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© 2000 International Anesthesia Research Society
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Abstract |
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Patients undergoing laparoscopic procedures may experience postoperative pain. The intraperitoneal (IP) administration of drugs is controversial but has proven effective in some studies for the relief of postoperative pain. However, some investigators have not been able to confirm the analgesic efficacy of IP local anesthetics. The administration of IP opioids for the relief of postoperative pain has received little attention. At the end of laparoscopic tubal ligation, 100 patients received 80 mL of 0.125% bupivacaine with 1:200,000 epinephrine IP and 50 mg of meperidine either IP or IM. Postoperative pain scores were measured at rest and with movement. Pain scores were significantly lower in the group receiving the IP meperidine both at rest (P < 0.01) and with movement (P < 0.05). We conclude that the combination of intraperitoneal bupivacaine and intraperitoneal meperidine was better than the combination of IP bupivacaine and IM meperidine for postoperative analgesia in patients undergoing laparoscopic tubal ligation.
Implications: The combination of bupivacaine and meperidine delivered to the intraperitoneal cavity proved superior to equivalent doses of intraperitoneal bupivacaine and IM meperidine for postoperative pain relief in patients undergoing laparoscopic tubal ligation. Intraperitoneal delivery of analgesia proved effective in this study and merits further study and more widespread use.
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Laparoscopic surgery is associated with significantly less pain, earlier discharge from the hospital, and more rapid convalescence than equivalent procedures performed by minilaparotomy (1,2). However, patients undergoing laparoscopic procedures do experience postoperative pain, especially in the upper and lower abdomen, back, and shoulder regions (3,4). Pain after laparoscopy results from the stretching of the intraabdominal cavity (5), peritoneal inflammation (6), and phrenic nerve irritation caused by residual carbon dioxide in the peritoneal cavity (7).
Some investigators have asserted that the intraperitoneal (IP) delivery of drugs is a simple and effective method of reducing the intensity of postlaparoscopic pain (8,9). However, other investigators have not been able to confirm the analgesic efficacy of IP local anesthetics (5,10). The administration of IP opioids for the relief of postoperative pain has received little attention. Schulte-Steinberg et al. (11) reported that the IP administration of morphine failed to provide analgesia after laparoscopy. Unlike morphine, meperidine is a synthetic opioid of the phenylpiperidine series, which has local anesthetic effects both in vitro and in vivo (12,13). Armstrong et al. (13) showed that the addition of meperidine to local anesthetic for IV regional anesthesia increased the speed of onset and slowed the recovery of the blockade. IP meperidine may have the potential to provide additional analgesic benefits because of this combined opioid agonistic and local anesthetic properties.
Laparoscopic tubal ligation is a commonly performed procedure. Any interventions that ameliorate the side effects of this technique could have an impact on current clinical practice. This study was established to evaluate the effects of a combination of IP meperidine and IP bupivacaine for postoperative analgesia postlaparoscopic tubal ligation and to compare this to a combination of IP bupivacaine and IM meperidine.
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Methods |
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After informed, written consent and Irish Medicines Board and local ethical committee approval, all ASA physical status I patients undergoing laparoscopic tubal ligation were recruited in the study. Patients with hepatic, vascular, metabolic, or cardiac disease were excluded. Any patient with contraindications to meperidine or local anesthetics was also excluded, i.e., a history of anaphylactic reactions. Patients were randomized according to a table of random numbers and the results kept in, sealed envelopes that were opened at induction.
A questionnaire was completed for each patient, giving demographic, perioperative, and postoperative details. Patients were randomized according to a table of random numbers. Patients allocated to Group A received IP bupivacaine, IP saline, and meperidine while those in Group B received IP bupivacaine, IP meperidine, and IM saline.
No premedication was used. Intraoperative monitoring consisted of electrocardiogram, oxygen saturation, ET CO2, and noninvasive blood pressure. A standardized anesthetic technique was used for all patients. Anesthesia was induced with propofol (2.5–3 mg/kg) and fentanyl 2 µg/kg IV. Tracheal intubation was facilitated by atracurium 0.1 mg/kg IV, and the lungs were ventilated with intermittent positive-pressure ventilation by using a mixture of 1.5%–2% isoflurane and 66% nitrous oxide in oxygen. Ventilation was adjusted to keep ETCO2 between 30 and 40 mm Hg. No opioids were administered during the maintenance period. All patients received ondansetron 8 mg IV and diclofenac 100 mg rectally after the induction of anesthesia. Surgery was conducted in the lithotomy and Trendelenberg position. Tubal occlusion was performed with Filshie clips.
At the end of the operation, under direct vision, the patients allocated to Group A received 80 mL of 0.125% bupivacaine with 1:200,000 epinephrine, instilled into the peritoneal cavity via the umbilical port, 10 mL of saline IP and 50 mg of IM meperidine. Patients in Group B received 80 mL of 0.125% bupivacaine with 1:200,000 epinephrine and 50 mg meperidine (mixed up to 10 mL) instilled into the peritoneal cavity and 1 mL of saline IM. Carbon dioxide was then evacuated from the peritoneal cavity. The surgical wounds were not infiltrated with local anesthetic. Anesthesia was discontinued, and neuromuscular blockade was reversed with neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg at the end of surgery.
Postoperative pain was assessed both at rest and on movement (patients being asked to move from the supine to the sitting position) at 30 min and 2, 4, and 6 h postoperatively. The patients were asked to rate the severity of pain via a visual analog scale (VAS) ranging from no pain (0 cm) to worst possible pain (10 cm). The use of these measures was explained to all patients before surgery. An independent investigator blinded to the treatment group obtained the scores. No pain scores were available before surgery.
A standard postoperative analgesic regimen was used in all patients. If the VAS score was greater than 3, the patient was prescribed 0.5–1 mg/kg IM meperidine once every 4 h as required for analgesia. If the VAS score was below 3, oral acetaminophen (500 mg) once every 8 h was prescribed. The drugs were administered on demand (within the limits defined above) by an experienced recovery nurse with no knowledge of the perioperative analgesia administered. The time to the first analgesia administration and total analgesic requirements in the first 6 h was recorded. Postoperative nausea was measured by using a VAS score at each of the time intervals outlined, and a record was kept of any vomiting experienced by the patient.
A formal sample-size calculation was performed. From previous work, the SD of VAS pain scores was 1.2 cm. A two-sided significance level of 0.05 and a power of 80% were used against a specified mean difference of 0.7 cm. The calculated sample size was greater than 46 patients in each group. All enrolled patients completed the study. Statistical analysis was performed by using standard parametric and nonparametric statistics: one-way analysis of variance, Levene test of homogeneity of variances, the Mann-Whitney U-test, and Spearman’s correlation with significance assumed at the 5% level.
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Results |
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One hundred patients completed the study. Fifty-four patients were in Group A and received IP bupivacaine and IM meperidine. There were 46 patients in Group B, and these patients received IP bupivacaine and IP meperidine. The groups were well matched FOB demographics and operative details. There were no significant differences in age (36.9 [4.1] vs 36.6 [4.1] yr) or weight (62.8 [10.1] vs 64.1 [8.2] kg) between the two groups. In addition, there were no differences in the duration of pneumoperitoneum (11.0 [3.1] vs 11.7 [4.2] min) or the duration of surgery (21.5 [4.5] vs 21.9 [4.6] min).
At all time periods examined, the pain scores were significantly lower in Group B (the group receiving the IP meperidine) both at rest (Table 1) and on movement (Table 2). The greatest difference was seen at 2 h in the pain scores measured at rest and on movement, and the least difference between the groups was observed at 30 min both at rest and on movement.
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The time to first analgesia was not significantly different between groups (78 versus 60 min), but this was not significant. The need for further analgesia was examined by measuring the number of patients receiving either meperidine or acetaminophen and the average dose administered in those who received the drug (Table 3). There was no difference between the groups in either measurement.
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There were no significant differences between the nausea scores (nausea score at 30 min 0.3 [0.6] vs. 0.3 [0.7]) and the number of patients who vomited postoperatively in the two groups (vomited at 30 min, 2 versus 0).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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In the present study, the administration of IP meperidine resulted in significantly lower pain scores than the equivalent dose of meperidine administered IM in patients undergoing laparoscopic tubal ligation. The pain scores, both at rest and on movement, were significantly reduced by between one-third and two-thirds at each time period studied in those patients who received IP rather than an equivalent dose of IM meperidine. Although significant differences were observed in pain scores, no significant differences were observed for the time to additional analgesia and additional analgesia required during the study period. The procedure studied, laparoscopic tubal ligation, is performed as a day case, and the numbers required to observe a difference in these variables would be larger than the number required to observe a difference in pain scores.
Schulte-Steinberg et al. (11) examined pain after laparoscopic cholecystectomy in patients receiving IP morphine and found no analgesic effects. The opioid chosen for this study was meperidine, rather than morphine or fentanyl, because of the dual local anesthetic and analgesic properties of meperidine. The local anesthetic properties of meperidine appear to be superior to the other opioids. The effects of meperidine appear to be produced by its actions on two independent pathways: the opioid receptor pathways, which subserve analgesic action, and the sodium channels, which subserve local anesthetic action (12). These local anesthetic actions appear to be independent of its opioid analgesic activity when administered topically in the subarachnoid space, epidurally, or on exposed nerve in experimental studies. Interestingly, the effect of meperidine on nerve fiber subgroups may vary. In an in vitro study by Power et al. (12), examining the exposed vagus nerve, C fibers subserving pain were more sensitive to the effects of meperidine than A Fibers, even at low-frequency stimulation.
The local anesthetic actions of meperidine appear to be equivalent to those of lidocaine after subarachnoid administration (14). In the case of meperidine, the local anesthetic actions are sufficient for it to be used as a single drug for a subarachnoid block, and meperidine has the additional benefit of producing profound and prolonged analgesia (15,16).
Meperidine, aside from producing a local anesthetic effect when used alone, has also been shown to potentiate the degree of block produced by other established local anesthetics (13). Gobeaux and Landais (17) found that a combination of meperidine and lidocaine reduced postoperative analgesic requirements when the two drugs were combined for a brachial plexus block. Armstrong et al. (13) examined a combination of meperidine and prilocaine for IV regional anesthesia of the hand and forearm. Meperidine increased the speed of onset and the extent of sensory and motor block, reduced tourniquet and forearm pain, and subjectively improved the quality of the block. It also slowed the recovery of the neuromuscular blockade.
This study used a multimodal analgesic approach by using rectal diclofenac and IP bupivacaine and meperidine. The IP administration of meperidine has not been previously studied, but the local anesthetic properties, as well as the opioid analgesic effects, of meperidine made it an ideal drug for study. It proved effective and reduced pain scores both at rest and on movement at each time period studied. Although the VAS for pain were small in this study, significant differences were observed. These differences are clinically relevant when pain scores were more than halved at some time periods (Tables 2 and 3).
The effects of meperidine in our study may result from systemic activity. It is absorbed from the peritoneal cavity and has a central analgesic action. The speed of absorption and the rapidity of onset of action when administered by this route are uncertain in patients undergoing laparoscopy. Although the same dose of meperidine was administered IM in the control population, it is difficult to separate the local and systemic effects of meperidine in this study. In a previous study, the serum time concentration curves and pharmacokinetic variables of meperidine after IV and IM administration were compared. After 30 minutes, there was no significant difference between the serum time concentration curves, and after 2 hours, both serum time concentration curves were the same (18). Unfortunately, no similar data are available for the IP route, and measurement of serum levels of meperidine were not part of our protocol. Our results, which essentially compared the analgesic effects produced by equivalent doses of meperidine administered IM or IP, suggest that the observed differences may be produced by the local effects of meperidine, specifically its known local analgesic properties acting on the visceral peritoneum.
In this study, the combination of IP bupivacaine and IP meperidine was better than the combination of IP bupivacaine and IM meperidine for the relief of postoperative pain in patients undergoing laparoscopic tubal ligation. The use of IP meperidine has implications for patients undergoing laparoscopic procedures and merits further study.
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References |
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- Barkun JS, Barkun AN, Sampalis JS, et al. Randomised controlled trial of laparoscopic versus mini-cholecystectomy: a national survey of 4292 hospitals and an analysis of 77604 cases. Lancet 1992; 340: 1116–9.[Web of Science][Medline]
- Mc Mahon AJ, Russell IT, Baxter JN, et al. Laparoscopic versus minilaparotomy cholecystectomy: a randomised trial comparing postoperative pain and pulmonary function. Surgery 1994; 115: 533–9.[Web of Science][Medline]
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Rosenblum M, Weller RS, Conard P, et al. Ibuprofen provides longer lasting analgesia than fentanyl after laparoscopic surgery. Anesth Analg 1991; 73: 255–9.
[Abstract/Free Full Text] - Joris J, Thiry E, Paris P, et al. Pain after laparoscopic cholecystectomy: characteristics and effect of intraperitoneal bupivacaine. Anesth Analg 1995; 81: 379–84.[Abstract]
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Rademaker BPM, Kalkman CJ, Odoom JA, et al. Intraperitoneal local anaesthetics after laparoscopic cholecystectomy: effects on postoperative pain, metabolic responses and lung function. Br J Anaesth 1994; 72: 263–6.
[Abstract/Free Full Text] - Schulte-Steinberg H, Weninger E, Jokisch D, et al. Intraperitoneal versus interpleural morphine or bupivacaine for pain after laparoscopic cholecystectomy. Anesthesiology 1995; 82: 634–40.[Web of Science][Medline]
- Power I, Brown DT, Wildsmith JAW. The effect of fentanyl, meperidine and diamorphine on nerve conduction in vitro. Reg Anesth 1991; 16: 204–8.[Web of Science][Medline]
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Acalovschi I, Ene V, Lorinczi E, Nicolaus F. Saddle block with pethidine for perineal operations. Br J Anaesth 1986; 58: 1012–6.
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Sangarlankarn S, Klaewtanong V, Jonglerttrakool Khankaew V. Meperidine as a spinal anesthetic agent: a comparison with lignocaine-glucose. Anesth Analg 1987; 66: 235–40.
[Abstract/Free Full Text] - Gobeaux D, Landais A. Utilisation des deux morphiniques dans les blocs du plexus brachial. Cah Anesthesiol 1988; 36: 437–40.[Medline]
- Stambaugh JE, Wainer IW, Stanstead JK, Hemphill DM. The clinical pharmacology of meperidine: comparison of routes of administration. J Clin Pharmacol 1976; 16: 245–56.[Abstract]
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