0.57
Tubal blockage12 (27.9)7 (16.6) 0.33
Cyst aspiration0 (0)1 (2.4) 0.57
Hysteroscopy2 (4.6)0 (0) 0.57
Endometriosis5 (11.6)8 (19) 0.57

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The results of this trial indicate that IP instillation of bupivacaine in the dose described above during L & D offers no advantages in terms of postoperative pain. Use of bupivacaine does, however, reduce the severity of postoperative nausea and vomiting.

To our knowledge, this is the first double-blind randomised trial to evaluate the use of IP bupivacaine in women undergoing L & D tests under general anaesthesia. A potential weakness of this trial is that the operation was carried out by a number of surgeons. These procedures are performed on a generic day-case theatre list that is staffed by a complement of 3–4 surgeons by rotation. Thus, allocating a single surgeon to perform all the procedures was not feasible in our trial and we used a standard operating technique to ensure uniformity. We feel that this pragmatic approach is likely to increase the generalisability of the findings. As shown in Table 1, the differences in intraoperative findings between treatment and control groups were not significant, although the numbers were small. Evidently it was impossible to control for such factors in such a study.

A randomised trial5 on women undergoing hysterosalpingograms did not show any benefits associated with intrauterine lignocaine administration. In a study on infertile women who underwent microlaparoscopy under local anaesthesia and conscious sedation, subdiaphragmatic IP instillation of 40 ml of 0.5% bupivacaine (200 mg) was found to reduce the incidence of postoperative pain and the subsequent use of analgesics.6 Other studies involving the IP instillation of local anaesthetic agents2,3 in the management of postoperative pain following laparoscopic sterilisation were able to demonstrate the analgesic effects of IP bupivacaine with much larger doses of local anaesthetic agents (200–285 mg).

In contrast to the above, women in this trial received a smaller dose (75 mg) of bupivacaine that was not titrated to body weight. This dose underwent further dilution with the volume of dye injected (average of 20 ml) into the pouch of Douglas. Thus, it is difficult to rule out the possibility that the lack of any difference in pain scores between experimental and control groups could be dose related. At the same time, it is important to point out that as pain scores were low in both groups (maximum median score = 2.7 mm), any advantage that may accrue from very high doses of bupivacaine may be minimal and needs to be balanced against the risk of toxicity.

Pain from L & D may result from a number of factors including the skin incision, stretching of the peritoneum and additionally distension of the uterus and fallopian tubes. Pain scores in both groups were low in the early postoperative period (1.9 mm) and were higher at 24 hours (2.7 mm). This may be related to the cessation of the effect of the lignocaine that was infiltrated subcutaneously at the site of the laparoscopy ports.

Women who received bupivacaine reported less nausea and vomiting. The median difference in nausea scores (Table 1) is the median of all pairwise differences between observations in drug group minus each observation in saline group. The calculation of the CI assumes that the two groups have the same population distribution function apart from a possible difference in location parameters and is based on an approximation.7 This explains why the CI contains zero while the Mann–Whitney P value is significant. We believe that this may be due to the suppression of vagal and splanchnic afferents arising from bowel stimulation as a result of mechanical traction, manipulation and displacement, by the action of the local anaesthetic agents.8

It is likely that women with tubal blockage undergoing L & D may experience more pain when dye is forced through. However, there was no significant difference between the groups in the frequency of tubal blockage. Any future studies investigating women undergoing L & D may need to use larger doses of local anaesthetic agents to account for dilutional effects of the dye injected.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

IP instillation of 75 mg of bupivacaine at the end of L & D test does not alter the intensity of pain following the procedure or analgesic requirement, but it reduces the intensity of postoperative nausea and vomiting.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References
  • 1
    Moiniche S, Jorgensen H, Wetterslev J, Dahl JB. Local anesthetic infiltration for postoperative pain relief after laparoscopy: a qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block. Anesth Analg 2000;90:899912.
  • 2
    Benhamou D, Narchi P, Mazoit JX, Fernandez H. Postoperative pain after local anesthetics for laparoscopic sterilization. Obstet Gynecol 1994;84:87780.
  • 3
    Callesen T, Hjort D, Mogensen T, Schouenborg L, Nielsen D, Reventlid H, et al. Combined field block and i.p. instillation of ropivacaine for pain management after laparoscopic sterilization. Br J Anaesth 1999;82:58690.
  • 4
    Loughney AD, Sarma V, Ryall EA. Intraperitoneal bupivacaine for the relief of pain following day case laparoscopy. Br J Obstet Gynaecol 1994;101:44951.
  • 5
    Frishman GN, Spencer PK, Weitzen S, Plosker S, Shafi F. The use of intrauterine lidocaine to minimize pain during hysterosalpingography: a randomized trial. Obstet Gynecol 2004;103:12616.
  • 6
    Pellicano M, Zullo F, Di Carlo C, Zupi E, Nappi C. Postoperative pain control after microlaparoscopy in patients with infertility: a prospective randomized study. Fertil Steril 1998;70:28992.
  • 7
    McKean JW, Ryan TA Jr. An algorithm for obtaining confidence intervals and point estimates based on ranks in the two sample location problem. ACM Trans Math Software 1977;3:1835.
  • 8
    Lerman J. Surgical and patient factors involved in postoperative nausea and vomiting. Br J Anaesth 1992;69(7 Suppl 1):24S32S.