Comparative study of postoperative analgesic effect of intraperitoneal instillation of dexmedetomidine with bupivacaine and bupivacaine alone after laparoscopic surgery.

AIMS: This prospective double-blinded study was designed with the aim of comparing the analgesic effect of intraperitoneal instillation of dexmedetomidine with bupivacaine with that with bupivacaine alone in patients undergoing laparoscopic surgeries.
MATERIALS AND METHODS: A total of 100 patients of either sex undergoing elective laparoscopic surgery were randomly divided into two groups containing 50 patients in each group. Group B received intraperitoneal instillation with 50 mL of bupivacaine 0.25% (125 mg) and groups B + D received 50 mL of bupivacaine 0.25% (125 mg) + 1 μg/kg of dexmedetomidine. Pain was assessed using visual analogue scale (VAS) at 0.5 h, 1 h, 2 h, 4 h, 6 h, and 24 h after the surgery. The requirement of rescue analgesics were recorded. RESULT: Duration of analgesia was longer in group B+D (14.5 hr) compared to group B (13.06 hr). The requirement of rescue analgesic in 24 hours was less in group B+D (1.76) compared to group B (2.56) which were statistically significant (P < 0.05). The mean number of total rescue analgesia given in 24 h was less in group B+D was 1.76 whereas in group B was 2.56 that were statistically significant.
CONCLUSION: Intraperitoneal instillation of dexmedetomidine with bupivacaine prolongs the duration of postoperative analgesia as compared to that with bupivacaine alone. And also there is less number of rescue analgesics that are required postoperatively when dexmedetomidine is supplemented as an adjuvant to bupivacaine.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Laparoscopic surgery is a modern surgical technique used for various surgeries such as cholecystectomy, appendectomy and hernia repair. There are a number of advantages of this technique including reduced pain and bleeding, shorter recovery time and hospital stay, and over all reduced healthcare costs.[1] The type of pain after laparoscopic surgery differs considerably from that occurs after laparotomy. Usually patients experience diffuse pain in abdomen, back and shoulder.

Pain intensity usually peaks during the first postoperative period and usually declines over the following 2-3 days.[2] Pain after laparoscopic surgery results from the stretching of the intra-abdominal cavity,[3] peritoneal inflammation and phrenic nerve irritation caused by residual carbon dioxide (CO2) in the peritoneal cavity. Pain can prolong hospital stay and lead to increased morbidity. Intraperitoneal injections of local anaesthetic have been proposed to minimize postoperative pain after laparoscopic surgery.[4]

The α2-adrenergic agonist provides sedation, anxiolysis, analgesia and sympatholysis. Dexmedetomidine has become one of the frequently used drugs in anaesthesia due to its hemodynamic, sedative, anxiolytic, analgesic, neuroprotective and anaesthetic sparing effect. High selectivity of dexmedetomidine to α2- receptors has been exploited in regional anaesthesia practice.

The purpose of this study was to compare the antinociceptive effect of intraperitoneal application of bupivacaine and bupivacaine in combination with dexmedetomidine after laparoscopic surgery.

MATERIALS AND METHODS

After approval from Institutional Ethics Committee 100 patients posted for laproscopic surgery under general anaesthesia were enrolled for the study. Inclusion criteria: patients belonging to American Society of Anaesthesioly (ASA) I and II, age between 25 to 60 years, elective laproscopic surgeries. The patients with previous abdominal surgery, drug allergy, cardiac patients, significant pulmonary diseases and leaving intra-abdominal drain at the end of the surgery were excluded from the study. In the operating room (OR) intravenous (IV) line was secured. Inj. Ringer Lactate infusion started with 8 ml/kg patients were premedicated with Inj. Glycopyrrolate 4 μg/kg i.v., Inj Ranitidine 50 mg i.v., Inj. Ondansetron 4 mg i.v.

Electrocardiogram (ECG), saturation of oxygen (SpO2) and non invasive blood pressure were monitored. All the patients received fentanyl in dose of 1.5 mg/kg i.v. Anaesthesia induction done with sodium thiopentone 4-6 mg/kg and succinylcholine 1.5-2 mg/kg i.v to facilitate intubation. All patients were intubated with appropriate sized oral cuffed endotracheal tube. Anaesthesia was maintained with nitrous oxide and oxygen mixture (50:50) with sevoflurane. Ventilation is adjusted to maintain EtCO2 between 36-42 mm of Hg. Pneumoperitoneum pressure was kept between 8-12 mm of Hg throughout the surgery. Vecuronium was used to maintain intraoperative neuromuscular blockade. Intravenous 75 mg diclofenac sodium was given intraoperatively in all patients. Intraoperative pulse, mean blood pressure (MBP), SpO2 and EtCO2 were monitored. Complete revisions of haemostasis were confirmed before the intraperitoneal instillation of the drug.

The patients were randomly allocated (using table of randomization) into two equal sized groups (N = 50):

Group (B): Intraperitoneal 50 mL bupivacaine 0.25% (125 mg)

Group (B+D): Intraperitoneal 50 mL bupivacaine 0.25% (125 mg) + 1 μg/kg dexmedetomidine

The drugs were prepared and given to the investigators who were blind to the identity of drugs.

In the two study groups, at the end of surgery, intraperitoneal instillations were guided by the camera on the surgical site and under both the copulae of the diaphragm. The intensity of the pain was assessed using visual analogue scale (VAS) at 0.5 h, 1 h, 4 h, 8 h, 12 h, 18 h, and 24 h. Where zero score corresponds to 'no pain' and 10 corresponds to the 'maximum' or 'worst pain'. Rescue analgesia in the form of inj. diclofenac sodium AQ 75 mg i.v. Total analgesic consumption in the first 24 h postoperatively and occurrence of nausea, vomiting and sedation were also recorded.

Results were reported as mean ± standard deviation (SD). Data were analysed by Student's t-test using Excel (Windows version 8). Results were considered statistically significant when P < 0.05.

RESULTS

The two groups were comparable in patient characteristics with respect to age and weight. The age of the patients in group B and group B+D with mean ± SD of 43.92 ± 12.63 years and 41.12 ± 11.02 years, respectively, and the weight of patients in group B and group B+D with mean ± SD were 59.5 ± 7.93 kg and 57.08 ± 8.15 kg, respectively (P > 0.05).

On analysing the VAS score at 0.5 h, 1 h, 4 h, 8 h, 12 h, 18 h, and 24 h. Postoperative mean VAS in both groups varied considerably within (between time) and between the groups. There was statistically significant difference in VAS score between the two groups after 12 h (P < 0.05) as shown in Table 1.

Table 1

Comparison of VAS score among the two groups

The duration of analgesia was comparatively higher in groups B+D (14.5 ± 1.86) than in group B (13.06 ± 1.09) and the mean number of rescue analgesia doses of group B (2.56 ± 0.20) was comparatively higher than group B+D (1.76 ± 0.16), which were statistically significant (P < 0.05) as shown in Table 2.

Table 2

Comparison of duration of analgesia and total rescue analgesic in two groups

Table 3 shows the postoperative changes in heart rate and MBP changes at different time interval. In our study, heart rate was less in groups B+D compared with group B during 30 min, 60 min, and 90 min after extubation that was statistically significant.

Table 3

Comparison of mean heart rate and mean blood pressure between the groups

In our study, out of 50 patients only 3 patients (6%) of group B and only 4 (8%) patients of groups B + D had postoperative nausea/vomiting, and 6 (12%) patients of group B and 2 (4%) patients of groups B+D had postoperative shoulder pain. However, hypotension, bradycardia and sedation were not seen in either group [Table 4].

Table 4

The table shows the adverse effects of two groups

DISCUSSION

Laparoscopic surgery, which is considered a minimally invasive surgery, is a modern surgical technique used for various surgeries. There are numerous arguments for a procedure-specific assessment of the evidence of analgesia treatment after laparoscopic surgery. Postoperative pain is reduced more speedily compared with open traditional surgeries, but effective analgesic treatment after laparoscopic surgeries have remained a clinical challenge. The patients undergoing laparoscopic surgery tend to expect a painless postoperative period because of common beliefs about this type of surgery. Pain is the main reason for staying overnight in the hospital on the day of surgery and pain is the dominant complaint and the primary reason for prolonged convalescence after laparoscopic surgery. So, it is an essential task to provide adequate postoperative analgesia. For that we can use various analgesics (opioids and nonopioids) via various routes, for example oral, intravenous, neuraxial blockade and intraperitoneal instillation. In addition, growing evidence suggests that the treatment of postoperative pain should be multimodal and opioid sparing to accelerate recovery and avoid potential side effects.

Pain is a highly personal experience a subjective sensation or emotion and it may be estimated by VAS score.[5] The visual analogue scale (VAS) is a 10-cm horizontal line labelled as 'no pain' at one end and 'worst pain imaginable' on the other end. The patient was asked to mark on this line where the intensity of pain lies. The distance from 'no pain' to the patient's mark numerically quantifies the pain. The VAS is a simple and efficient method that correlates well with other reliable method.[6]

The rationale for intraperitoneal administration of drugs for the treatment of the pain that follows laparoscopic surgery is that the small incisions at the abdominal wall cause visceral component of the pain and shoulder pain. With this in mind, many authors have tried to diminish pain via the peritoneal route. Intraperitoneal local anaesthetic is likely to blockade free afferent nerve endings in peritoneum. Systemic absorption of local anaesthetic from the peritoneal cavity may also play a part in reduced nociception although this would be expected to occur after any local anaesthetic technique.[7]

In the present study, postoperative VAS score was observed up to 24 h. There was statistically significant difference in VAS score between two groups after 12 h that was lower when dexmedetomidine added to bupivacaine. Similar results were observed with study done by Ahmed et al.[8] who compared the antinociceptive effect of dexmedetomidine or meperidine with bupivacaine to bupivacaine alone intraperitoneally after the laparoscopic gynaecological surgery found that intraperitoneal instillation of meperidine or dexmedetomidine in combination with bupivacaine significantly decreases VAS score.

Bakhamees et al.[9] evaluated the patients who received dexmedetomidine and found that they had less VAS score as compared to placebo in the postoperative period. Ahmed Mostafa et al.[9] observed that the patients who received intraperitoneal levobupivacaine instillation had profound postoperative analgesia.

Our study results also show that the duration of analgesia was higher and had less need of rescue analgesia in bupivacaine and dexmedetomidine group as compared to bupivacaine alone which were statistically significant.

Also Ahmed et al.[8] observed that intraperitoneal instillation of meperidine or dexmedetomidine in combination with bupivacaine significantly decreases total rescue analgesia requirement in postoperative period. Rajni Gupta et al.[11] compared postoperative analgesia with intraperitoneal bupivacaine and fentanyl with bupivacaine after laparoscopic surgery and observed that there is decrease total analgesics consumption in fentanyl with bupivacaine group.

Arain et al.[13] evaluated the efficacy of dexmedetomidine and morphine administered through intravenous route for postoperative analgesia after a major surgery. They found that dexmedetomidine patients group had better pain control compared to morphine patients group postoperatively. Bakhamees et al.[7] observed the patients who received dexmedetomidine had less postoperative analgesia demand (morphine) as compared to placebo in postoperative period.

In our study, there is decrease in heart rate in groups B+D due to the effect of dexmedetomidine on heart; our results were comparable with the study done by Bhattacharjee et al.[12] who compared the effects of dexmedetomidine on haemodynamics in patients undergoing laparoscopic cholecystectomy. They found postoperatively significant decrease in heart rate in dexmedetomidine group than saline group. Similar findings were observed in study done by Arain et al.[13] who studied the efficacy of dexmedetomidine and morphine for postoperative analgesia after a major surgery. They concluded that there is significant decrease in heart rate in the postanesthesia care unit (PACU) in dexmedetomidine group than morphine group.

Arain et al.[13] studied the efficacy of dexmedetomidine and morphine for postoperative analgesia after a major surgery. Bhattacharjee et al.[12] concluded that dexmetedomedine improves intra and post operative hemodynamic stability during laproscopic surgeries without prolongation of recovery and similar results were obtained by Bakhamees et al.9]

In our study, among group B patients, nausea/vomiting was found in 3 patients out of 50 patients and 4 patients out of 50 patients in groups B+D that is comparable to a study done by Bhakhamees et al.[9]

In our study, the incidence of shoulder pain was significantly low in groups B+D compared to group B. We found that in group B 6 patients out of 50 patients and in groups B+D, 2 patients out of 50 patients had postoperative shoulder pain that is comparable to the study done by Ahmed et al.[8]

CONCLUSION

Intraperitoneal instillation of dexmedetomidine with bupivacaine [50 mL bupivacaine 0.25% (125 mg) + 1 μg/kg dexmedetomidine] through ports produces prolonged duration of postoperative analgesia and less requirement of rescue analgesics in postoperative period compared to that with bupivacaine alone [intraperitoneal 50 mL bupivacaine 0.25% (125 mg)]. To conclude, dexmedetomidine seems to be an attractive alternative as adjuvant to bupivacaine in laparoscopic surgical procedure for postoperative pain relief management.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.