Intraperitoneal Levobupivacaine Alone or with Dexmedetomidine for Postoperative Analgesia after Laparoscopic Cholecystectomy.

BACKGROUND AND AIMS: Local anesthetic injection in the peritoneal cavity decreases intensity of postoperative pain after laparoscopic surgeries. We compared adding dexmedetomidine to intraperitoneal levobupivacaine in patients undergoing laparoscopic cholecystectomy.
METHODS: A total of 105 patients were included in this prospective, double-blinded, randomized study. Patients were randomly divided into three equal sized (n = 35) study groups. Group C patients received intraperitoneal 40 ml normal saline as controlled group. Group L was given 40 ml 0.25% levobupivacaine. Group LD received 40 ml 0.25% levobupivacaine + dexmedetomidine 1 μg/kg. The degree of postoperative pain was measured by visual analog scale (VAS) score. The time of first analgesic demand was recorded and also total dose of painkiller in the first 24 h and postoperative complications were collected. SPSS version 16 was used for statistical analysis. P < 0.05 was considered statistically significant.
RESULTS: Postoperative VAS at different time intervals was significantly lower, time to the first demand of painkiller (min) was longer (30.2 ± 14.4, 45.9 ± 20.1, and 56.5 ± 13.2), and total painkiller consumption (mg) was lower (203.5 ± 42.9, 117.8 ± 63.7, and 46.3 ± 41.3) in Group LD than Group L than Group C.
CONCLUSION: Adding dexmedetomidine to intraperitoneal levobupivacaine is superior to and gives better results than levobupivacaine alone in patients undergoing laparoscopic cholecystectomy.

INTRODUCTION

Laparoscopic cholecystectomy recently is the method of choice for treating gallstones.[1] Advantages over open procedures are less bleeding, better cosmosis, less postoperative pain, and shorter postoperative stay.[2]

Causes of postoperative pain include intra-abdominal cavity stretch,[3] inflammation of the peritoneum, and irritation of diaphragm by carbon-dioxide residue in the abdominal cavity.[4]

Intraperitoneal instillation of different drugs decreases postoperative pain after laparoscopy such as local anesthetic drugs alone[5] or with opioids[6] and α2 agonists drugs such as clonidine[7] and dexmedetomidine.[8]

Our aim was to find the effects of adding dexmedetomidine to intraperitoneal levobupivacaine in patients undergoing laparoscopic cholecystectomy.

We hypothesized that adding dexmedetomidine to intraperitoneal levobupivacaine will increase its analgesic effects regarding degree and duration of analgesia in patients undergoing laparoscopic cholecystectomy.

METHODS

After getting approval from the Institutional Ethics Committee, Mansoura University, and obtaining written informed consent from patients before surgery, 105 patients with American Society of Anesthesiologists (ASA) physical status classes I and II of either sexes, aged between 21 and 50 years, were included in the study. This prospective, randomized, double-blind controlled study was conducted between February 2016 and September 2016. Exclusion criteria included allergy to local anesthetics, severe cardiac diseases, pulmonary dysfunctions, neurological defects, and in whom abdominal drain was put. No premedication was used. After patients came to surgical theater, an 18-gauge cannula (IV) was inserted intravenously and crystalloid was given in a dose of 6 ml/kg/h intraoperatively; routine intraoperative monitoring including 5-lead electrocardiography, noninvasive blood pressure measuring, and pulse oximetry (SpO2) was started, with baseline values being recorded. Preoxygenation with 100% oxygen (O2) was started for 3 min. Anesthesia was induced using IV fentanyl 1 μg/kg and atracurium 0.5 mg/kg for muscle relaxation and then propofol 2.0–2.5 mg/kg for intubation using an appropriately sized cuffed endotracheal tube lubricated with lidocaine jelly 2%. Anesthesia was maintained with 40% O2 and 60% air with isoflurane in a minimum alveolar concentration of 1%. Intermittent injections of atracurium were used for muscle relaxation. Mechanical ventilation was maintained to have an end-tidal carbon dioxide level around 35 mmHg. Hypotension/hypertension was considered when there is a change in systolic pressure >20% from the baseline value and also bradycardia/tachycardia was considered if there is a decrease/increase in heart rate >20% from the baseline value. Reverse Trendelenburg's position of 15°–20° degree was used during surgery, intra-abdominal pressure was adjusted between 12 and 14 mmHg, and manual pressure on the abdomen was used to remove residual CO2. Patients were randomly classified to one of three study groups using a randomization table: Group C (n = 35), intraperitoneal 40 ml saline; Group L (n = 35), intraperitoneal 40 ml 0.25% levobupivacaine; and Group LD (n = 35), intraperitoneal 40 ml 0.25% levobupivacaine + dexmedetomidine 1 μg/kg. An anesthesiologist not involved in the study prepared the applied drugs. Anesthesiologist who observed the patients and surgeon were unaware of the study group until the end of the study. Before the end of the surgery, the drugs were injected intraperitoneally by the operator before trocar removal in head-down position in bladder bed. Neuromuscular relaxant was reversed by neostigmine 0.04 mg/kg and atropine 0.02 mg/kg followed by tracheal extubation, and then the patient was sent to postanesthesia care unit and stayed for 1 h after operation. The primary outcome was to measure pain intensity using visual analog scale (VAS) score (VAS score 0 – no pain and VAS score 10 – worst possible pain). The secondary outcome was to compare time to the first command of analgesics in the postoperative stay, total dose of nonsteroidal analgesics used in 24 h period (postoperative), and any side effects. The intensity of postoperative pain was recorded for all the patients using VAS score at 0.5, 1, 2, 4, 6, 12, and 24 h after surgery during rest and movement. All the study patients were instructed about the use of the VAS score before induction of anesthesia. Patients who reported VAS ≥ 3 were given diclofenac 75 mg intramuscular.

Sample size

We found that approximately 30 patients in each group are enough to get a power of 0.8 to detect a 15% or more decrease in pain intensity and increase in duration of postoperative analgesia in the dexmedetomidine group.

Statistical analysis

Data were collected and SPSS 16 (SPSS Inc. Released 2007. SPSS for Windows, Version 16. Chicago, SPSS Inc.) was used for analysis. Continuous variables were expressed as mean ± standard, and categorical variables presented as number and percentages (%). One-way ANOVA test was used for comparing continuous variables with normality, Kruskal–Wallis test was used to compare continuous nonnormal variables and ordinal variables, and Chi-square was used for categorical data. P < 0.05 was considered statistically significant.

RESULTS

Patient randomization and study design

One hundred and twelve patients began the study, 7 patients were excluded during operative procedure due to the need of surgical drain, and 105 patients completed the study; the sample size was limited to 105 patients.

There were no significant differences between groups considering age, sex, and weight and ASA classification, time of surgery, and anesthesia time [Table 1].

Table 1

Patients’ characteristic data (mean±standard deviation) or number

Postoperative VAS scores were statistically significantly lower in Group LD than Group C and Group L [Table 2] at different times.

Table 2

Postoperative pain (data are in mean±standard deviation)

The dose of diclofenac was lower in Group LD compared to Group C and Group L (P < 0.001), and first time to need diclofenac was significantly longer in Group LD than Group L than group C [Table 3].

Table 3

Analgesic requirements (mean±standard deviation) in studied groups

Vomiting was not statistically significant in the study groups, while shoulder pain was higher in controlled group (10) patients compared to Group L and Group LD (3 and 2, respectively) patients [Table 4].

Table 4

Postoperative adverse/side effects (%) in the studied groups

DISCUSSION

Postcholecystectomy pain includes three types, visceral, parietal, and shoulder pain with varying degrees in intensity, latency, and duration.[3] Previous studies[910] suggested that parietal pain is predominant; other studies reported that visceral pain is predominant due to small incisions and surgical trauma and tissue destruction in viscera are more.[111213]

Opioid drugs, nonsteroidal anti-inflammatory drugs, or local anesthetics were used to reduce pain after laparoscopic surgeries[141516] with its adverse effects such as respiratory depression and nausea. Intraperitoneal application of local anesthetic drugs becomes an important way to decrease postoperative pain, nausea, vomiting, and decreased cost.[1718] In laparoscopy, due to CO2 gas and high intra-abdominal pressure, peritoneal inflammation and nerve injury occur.[14] Hence, we chose intraperitoneal injection of drugs to block the visceral stimulation.

Dexmedetomidine has antinociceptive effects at dorsal root neurons, decreasing substance P release, and stimulating the inhibitory G protein, which increases potassium channel conductivity.[19]

In our study, postoperative VAS scores were lower in Group DL than Group L than in Group C; these results are in agreement with Karaman et al. who reported the analgesic effects of intraperitoneal levobupivacaine for laparoscopic cholecystectomy and found that it is an effective method for decreasing pain after laparoscopic cholecystectomy and reducing antiemetic drug taking.[20]

Similarly, Ahmed et al. found that adding meperidine or dexmedetomidine to intraperitoneal bupivacaine 0.25% significantly decreased analgesic needs and shoulder pain in laparoscopic gynecological surgeries.[8]

First time for taking diclofenac was significantly lower in Group LD compared to Group L (P < 0.001) and Group C (P = 0.025). Higher amounts are needed in Group C as compared to Group L or Group DL (P < 0.001) and this is also reported by Ahmed et al.[8]

Regarding vomiting, no statistically significant difference was recorded between groups, while shoulder pain was higher in Group C compared to other groups. Shukla et al. also noted less shoulder pain in intraperitoneal bupivacaine and dexmedetomidine groups following laparoscopic cholecystectomy.[21]

Shoulder pain caused by phrenic nerve neuropraxia, diaphragmatic fibers distension as a result of pneumoperitoneum and traumatic stimulation.[22] Levobupivacaine injection in subdiaphragmatic area may block diaphragmatic peritoneal stimulation. In the previous studies, intraperitoneal local anesthetics application reduced shoulder pain. Gharaibeh and Al-Jaberi[23] used intraperitoneal 0.25% bupivacaine in laparoscopic cholecystectomy and found reduction in frequency of shoulder pain. Furthermore, Louizos et al.[24] found that intraperitoneal levobupivacaine application decreased right shoulder pain after laparoscopic cholecystectomy. Similarly, right shoulder pain was less in levobupivacaine group compared to the control group.

Limitation of this clinical study is that postoperative pain is a subjective method and difficult to be assessed when comparing various methods to decrease it.

CONCLUSION

Adding dexmedetomidine 1 μg/kg to intraperitoneal levobupivacaine 0.25% in laparoscopic cholecystectomy decreases the postoperative analgesic needs in postoperative period as compared to levobupivacaine 0.25% alone and improves quality and duration of analgesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.