|Year : 2016 | Volume
| Issue : 2 | Page : 93-97
Intraperitoneal instillation of ropivacaine plus dexmedetomidine for pain relief after laparoscopic hysterectomy: A comparison with ropivacaine alone
Sunil Chiruvella, Srinivasa Rao Nallam
Department of Anaesthesiology, Rims Kadapa, Andhra Pradesh, India
|Date of Web Publication||5-Jul-2016|
Department of Anaesthesiology, Rims Kadapa, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background and Aims: Intraperitoneal (IP) instillation of local anesthetics has been shown to minimize postoperative pain after laparoscopic surgeries. We compared the antinociceptive effects of IP dexmedetomidine combined with ropivacaine with that of IP ropivacaine alone in the patients undergoing laparoscopic hysterectomy.
Materials and Methods: At the end of laparoscopic hysterectomy, in a double-blind, randomized manner, one of the following injections was given intraperitoneally. The patients were allocated into the following two groups: The patients in ropivacaine group (R group) (N = 30) were given 30 mL of 0.2% ropivacaine plus 2 mL of normal saline; the patients in ropivacaine plus dexmedetomidine group (RD group) (N = 30) were given 30 mL of 0.2% ropivacaine combined with 1 μg/kg dexmedetomidine (diluted in 2 mL normal saline) through trocars. All the patients were given diclofenac sodium when they had pain [visual analogue scale (VAS) 3].
Results: VAS score at different time intervals, overall VAS in 24 h was significantly lower (1.86 ± 0.46 vs 4.7 ± 0.94), time to first request of analgesia (min) was longest (126 ± 24 vs 59 ± 13) and total analgesic consumption (mg) was lowest (95 ± 15 vs 175 ± 75) in RD group than in R group.
Conclusion: The antinociceptive effects of the intraperitoneal instillation of ropivacaine in combination with dexmedetomidine is superior to ropivacaine alone.
Keywords: Dexmedetomidine, intraperitoneal instillation, postoperative pain, ropivacaine
|How to cite this article:|
Chiruvella S, Nallam SR. Intraperitoneal instillation of ropivacaine plus dexmedetomidine for pain relief after laparoscopic hysterectomy: A comparison with ropivacaine alone. J NTR Univ Health Sci 2016;5:93-7
|How to cite this URL:|
Chiruvella S, Nallam SR. Intraperitoneal instillation of ropivacaine plus dexmedetomidine for pain relief after laparoscopic hysterectomy: A comparison with ropivacaine alone. J NTR Univ Health Sci [serial online] 2016 [cited 2020 Aug 11];5:93-7. Available from: http://www.jdrntruhs.org/text.asp?2016/5/2/93/185432
| Introduction|| |
The advantages of laparoscopic procedures over open procedures are as follows: Lesser hemorrhage; better cosmetic results; lesser postoperative pain; and shorter recovery time, leading to shorter hospital stay and less expenditure. 
Postoperative pain management remains a major challenge after laparoscopic procedures. Effective pain control encourages early ambulation, which significantly reduces the risk of deep vein thrombosis and pulmonary emboli (PE); enhances patient's ability to take deep breaths to decrease the risk of pulmonary complications (e.g., atelectasis and pneumonia); and decreases the incidence of tachycardia and unnecessary investigations related to it.
Pain after laparoscopic surgery has a visceral component, as a result of surgical handling and diaphragmatic irritation by dissolved carbon dioxide and a somatic component due to the holes made in the abdominal wall for the trocars.  Shoulder pain, which is associated with peritoneal insufflation, occurs especially when shoulder holders and an exaggerated Trendelenburg position are used that frequently complicate the postoperative period after the laparoscopic surgery.
Various methods have been tried to relieve postoperative pain following laparoscopic hysterectomy.  IP local anesthetics (IPLAs) alone or in combination with nonopioid analgesics have been used to reduce postoperative pain following gynecologic laparoscopy. , This might reduce adverse effects of opioids.
Ropivacaine, a newer analgesic, with a better toxicity profile compared with alternatives, such as bupivacaine, is currently considered the safest, long-acting local anesthetic available in the market.  Two trials comparing the plasma concentration after intravenous use of ropivacaine versus bupivacaine have demonstrated that ropivacaine requires a higher plasma concentration before toxicity develops.  Importantly as an IPLA, ropivacaine has been shown to be effective at reducing pain without developing clinical toxicity. , Dexmedetomidine is a selective alpha 2 (α2) adrenergic agonist with both analgesic and sedative properties. Its use in combination with ropivacaine is associated with prolongation of the LA effect either epidurally or intrathecally.
The aim of this study is to compare the antinociceptive effects of intraperitoneal (IP) dexmedetomidine combined with ropivacaine with that of IP ropivacaine alone in patients undergoing laparoscopic hysterectomy.
| Materials and methods|| |
Sixty patients, with the American Society of Anesthesiologists (ASA) physical status 1 and 2, aged between 45 years and 60 years, undergoing elective laparoscopic hysterectomy under general anesthesia at the Rajiv Gandhi Institute of Medical Sciences College and Hospital, Kadapa, Andhra Pradesh, were randomized into two groups. The following patients were excluded from the study: Patients belonging to ASA physical status 3, 4, and 5; patients with history of left ventricular failure, atrioventricular conduction block, uncontrolled diabetes, and hypertension; and patients taking beta-blocking drugs.
The study protocol was approved by the Institutional Ethical Committee. Written informed consent was taken from each subject who is willing to enter the study. Preanesthetic checkup and routine investigations, such as complete blood count test, serum creatinine level test, and electrocardiogram (ECG), were done. The patients were kept nil by mouth for 6 h. All patients received clonazepam tablet (0.5 mg) orally on the night before the surgery. Sixty ASA grade I and II patients undergoing elective laparoscopic hysterectomy were randomly assigned to one of the two groups: Ropivacaine group (R group) and ropivacaine plus dexmedetomidine group (RD group). The patients were premedicated with glycopyrrolate 0.004 mg/kg in the preoperative room.
On arrival to operating room, an 18-gauge intravenous (IV) catheter was inserted and 6 mL/kg/h crystalloid was infused. Noninvasive monitors, such as electrocardiography, noninvasive blood pressure (NIBP), oxygen saturation (SpO 2 ), were attached and baseline parameters such as heart rate, systemic arterial pressure, and peripheral oxygen saturation and level of sedation were noted down.
After preoxygenation for 3 min, anesthesia was induced with a standard anesthetic protocol using midazolam (0.05 mg/kg), fentanyl (2 μg/kg), and propofol (2 mg/kg) followed by succinylcholine (2 mg/kg) to facilitate tracheal intubation; trachea was intubated with an appropriate sized cuffed, endotracheal tube. Lungs were mechanically ventilated with O 2 -N 2 O (33-66%), sevoflurane 0.8% MAC, and vecuronium bromide 0.1 mg/kg bolus followed by 1 mg intermittently for neuromuscular blockade. Tidal volume and ventilator frequency were adjusted to maintain normocapnia (EtCO 2 40 ± 4 mmHg). Pneumoperitoneum (PP) was created by insufflations of CO 2 and the operation table was tilted to about 15° Trendelenburg. Intra-abdominal pressure was not allowed to exceed 15 mmHg.
At the end of the procedure, those patients who were allocated to RD group received 32 mL of ropivacaine plus dexmedetomidine (30 mL of 0.2% ropivacaine combined with 1 μg/kg dexmedetomidine diluted in 2 mL of normal saline), intraperitoneally. A total of 16 ml of solution was instilled on the inferior aspect of diaphragm (8 ml on each side) and remaining 16 ml on the operative site via the umbilical port site with patient in anti-Trendelenburg position (after peritoneal wash and suctioning). In the patients allocated to R group, 32 mL of solution (30 mL of 0.2% ropivacaine plus 2 mL of normal saline) was instilled in the same pattern. CO 2 was then evacuated from the peritoneal cavity and the skin incision was sutured.
At the end of the operation, neuromuscular blockade was antagonized with injection of neostigmine (0.05 mg/kg) and glycopyrrolate (0.008 mg/kg) intravenously and the patient was extubated when respiration was deemed sufficient and they were able to obey commands. The patients were transferred to recovery room. In the postanesthesia care unit (PACU), they were monitored for any evidence of complications or adverse events.
Before the induction of anesthesia, the patients were instructed on how to use a 0-10 visual analogue scale (VAS; with end point to be labeled "no pain" and "worst possible pain"). The degree of postoperative pain was assessed using the VAS at 30 min, 1 h, 4 h, 8 h, 12 h, 16 h, and 24 h postoperatively. Those patients who had VAS >4, were administered a bolus of diclofenac aqueous (75 mg) as rescue analgesia. Ondansetron (4 mg i.v.) was administered on complaint of nausea and vomiting. Time to first analgesic requirement after completion of surgery, total analgesic requirement in the first 24 hrs postoperatively for each patient and occurrence of adverse events in the postoperative period, was also recorded.
| Results|| |
There was no significant difference with respect to age, sex, weight, and ASA physical status of the patients; duration of surgery; and anesthesia time [Table 1]. VAS at different time intervals were statistically significantly lower at all times in RD group compared to R group [Table 2].
Regarding the pattern of pain, it was predominantly of generalized abdominal type of pain occurring patients from both the groups [Table 3], followed by incisional pain. None of the patients complained of shoulder pain. Only one patient from R group complained of perineal pain.
Furthermore, overall VAS in 24 h was also significantly lower in RD group (1.86 ± 0.46) compared to R group (4.7 ± 0.94) [Table 4]. Time required for first dose of rescue analgesia was longerin the RD group (126 ± 24 min) than in R group (59 ± 13 min), indicating better and longer pain relief in the RD group compared to R group. The difference was also statistically significant among the two groups [Table 4]. Total analgesic consumption was high in R group than in RD group [Table 4]. Total diclofenac consumption was also low in RD group (95 ± 15 mg) than in R group (175 ± 75 mg) [Table 4].
Three patients in RD group and six patients in R group complained of nausea. One patient (3%) in RD group and four patients (13.3%) in R group complained of vomiting. The incidence of shoulder pain was significantly higher in R group (60%) than in RD group (10%). There was no incidence of pruritus, excessive sedation, drowsiness, or dryness of mouth in both the groups [Table 5].
| Discussion|| |
IPLAs have been used since the time as early as 1950. IPLA has been used to reduce shoulder tip pain, overall pain, nausea and vomiting, and the time of hospital stay.  Recently, peripheral use of local anesthetics for postoperative pain relief has become a popular practice after laparoscopy surgery. Among the several local anesthetic techniques used for pain relief that are currently in practice, such as transcervical injection and rectus sheath blockade, the instillation of local anesthetic intraperitoneally has been the most promising. 
The reason for choosing the IP route is to block the visceral afferent signaling, and thereby potentially modifying visceral nociception and providing analgesia. The local anesthetic inhibits nociception by affecting nerve membrane associated proteins and by inhibiting the release and action of prostaglandins and other agents that sensitize or stimulate the nociceptors and contribute to inflammation. However, absorption from large peritoneal surface may also occur, which may be a further mechanism of analgesia.
Ropivacaine (l-propyl-2′, 6′-pipecoloxylidide hydrochloride), a new long-acting amide local anesthetic that is formulated as the pure S-enantiomer, is chemically related to bupivacaine, but it has been shown to be less toxic to cardiac and central nervous systems.  This drug possesses anti-inflammatory activity that may further reduce pain when administered locally.  The antinociceptive effect of dexmedetomidine is seen at dorsal root neuron level, where it blocks the release of substance P in the nociceptive pathway, through action on inhibitory G protein, which increases the conductance through potassium channels. 
The rationale of preferring ropivacaine in our study is that it is a long-acting agent (6-12 h), which has less motor blockade and less cardiotoxicity than bupivacaine. We have provided nearly total blocks by giving the local anesthetic agents to all regions where many surgical manipulations were applied, such as hepatoduodenal ligament, gallbladder bed, and subdiaphragmatic and subhepatic areas. Through this application, we have decreased the pain of the patients in a satisfactorily. The fact that the in general and after coughing VAS scores were statistically significant between the R and RD groups shows us that ropivacaine combined with dexmedetomidine is more effective than ropivacaine alone. Ropivacaine combined with dexmedetomidine decreases the opioid consumption and nausea in the first 24 h more significantly than ropivacaine alone.
One previous study by Goldstein et al. reported that the IP instillation of 20 mL of either 0.5% bupivacaine or 0.75% ropivacaine prevented postoperative pain and decreased the need for postoperative analgesia, when compared with placebo in patients undergoing laparoscopic gynecologic surgery.  Another study by Callesen et al. combined port site and mesosalpinx infiltration and peritoneal instillation by using 285 mg of ropivacaine (50 mL) in a double-blind, randomized, placebo-controlled study on 80 patients undergoing laparoscopic tubal sterilization. 
Also Narchi et al. found that IP instillation of local anesthetics are more effective in reducing pain upto 48 h postoperatively in patients undergoing diagnostic laparoscopy.  Subsequent studies failed to demonstrate the beneficial effect of IP instillation of local anesthetics in patients undergoing laparoscopic cholecystectomy. Utilizing 20 mL of either 0.25% bupivacaine or 0.5% lignocaine, Rademaker et al. failed to demonstrate any reduction in postoperative pain. One possible explanation of the failed effect by Narchi et al., was the small amount of local anesthetics used. Also instillation of local anesthetics in the supine position prevented its flow over the coeliac plexus and phrenic nerve endings.
The results of the present study suggest that the IP instillation of ropivacaine combined with dexmedetomidine was more effective in reducing pain immediately after operative laparoscopy when compared with the IP instillation ropivacaine alone. The pain scores and analgesic requirement in the RD group were lower than those in R group during the first hour after surgery, but cumulative analgesic consumption in 24 h was similar in all groups.
Bisgaard et al. suggested that pain after laparoscopic cholecystectomy was divided into three components: Incisional pain, which dominated over visceral pain, which in turn dominated over shoulder pain.  Several investigators have reported that the visceral pain experienced after laparoscopic cholecystectomy can be theoretically blocked by IP instillation.  In the present study, IP instillation with ropivacaine or ropivacaine combined with dexmedetomidine was found to be effective in preventing visceral pain after gynecologic laparoscopy. The results of the present study seems to be in accordance with the findings of Bisgaard et al. 
Shoulder pain is a common outcome and frequent complication after laparoscopic hysterectomy and can delay return to normal activities. It has been reported in 35-63% of cases.  It occurs after diaphragmatic stretching with phrenic nerve neuropraxia. The incidence of shoulder pain is markedly lower in laparoscopic hysterectomy when compared to laparoscopic cholecystectomy.  We found a low incidence of shoulder pain in all treatment groups, because the residual IP CO 2 was carefully removed by the surgeon.
Although we did not encounter pruritus, excessive sedation, drowsiness, or dryness of mouth in the both the groups, in the first postoperative 24 h, nausea occurred in six patients in R group in the postoperative period. This finding is statistically significant.
| Conclusion|| |
We conclude that IP instillation of dexmedetomidine (1 μg/kg) in combination with ropivacaine 0.2% in elective laparoscopic hysterectomy significantly reduces the postoperative pain and significantly reduces the analgesic requirement in the postoperative period as compared to ropivacaine 0.2% alone.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kim TH, Kang HK, Park JS, Chang IT, Park SG. Intraperitoneal ropivacaine instillation for postoperative pain relief after laparoscopic cholecystectomy. J Korean Surg Soc 2010;79:130-6.
Pasqualucci A, de Angelis V, Contardo R, Colò F, Terrosu G, Donini A, et al
. Preemptive analgesia: Intraperitoneal local anesthetic in laparoscopic cholecystectomy. A randomized, double-blind, placebo-controlled study. Anesthesiology 1996;85:11-20.
Abdulla S, Eckhardt R, Netter U, Abdulla W. A randomized, double-blind, controlled trial on nonopioid analgesics and opioid consumption for postoperative pain relief after laparoscopic cholecystectomy. Acta Anaesthesiol Belg 2012;63:43-50.
Khan MR, Raza R, Zafar SN, Shamim F, Raza SA, Pal KM, et al
. Intraperitoneal lignocaine (lidocaine) versus bupivacaine after laparoscopic cholecystectomy: Results of a randomized controlled trial. J Surg Res 2012;178:662-9.
Goluboviæ S, Goluboviæ V, Cindriæ-Stancin M, Tokmadziæ VS. Intraperitoneal analgesia for laparoscopic cholecystectomy: Bupivacaine versus bupivacaine with tramadol. Coll Antropol 2009;33:299-302.
Graf BM. The cardiotoxicity of local anesthetics: The place of ropivacaine. Curr Top Med Chem 2001;1:207-14.
Marks JL, Ata B, Tulandi T. Systematic review and metaanalysis of intraperitoneal instillation of local anesthetics for reduction of pain after gynecologic laparoscopy. J Minim Invasive Gynecol 2012;19: 545-53.
Labaille T, Mazoit JX, Paqueron X, Franco D, Benhamou D. The clinical efficacy and pharmacokinetics of intraperitoneal ropivacaine for laparoscopic cholecystectomy. Anesth Analg 2002;94:100-5, table of contents.
Kucuk C, Kadiogullari N, Canoler O, Savli S. A placebo-controlled comparison of bupivacaine and ropivacaine instillation for preventing postoperative pain after laparoscopic cholecystectomy. Surg Today 2007;37:396-400.
Kahokehr A, Sammour T, Soop M, Hill AG. Intraperitoneal local anaesthetic in abdominal surgery - A systematic review. ANZ J Surg 2011;81:237-45.
Liu SS, Hodgson PS. Local anaesthetics In: Barash PG, Cullen BF, Stoelting RK, editors. Clinical Anaesthesia. 4 th
ed. Philadelphia: Lippicott Williams & Wilkins; 2001. p. 449-69.
Moller R, Covino BG. Cardiac electrophysiologic properties of bupivacaine and lidocaine compared with those of ropivacaine, a new amide local anesthetic. Anesthesiology 1990;72:322-9.
Karamanlioglu B, Turan A, Memis D, Kaya G, Ozata S, Ture M. Infiltration with ropivacaine plus lornoxicam reduces postoperative pain and opioid consumption. Can J Anaesth 2005;52:1047-53.
Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology 2000;93:1345-9.
Goldstein A, Grimault P, Henique A, Keller M, Fortin A, Darai E. Preventing postoperative pain by local anesthetic instillation after laparoscopic gynecologic surgery: A placebo-controlled comparison of bupivacaine and ropivacaine. Anesth Analg 2000;91:403-7.
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;82:586-90.
Narchi P, Benhamou D, Fernandez H. Intraperitoneal local anaesthetic for shoulder pain after day-case laparoscopy. Lancet 1991;338:1569-70.
Bisgaard T, Klarskov B, Kristiansen VB, Callesen T, Schulze S, Kehlet H, et al
. Multi-regional local anesthetic infiltration during laparoscopic cholecystectomy in patients receiving prophylactic multi modal analgesia: A randomized, double-blinded, placebo-controlled study. Anesth Analg 1999;89:1017-24.
Helvacioglu A, Weis R. Operative laparoscopy and postoperative pain relief. Fertil Steril 1992;57:548-52.
Louizos AA, Hadzilia SJ, Leandros E, Kouroukli IK, Georgiou LG, Bramis JP. Postoperative pain relief after laparoscopic cholecystectomy: A placebo-controlled double-blind randomized trial of preincisional infiltration and intraperitoneal instillation of levobupivacaine 0.25%. Surg Endosc 2005;19:1503-6.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]