Original Articles

A clinical comparative study of intraperitoneal instillation of ropivacaine alone or ropivacaine with nalbuphine for postoperative analgesia in laparoscopic cholecystectomy

Sanjay Singh1, M. K. Giri2, Mayurika Singh3,  Navin Kumar Giri4

1Assistant Professor; 4Postgraduate  Resident, Department of Surgery, Moti Lal Nehru  (MLN) Medical College , Allahabad  211002, Uttar Pradesh (India)

2Assistant Professor, Department of Anesthesiology, Moti Lal Nehru  (MLN) Medical College, Allahabad  211002, Uttar Pradesh (India)

3Assistant Professor, Department of Radiodiagnosis, Moti Lal Nehru  (MLN) Medical College, Allahabad 211002, Uttar Pradesh (India)

Correspondence: Dr Manoj Kumar Giri, PMS Quarters No. 4, SRN Hospital Campus, Allahabad 211002, Uttar Pradesh (India); Phone: +9044479649; E-mail: drmanoj.giri@gmail.com


Background & objectives: Intraperitoneal instillation of local anesthetic agents with or without opioids has been proposed to reduce postoperative pain after laparoscopic procedures. So, we did a prospective, randomized, double blind, placebo-controlled study to compare the effectiveness of intraperitoneal 0.2% ropivacaine alone or with nalbuphine for postoperative analgesia in laparoscopic cholecystectomy.

Methodology: A total of 90 patients of ASA class I and II for laparoscopic cholecystectomy procedures were enrolled for this study. The drug was instilled intraperitoneally before the removal of trocar at the end of surgery. In Group-1 (n=30): 0.2% ropivacaine + 2 mg nalbuphine in 20 ml, in Group-2 (n=30): 20 ml 0.2% ropivacaine alone and in Group-3 (n=30) normal saline 20 ml were installed intraperitoneally. Postoperative pain was assessed by visual analogue score for 24 hours and when VAS >4, rescue analgesic was administered. The total amount of rescue analgesics given in the postoperative period and side effects were noted in this study.

Results: Intraperitoneal instillation of ropivacaine with nalbuphine significantly reduced immediate postoperative VAS scores (1.0667 ± 0.78, 3.36 ± 1.37 and 5.53 ± 1.85 in Group-1, 2 and 3 respectively). It also reduced VAS at 8 hours after surgery in the Group-1 (0.8 ± 0. 71) compared to the Group-2 VAS (2.73 ± 1.25). The time for the first rescue analgesic requirement was significantly higher in Group-1 (6.15 h) compared to the Group-2 (4.51 h). Total amount of rescue analgesic was required more in Group-2 and Group-3 compared to Group-1.

Conclusion: Addition of nalbuphine to intraperitoneal ropivacaine significantly prolonges the time to first rescue analgesic requirement and reduces the total consumption of rescue analgesics in 24 hours without any significant increase in adverse events in laparoscopic cholecystectomies.

Key words: Ropivacaine; Intraperitoneal Instillation; Nalbuphine; Postoperative analgesia

Citation: Singh S, Giri MK, Singh M, Giri NK. A clinical comparative study of intraperitoneal instillation of ropivacaine alone or ropivacaine with nalbuphine for postoperative analgesia in laparoscopic cholecystectomy. Anaesth Pain & Intensive Care 2017;21(3):335-339

Received – 21 Feb 2017; Reviewed – 21 Feb, 17 Aug 2017; Corrected – 28 April, 22 Aug 2017; Accepted – 22 Aug 2017


Laparoscopic surgical procedures have almost replaced open surgical procedures because of better and smaller incision, minimal bleeding, less postoperative pain and shorter stays in postoperative period.1,2,3 Mild to moderate postoperative pain in laaproscopic surgeries is mostly in the upper abdomen, shoulder tip and back regions. Postoperative pain is more common during the first few hours after surgery and usually reduces over the next 48 to 72 hours.4 Intra-abdominal cavity stretching, peritoneal and diaphragmatic irritation caused by residual carbon dioxide is most common factors responsible for postoperative pain 5,6. Local anesthetics agents instillation over intraperitoneum have been used to minimize postoperative pain after laparoscopic surgery7. Local anesthetics have been studied for post operative pain relief by instillation over the peritoneal cavity for minimally invasive procedures, such as laparoscopic cholecystectomy and gynecological laparoscopy.8 Addition of narcotics was thought to be useful in prolongation of the analgesia.

We conducted this prospective, randomized, double blind, placebo-controlled study to compare the effectiveness of intraperitoneal 0.2% ropivacaine alone or with nalbuphine for postoperative analgesia in laparoscopic cholecystectomy.


After permission from the institutional ethical committee, a total of ninty adult patients of both sexes between ages 18 to 60 years, ASA I and II, undergoing elective laparoscopic cholecystectomy were divided randomly into three groups of 30 patients each in every group.

Patients were briefed about the visual analogue scale (VAS) on the day previous to the surgery and a detailed explanation of the same was given. The patients were divided into three groups after computer generated randomization and blinding.

Group-1 (n=30): received 20 ml of 0.2% ropivacaine along with 2 mg of nalbuphine

Group-2 (n=30): received 20 ml 0.2% ropivacaine

Group-3 (n=30): received 20 ml of normal saline as placebo

General anesthesia protocol:

All patients were pre-medicated 30 min before with fentanyl 2.0 μg/kg, glycopyrrolate 0.2 mg and ondansetron 0.1 mg/kg with inj midazolam 30 μg /kg intravenously. Preoxygenation was carried out for 3 min with 100% oxygen, and anesthesia was induced with inj propofol (2-2.5 mg/kg) till loss of verbal commands + inj succinylcholine (1.5-2 mg/kg) IV. Intubation by the oral route was done with cuffed PVC endotracheal tube of appropriate size.

Maintenance of anesthesia done with 50:50 N2O + O2 + isoflurane (0.5-1.0%) + inj vecuronium (0.02-0.04 mg/kg). Mechanical ventilation, with tidal volumes 8 – 10 ml/kg, was adjusted to maintain end-tidal carbon dioxide (EtCO2) between 35 and 40 mmHg. During laparoscopy, intra-abdominal pressure was limited to 10 – 12 mmHg. Non depolarizing muscle blockade was reversed with inj neostigmine 0.05 mg/kg + glycopyrrolate 0.01 mg/kg.

Intra operative monitoring consisted of ECG, NIBP, EtCO2 and pulse oximeter. The study drugs were instillated intraperitoneally before the removal of trocar in equal volumes from all the ports.

In the Post-anesthesia Care Unit ( PACU) the Visual analogue scale (VAS), Ramsay sedation score and PONV Intensity Scale were used to assess each patient. Postoperative pain assessment was done using VAS score of 0-10 (0 = No pain, 10 = Worst imagined 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 intravenous as rescue analgesia. Breakthrough pain was controlled with inj tramadol 1.0 mg/kg in increments up to a maximum dose of 2 mg/kg. Postoperative complications, e.g. pain, nausea and vomiting, hypotension, bradycardia and itching etc. were be assessed at the above times. Nausea and vomiting, need of any rescue analgesics for pain, any voiding problems, respiratory difficulties were documented by proforma vide infra. Inj Ondansetron 0.1 mg/kg was given intravenously for vomiting.

Statistical data: Data were presented as mean ± SD or proportion (%). Statistical analysis was performed on SPSS version 12.0 along with an ANOVA test and a P < 0.05 was considered significant.


A total of 90 patients participate in this study, and they were subsequently enrolled (n = 30 per group), with no patient dropouts. The groups were similar with respect to age, sex, weight , height and duration of surgery (Table 1).

Table 1: Baseline characteristics

Variable Group1 Group-2 Group-3 p value
Age (Yrs) 37.6 ± 12.28 36.89 ± 12.59 40.60 ± 11.09 0.454
Sex (M:F) 07:23 09:21 12:18 0.628
Weight (Kg) 50.23 ± 4.62 50.33 ± 4.45 50.9 ± 4.93 0.837
Height (cm) 149.83 ± 5.92 149.76 ± 5.91 150.16 ± 6.04 0 .961
Duration of
surgery (minutes)
82.2 ± 8.25 89.2 ± 8.69 81.6 ± 8.73 0.36

VAS scores were found lower in the ropivacaine with nalbuphine group (1.0667 ± 0.78) as compared to the ropivacaine alone and saline group, 3.36 ± 1.37 and 5.53 ± 1.85 in Group-2 and 3 respectively) (Table 2).

Table 2: Mean visual analogue scale pain score. Data given as Mean ± SD

Group Immediately
After Surgery
1 h 4 h 8 h 12 h 16 h 24 h
Group-1 1.0667 ± 0.78 0.4 ± 0.49 0.56 ± 0.50 0.8 ± 0.71 2.3 ± 1.02 3.56 ± 0.89 4.53 ± 1.45
Group-2 3.36 ± 1.37 1.73 ± 1.87 2.8 ± 1.62 2.73 ± 1.25 3.96 ± 1.49 4.46 ± 1.04 5 ± 0.83
Group-3 5.53 ± 1.85 5.06 ± 1.31 1.6 ± 0.49 2.26 ± 0.78 2.86 ± 0.86 5.46 ± 1.88 7.16 ± 0.69
p value < .0001 < .0001 < .0001 < .0001 < .0001 < .0001 < .0001

In saline group, 50 % of the patients demanded the rescue analgesia within the 1st postoperative period. Patients of Group-1 demanded the first dose of rescue analgesic in the 4th postoperative hours.

Normal saline group required more frequent dosing. Total doses of rescue analgesia were lowest in nalbuphine with ropivacaine group and highest in normal saline group (Table 3).

Table 3: Number of patients require rescue analgesics. Data given as N (%)

Time Interval Group-1 (n=30) Group-2 (n=30) Group-3 (n=30)
Immediate postoperatively 0 (0) 7 (0.23) 16 (0.53)
1st postoperative hour 0 (0) 7 (0.23) 12 (0.4)
4st postoperative hour 1 (0.033) 9 (0.3) 10 (0.33)
8st postoperative hour 7 (0.23) 7 (0.23) 14 (0.46)
12st postoperative hour 8 (0.26) 15 (0.5) 17 (0.56)
16st postoperative hour 11 (0.36) 16 (0.53) 25 (0.83)
24st postoperative hour 17 (0.56) 20 (0.66) 30 (100)
Total dose of rescue analgesia required in the group over 24  h period 44 81 124

Time to request for the first dose rescue analgesia was longer in the ropivacaine with nalbuphine group than ropivacaine group or saline group . Total analgesic consumption was maximum in saline group and minimum in ropivacaine with nalbuphine group (Table 3).

The incidence of pruritis was more with ropivacaine with nalbuphine group than other groups, but this difference was found to be statistically non-significant (p = 0.084). Postoperative emesis was more in normal saline group. Incidence of hypotension and bradycardia was more in Group-1 than other groups but this difference was found to be non-signigicant. Shoulder pain was not observed in any of the three groups in the first 8 h postoperatively; however, after 8 h, its incidence was statistically significant in saline group patients. No shoulder pain was observed in patients receiving ropivacaine alone or with nalbuphine even after 8 h postoperatively (Table 4).

Table 4: Incidence of pruritus, emesis, hypotension, bradycardia and shoulder pain in three groups [N

Adverse effects Group-1
(n = 30)
(n = 30)
(n = 30)
p value
Pruritus 6 (20) 2 (6) 1 (3) 0.084
Emetic symptoms 4 (10) 3 (10) 9 (30) 0.069
Hypotension 3 (10) 0 (0) 1 (3) 0.166
Bradycardia 9 (30) 1 (3) 1 (3) 0.002
Shoulder pain 0 (0) 0 (0) 6 (20) < 0.001


Sedation level of the patients was assessed based on the Ramsey sedation scale. Sedation scores were statistically higher in the ropivacaine with nalbuphine group as compared with ropivacaine alone or saline group in immediate postoperative period (Table 5).

Table 5: Postoperative Ramsay Sedation Scale (RSS) [Mean ± SD]

Time period  Group1 Group-2 Group-3 p value
Immediate postoperatively(RSS) 4.56 ± 0.50 2.40 ± 0.50 2.26 ± 0.44 < .001
1st postoperative hour (RSS) 3.96 ± 0.49 1.93 ± 0.25 1.90 ± 0.30 < .001
4st postoperative hour (RSS) 2.43 ± 0.50 1.83 ± 0.37 1.66 ± 0.47 < .001
8st postoperative hour (RSS) 2.26 ± 0.44 1.73 ± 0.44 1.43 ± 0.50 < .001
12st postoperative hour (RSS) 1.50 ± 0.50 1.26 ± 0.44 1.06 ± 0.25 < .065
16st postoperative hour (RSS) 1.33 ± 0.47 1.20 ± 0.40 1.00 ± 0.00 < .0253
24st postoperative hour (RSS) 1.10 ± 0.35 1.13 ± 0.34 1.03 ± 0.18 0.392

Postoperative pain from laparoscopic surgeries is mainly due to stretching of visceral and parietal peritoneum and referred shoulder pain. All of these differ from each other in the form of intensity, latency and duration.9 We found that pain intensity was lower in patients who received intraperitoneal nalbuphine with ropivacaine compared with those who received intraperitoneal saline during the first 8 h after recovery. The total dose of rescue analgesics used was markedly reduced in patients with intraperitoneal ropivacaine and nalbuphine group.

Kang H et al10, studied intraperitoneal instillation of ropivacaine for postoperative pain relief in laparoscopic appendectomy and found lower fentanyl consumption as rescue analgesic in the ropivacaine group as compared to placebo, this also supports our study in which reduced requirement of rescue analgesic diclofenac in ropivacaine alone and ropivacaine with nalbuphine as compare to placebo saline group. Previous studies11,12,13 in different types of laparoscopic surgeries with intraperitonial ropivacaine also support our result for better postoperative pain relief. Opioids intraperitoneally like morphine14,15, fentanyl 16, or tramadol17,18,19 have shown good results in postoperative analgesia and also support our results, but we did not find any previous study in which intraperitoneal nalbuphine was administered for postoperative pain relief.

Contrary to our findings, Ali et al.20 did not find appreciable analgesia in patients undergoing abdominal hysterectomy for intraperitoneal administration of a local anesthetic into the pelvic cavity. Schulte-Steinberg et al.21 also did not find significant analgesia after intraperitoneal morphine in laparoscopic cholecystectomy.

The incidence of shoulder pain was lower in intraperitoneal nalbuphine or ropivacaine group compared with the control saline group. Narchi et al.12 showed that there was less postoperative shoulder pain with intraperitoneal saline plus lidocaine. However, previous studies17,18 with intraperitoneal opioids found a non-significant difference for shoulder pain as compared to placebo. This was not in agreement with our results, because none of these studies used intraperitoneal nalbuphine.

PONV was greater in patients with intraperitoneal nalbuphine or saline than in patients given intraperitoneal ropivacaine alone. However, previous studies21,22 did not show any statistical difference between patients given either intraperitoneal local anesthetics or opioids for the incidence of PONV.


The combination of intraperitoneal ropivacaine and nalbuphine is superior to plain ropivacaine for reducing postoperative pain in patients undergoing laparoscopic surgery, without any significant increase in adverse events. Ropivacaine with or without nalbuphine reduces not only the intensity of pain, but also the total dose of rescue analgesic consumption. Ropivacaine alone or with nalbuphine also reduces the incidence of shoulder pain, but bradycardia was significantly higher in these patients. Therefore, we conclude that intraperitoneal instillation of ropivacaine with nalbuphine reduces not only the intensity of visceral, parietal and shoulder pain but also the total rescue analgesic dose consumption.

Source of Support: Nil

Conflict of Interest: None declared

Authors Contribution:

SS: conduct of study and literature search

MKG: Design of study and manuscript editing

MS: Study analysis and literature research

NKG: conduction of study work and statistical analysis



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