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Department of Anesthesia, Rotunda Hospital, Parnell Square, Dublin, Ireland
Address correspondence and reprint requests to Dr. Sallyann Colbert, Department of Anesthesia, Mater Hospital, Eccles St., Dublin, Ireland.
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Abstract |
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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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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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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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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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Discussion |
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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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This article has been cited by other articles:
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  M. J. Paech, K. F. Ilett, L. P. Hackett, M. Page-Sharp, and R. W. Parsons Disposition and Clinical Outcome After Intraperitoneal Meperidine and Ropivacaine Administration During Laparoscopic Surgery Anesth. Analg., January 1, 2008; 106(1): 278 - 286. [Abstract] [Full Text] [PDF]
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 A. Ng and G. Smith Editorial I: Intraperitoneal administration of analgesia: is this practice of any utility? Br. J. Anaesth., October 1, 2002; 89(4): 535 - 537. [Full Text] [PDF]
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