Intraperitoneal Ropivacaine and a Gas Drain: Effects on Postoperative Pain in Laparoscopic Surgery

Ropivacaine and Gas Drain in Operative Laparoscopy Readman et al

Intraperitoneal Ropivacaine and a Gas Drain: Effects on Postoperative Pain in Laparoscopic Surgery Emma Readman, M.B., B.S., Peter J. Maher, M.B., B.S., FRANZCOG, Antony M. Ugoni, B. Sci. (hons), M. Sci., and Simon Gordon, M.B., B.S., FRANZCOG Abstract

(J Am Assoc Gynecol Laparosc 2004, 11(4):486–491)

Study Objective. To assess the benefits of the combination of a gas drain and the instillation of local anesthetic on the incidence of pain after operative gynecologic laparoscopy. Design. Randomized control trial (Canadian Task Force classification I). Setting. Tertiary referral center. Patients. One hundred twenty-eight patients undergoing operative gynecologic laparoscopy procedures lasting less than 105 minutes. Interventions. Postoperatively, one group received a blocked drain and saline placed intraperitoneally; a second group was given a blocked drain and ropivacaine; a third group received a patent drain and saline; and a fourth was given a patent drain and ropivacaine. Measurements and Main Results. Visual analogue pain scores (VAS) were measured at 1, 2, 4, and 12 hours and day 1 to day 7. Also measured was opioid consumption at 4 hours, nausea, and activity scores. We found a statistically significant improvement in pain scores at 2 and 4 hours in the group allocated to receive a patent drain and ropivacaine. Conclusion. We recommend the use of a gas drain and ropivacaine to reduce postoperative pain.

and a fourth group with a blocked drain and saline (control). The primary endpoints were visual analog pain scores (VAS) at 2, 4, and 12 hours postoperatively. Additional endpoints were analgesic use at 4 hours and time to recovery.

Laparoscopic postoperative pain is complex and multifactorial. The sources of pain include shoulder tip pain, operative disruption of tissues, and port site pain. There have been a number of recent studies on the use of intraperitoneal bupivacaine and ropivacaine suggesting a benefit from the instillation of either postoperatively. Ropivacaine has been shown to be more effective in reducing the need for postoperative morphine.1 Published studies show some benefit in reduction of pain from the use of a gas drain following laparoscopy.2–5 To date, there have been no trials looking at the benefit of the combination of a gas drain and the instillation of local anesthetic on the incidence of postoperative pain. The potential benefits of ameliorating multiple causes of pain, which may have a cumulative effect on pain reduction, deserve study. The object of this study was to determine whether an infusion of intraperitoneal ropivacaine (Naropin, AstraZeneca, Melbourne, Australia) combined with an intraperitoneal gas drain would reduce patient discomfort after undergoing gynecologic operative laparoscopy. It was a randomized, double-blind, controlled trial with four arms: one group of patients with an unblocked drain and ropivacaine; a second group with a blocked drain and ropivacaine; a third group with an unblocked drain and saline;

Materials and Methods This study was approved by the Mercy Hospital for Women’s Ethics Committee. Any woman who was suitable for the study was offered the chance to participate and was provided with an information sheet and a consent form preoperatively. From July 2001 through April 2002, 128 participants were recruited. Those patients with any contraindications to nonsteroidal anti-inflammatory drugs (NSAIDS) or local anesthetics were excluded. Patients with hepatic, vascular, or cardiac diseases were excluded, as were those who had undergone a hysterectomy, myomectomy, colpotomy, or any other concomitant nonendoscopic procedure in the course of the operation. Anyone not speaking enough English to complete the questionnaires was not invited to participate. The surgery was performed at the Mercy Hospital for Women, by one of three of the authors (PJM, SG, ER).

From the Department of Endosurgery, Mercy Hospital for Women, East Melbourne (Drs. Readman, Maher, and Gordon), and School of Physiotherapy, University of Melbourne (Mr. Ugoni), Victoria, Australia. Corresponding author Emma Readman, M.B., B.S., Endosurgery Unit, Mercy Hospital for Women, Clarendon Street, East Melbourne, 3002 Victoria, Australia. Submitted July 21, 2003. Accepted for publication June 14, 2004. Reprinted from the JOURNAL OF THE AMERICAN ASSOCIATION OF GYNECOLOGIC LAPAROSCOPISTS, November 2004, Vol. 11 No. 4 © 2004 The American Association of Gynecologic Laparoscopists. All rights reserved. This work may not be reproduced in any form or by any means without written permission from the AAGL. This includes but is not limited to, the posting of electronic files on the Internet, transferring electronic files to other persons, distributing printed output, and photocopying. To order multiple reprints of an individual article or request authorization to make photocopies, please contact the AAGL.

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Basic demographic data including age, weight, and operative time and complexity were recorded. The operative procedures were laparoscopic removal of endometriosis and division of adhesions. The operative complexity was graded minimal, mild, moderate, or severe, based on the amount of peritoneum that was excised. Minimal was a few spots; mild was 2 or 3 areas greater than 1 cm but superficial; moderate was any areas that were more than superficial but not distorting the pelvis; and severe was obliterative disease. A standard analgesia protocol was followed. The premedication was 100 mg of rectal diclofenac, followed by propofol induction and anesthetic maintenance using an air, oxygen, and sevoflurane mixture. The muscle relaxant was atracurium, and reversal of anesthesia was achieved with neostigmine and atropine. All patients received 20 mg of metoclopramide, and rescue antiemetics were ondansetron 4 mg intravenously, followed by the anesthetist’s antiemetic choice. The analgesic given was 100 mcg (or 1.5 mcg/kg) of fentanyl at the time of induction. Patients entered the trial if they had an operative laparoscopic procedure lasting less than 105 minutes with no exclusion criteria and if they had agreed to participate. The time of 105 minutes was chosen because if the time was longer than 2 hours, the case was more likely to be incomparable with simpler procedures in terms of pain scores and pain relief required. Laparoscopy was performed in the standard way using four 5-mm ports. Carbon dioxide gas was the distension medium, and the intraperitoneal pressure was set at 15 mm Hg. The number 1, 2, 3, or 4 was assigned to each of the combinations of drains and instillation fluid, and a randomization program randomized them. The code was not broken until after the data were analyzed. The combined pack of instillation fluid and drain was put together by the hospital pharmacy and numbered from 1 to 128. The dose of ropivacaine was 200 mg in 100 mL of normal saline. The drain tube was a 14-gauge Indoplas (Maersk, Sydney, Australia) infant-feeding tube with a blocked end or an open end left to drain passively. At no stage was it evident whether the drains were patent, or blocked and the solutions were identical in appearance. At the conclusion of surgery, two 50 mL syringes of infusion fluid were injected by a laparoscopic cannula onto the operative sites in the pelvis, and the drain tube was inserted into one of the port sites. The patency of the tube was not obvious from external inspection. Port site closure occurred as usual. The drains were blocked for 30 minutes to allow for absorption of the ropivacaine, then unblocked externally. The blocked drain remained blocked internally. When the patient was returned to the recovery room, routine observations were taken. Fentanyl patient-controlled anesthesia (PCA) was commenced allowing the patients access to 20 mcg boluses with a 5-minute lockout time; or, if that was insufficient, the patient was given intravenous morphine or oral or intravenous tramadol. After two hours, the PCA was withdrawn, and the patient was encouraged to take paracetamol with or without codeine depending on her level of discomfort.

The nursing staff administered a VAS at 1, 2, and 4 hours after the patient’s return from the operating room. The data recorded were VAS for total pain, shoulder pain, pelvic pain, and wound pain with zero being no pain and 10 being the worst pain imaginable. The drain was removed 4 hours after the operation. The total dose of analgesia was recorded at 4 hours, as well as the presence of nausea and the drug(s) used to treat it. At discharge, the patients were handed eight VAS forms, one to be completed at 12 hours and then each day for 7 days postoperatively, and a stamped, self-addressed envelope to be returned after completion. An activity score (modified Euroquol thermometer) also was completed. Statistical Analysis The outcomes measured were the absolute change in pain scores from 1 hour (pain 1 − pain t), and the relative change in pain scores ((pain 1 − pain t)/pain 1). These measurements were described with medians, and the interquartile range was used as a measure of spread. These measurements were compared using the Kruskal-Wallis test, similarly for weight and operative time. Categorical data were compared with Fisher’s exact test. Results All patients eligible for the trial were asked to participate. Six patients declined, two because they did not like the idea of a gas drain and four because they did not want to participate for personal reasons. Of the 128 patients who were recruited, 28 patients either did not return the questionnaires or had exclusion factors, which made them ineligible for the trial. Therefore, data from 100 patients were available for analysis. All 100 patients completed the VAS so all were included in the pain score analysis, but there were incomplete data for the analgesia use at 4 hours for four patients, and two further patients required NSAIDS so they were unable to be included in the analgesia analysis, leaving data for 94 patients analyzed for analgesic requirements at 4 hours. In order to compare different opioid agents used at 4 hours, a dose equivalence chart was consulted and an overall opioid use figure calculated. On reviewing the data, at 2 and 4 hours there was a significant improvement in pain scores for the group with both patent gas drain and ropivacaine. When comparing it with the group that received ropivacaine alone, it was statistically significant. At 2 hours, there was an improvement in pelvic pain scores, both absolute and relative (Table 1, Figure 1); and at 4 hours, there was an improvement in overall pain, both absolute and relative (Table 1, Figure 2). There was also significant improvement in pelvic pain at 4 hours in the patent gas drain-alone group. There was no difference in any of the pain scores among the four groups at any other time measured. There was no difference in analgesia use at 4 hours among the different groups and no difference in time taken to full recovery. There were no side effects of the ropivacaine reported. The removal of the gas drain caused

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TABLE 1. Results at 2 and 4 Hours Absolute Overall Pain

2 hours

4 hours

Group

Median

95% CI

1 2 3 4 1 2 3 4

-0.10 0.50 0.80 0.20 -0.05 0.85 1.70 1.00

-1.00–1.01 0.07–1.27 -0.35–1.50 -0.61–0.83 -0.85–0.61 0.37–2.50 1.20–2.30 0.68–2.21

Pelvic Pain p value

.2013

.0210 1 vs 3, 1 vs 4, 1 vs 2

Median

95% CI

-0.40 0.75 1.00 0.10 0.45 1.05 1.70 1.20

-1.36–0.60 0.10–1.37 0.00–2.62 0.00–1.60 -0.20–1.06 0.50–2.63 0.18–2.75 0.29–2.40

p value

.0237 1 vs 2, 1 vs 3, 1 vs 4

.1458

Relative to 1 Hour Overall Pain

2 hours

4 hours

Pelvic Pain

Group

Median

95% CI

p value

Median

95% CI

1 2 3 4 1 2 3 4

-0.05 0.19 0.28 0.07 -0.01 0.40 0.59 0.55

-0.37–0.32 0.05–0.42 -0.11–0.60 -0.16–0.40 -0.58–0.20 0.08–0.63 0.36–0.66 0.24–0.76

0.1975

-0.16 0.40 0.47 0.18 0.27 0.52 0.50 0.73

-0.40–0.21 0.16–0.81 0.00–0.84 0.00–0.42 0.10–0.47 0.41–0.70 0.21–0.69 0.33–0.98

.0072 1 vs 2, 1 vs 3, 1 vs 4

p value .0052 1 vs 2, 1 vs 3, 1 vs 4, 2 vs 4 .0498 1 vs 2, 1 vs 4

Group 1: ropivacaine and blocked drain; Group 2: saline and blocked drain (control); Group 3: ropivacaine and patent drain; Group 4: saline and patent drain. Multiple comparisons significant at 0.05 Bonferroni level in bold. Multiple comparisons significant at 0.10 Bonferroni level in italics.

1 0.8 0.6

change in absolute pelvic pain scores, p=.0237 change in relative pelvic pain scores, p=.0052

0.4 0.2

.

0 -0.2 -0.4 Group 1 Group 2 Group 3 Group 4

FIGURE 1. Results at 2 hours. Group 1: ropivacaine and blocked drain; Group 2: saline and blocked drain (control); Group 3: ropivacaine and patent drain; Group 4: saline and patent drain. Group 3 shows the greatest reduction in pain scores comparing visual analog scale scores at 1 and 2 hours after surgery. The scores in Group 1 worsened in the same time period.

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1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 -0.2

change in absolute overall pain, p=.0210 change in relative overall pain, p=.0072

Group 1

Group 2

Group 3

Group 4

FIGURE 2. Results at 4 hours. Group 1: ropivacaine and blocked drain; Group 2: saline and blocked drain (control); Group 3: ropivacaine and patent drain; Group 4: saline and patent drain. Group 3 shows the greatest reduction in pain scores comparing visual analog pain scores at 1 and 4 hours after surgery. The scores in group 1 worsened in the same time period.

severe pain in four people. There was no difference in nausea and the number of drugs taken for nausea in each group (Table 2), nor in the patient’s weight, number of preoperative analgesics, length of operation, or complexity of operation (Table 3). There were also no statistically significant differences in pain scores for any of those subgroups shown in Table 3. There were not sufficient numbers in each to show a statistical difference, however the categories were compared to show that one group did not have a different operative profile to another group.

tion effect of the liver on the diaphragm, creating a pocket under the diaphragm and pulling on the phrenic nerve.3 Distension pressures may play a part in the etiology, causing neuropraxia from peaks in distension pressures. However, gasless laparoscopy has caused similar shoulder pain to CO2 laparoscopy, presumably from mechanical distension of the phrenic nerve and the suction effect creating pockets of room air under the diaphragm.8 Published trials of the use of an intraperitoneal gas drain after laparoscopic surgery show a spectrum of results. Three studies used a closed suction system of drainage, with a 3-mm drain tube. One of the studies found a statistically significant difference of 50% in general pain frequency at 2, 6, and 14 hours between study group and control.2 Another of the studies showed a statistically significant reduction in moderate or severe general pain by 20%–24% at 4 and 48 hours.3 The final study found statistically significant results in the reduction of shoulder tip pain at 3 days.9 Two groups used a passive drainage system. One of the studies found a statistically significant reduction in shoulder tip pain at 12, 24, 48, and 72 hours.4 The authors proposed that suction drains may be compromised by adherence of bowel or omentum to the suction holes. The other study showed a statistically significant reduction in shoulder tip pain at 4 and 48 hours, again using a passive drain, but no reduction in overall pain.5 We used a larger bore drain tube, 14 gauge, on passive drainage. Our results show that a drain tube and ropivacaine together gave better pain relief at 2 and 4 hours, with the effect presumably being attributable predominantly to the gas drain at 4 hours, since the ropivacaine-alone group did not show a positive response to pain relief. At 2 hours, the gas drain-alone group and the ropivacaine-alone group both had worse pain scores than the control group, which is difficult to explain. Perhaps there is an additive effect of

Discussion Shoulder tip pain has been attributed to the irritating effect of residual CO2 or the formation of carbonic acid.6 However, trials comparing the use of nitrous oxide and CO2 have shown no difference in pain levels.7 Another theory is that distension of the abdomen interrupts the suc-

TABLE 2. Postoperative Nausea Nausea Group

Yes

No

1 2 3 4

13 7 11 10

13 17 12 17

Group 1: ropivacaine and blocked drain; Group 2: saline and blocked drain (control); Group 3: ropivacaine and patent drain; Group 4: saline and patent drain. The incidence of nausea after the operation in each of the study groups was not statistically significant; p = .419.

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TABLE 3. Comparative Data

Weight (median, kg) Number of preoperative analgesics taken 0 1 2 3 Operative time (median, minutes) Operative complexity minimal mild moderate severe

Group 1

Group 2

Group 3

Group 4

62.5

65

65

64

19 5 1 1 51.5

18 5 0 1 58.5

23 0 0 0 52

25 0 0 2 45

11 10 4 1

13 7 4 0

8 13 1 1

9 12 5 1

Group 1: ropivacaine and blocked drain; Group 2: saline and blocked drain (control); Group 3: ropivacaine and patent drain; Group 4: saline and patent drain. This table compares the characteristics of each group in the trial. There were no statistically significant differences.

using both. It is possible that the decreased pressure in the abdomen created by the gas drain allowed for a slower absorption of ropivacaine. The fact that there was an improvement in overall and pelvic pain, but not shoulder tip pain, at 2 and 4 hours underlines the difficulty in attributing pain to a specific area, so that the patient is unable to pinpoint where the pain she feels is located, and the multifactorial nature of pain. The use of local anesthetics in laparoscopy recently has been reviewed.10 The hypothesis advanced in the use of postoperative local anesthetics is that these agents are more useful in minimally invasive procedures with reduced tissue trauma. Relevant double blind, randomized, controlled trials were analyzed, and the available trials were compared. Trials for intraperitoneal local anesthetics following laparoscopic cholecystectomy showed weak evidence for an effect on postoperative pain. Other laparoscopic procedures had a trend of decreasing pain postoperatively, although there were too many disparate procedures studied to draw any conclusions. There was a comment that more trials were needed to show an effect. The most noteworthy observation was that there was no consensus on the dose required, the site targeted, and the manner of administration. There did seem to be a clear benefit for tubal instillation of local anesthetic agent post laparoscopic sterilization. Since that review, there have been a number of studies on the gynecologic use of laparoscopic intraperitoneal local anesthetics. Four randomized controlled studies have been found. One11 compared bupivacaine, ropivacaine, and normal saline instilled postoperatively during a wide range of procedures including laparoscopic-assisted vaginal hysterectomy and myomectomy. The study found a statistically significant reduction in the need for morphine after use of either local anesthetic in the first 24 hours postoperatively.

Approximately half the local anesthetic was instilled under the diaphragm and half sprayed onto the surgical site. In preventing postoperative pain, ropivacaine (150 mg) was significantly more effective than bupivacaine (100 mg). It was noted that it would be interesting to find out if there was increasing effect at higher doses. Our group, in an earlier trial, studied patients undergoing laparoscopic excision of moderate to severe endometriosis, instilling 200 mg of ropivacaine or normal saline onto the surgical sites and found no difference in pain at 1, 3, 5, and 7 hours postoperatively or at days 1 and 7.12 Another study evaluated the effect of pre incisional (all ports) and intraperitoneal bupivacaine on immediate and late pain after operative laparoscopy and concluded that there was a statistically significant benefit not lasting more than 30 minutes postprocedure compared with saline.13 In the final study, researchers instilled 100 mg of bupivacaine in 1000 mL of Hartmann’s solution into the peritoneum at the end of the procedure. There was no difference in the pain experienced or the pain relief required at 1, 2, 6, 12, 18, and 24 hours. It was thought that the concentration of drug achieved was inadequate for pain need postoperative laparoscopy.14 Our results showed that there was no clear benefit for ropivacaine alone. It had statistically poorer scores at 2 and 4 hours compared with other groups, and at other times there was no difference among the groups. Conclusion There appears to be a clear benefit for the use of gas drains in patients undergoing laparoscopic surgery. Benefit of the use of a combination of ropivacaine and gas drain is shown, but the reason for this benefit on pain scores when the benefit of gas drain alone and ropivacaine alone is not shown is difficult to explain.

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