Post-operative analgesic technique in laparoscopic cholecystectomy : Comparison of local instillation with bupivacaine vs intravenous butorphanol vs intercostal nerve block with bupivacaine *

Background Present study was undertaken to evaluate an optimal analgesic technique which is safe, effective, feasible and devoid of side effects and complication for post-operative analgesia in patients undergoing laparoscopic cholecystectomy. The techniques under study were parenteral opioids or local intraperitoneal instillation and port-site infiltration with bupivacaine hydrochloride (HCL) or intercostal nerve block with bupivacaine HCl.


Introduction
Pain is "an unpleasant sensory and emotional experience associated with actual or potential tissue damage 1 .
The introduction of laparoscopic cholecystectomy by Mouret in 1987, Dubois in 1988 and McKernan / Saye in the same year has opened up a new dimension in minimally invasive surgery.A number of reports have highlighted its advantages of reduced post operative pain, reduced hospital stay, decreased morbidity, earlier return to work and cost effectiveness as compared to conventional cholecystectomy 2 .Interestingly, the type of pain after laparoscopy differs considerably from that seen after laparotomy.Laparotomy results mainly in parietal pain(abdominal wall), whereas patients complain more of visceral pain after laparoscopy 3 .Finally, shoulder pain secondary to diaphragmatic irritation as a result of CO 2 pneumoperitoneum is a frequent postoperative observation after laparoscopy 4 .
Inadequately treated pain may lead to splinting, loss of sighing and decrease of vital capacity and these may contribute to post-operative pulmonary morbidity 5 .Although thought to result in less post-operative pain, recent studies have shown that patients may experience considerable pain after laparoscopic cholecystectomy.Being a relatively new procedure, there is no general agreement on effective post-operative pain control 6 .
We performed this study to compare and evaluate the duration and quality of three postoperative analgesic techniques in laparoscopic cholecystectomy: intraperitoneal (IP) instillation and port site infiltration with bupivacaine, intercostal nerve block with bupivacaine (ICNB) (T 5 -T 11 )and i.v.butorphanol(iv BUT).

Patients and Methods
After hospital ethics committee approval and informed written consent from patients a total of 100 ASA Grade I and II patients of either sex between the age group 20-60 years undergoing laparoscopic cholecystectomy under GA were randomly allocated into four groups of 25 patients each.Patients with bleeding disorders, systemic diseases, acute cholecystitis, hypersensitivity to local anaesthetics (LA), opioids and non-steroidal anti-inflammatory drugs, mental disorder and patients converted to conventional cholecystectomy by surgeons due to any reason were not included in the study.
Patients were prepared by overnight fasting and premedicated with alprazolam 0.25mg per oral on previous night.On the morning of surgery they were premedicated with alprazolam 0.25 mg per oral, glycopyrrolate 0.2mg and diclofenac sodium 75 mg i.m. 45 minutes before surgery.
In the operation theatre, i.v line was established; patient was catheterised and connected to monitors to measure: Pulse Rate (PR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Blood Pressure (MBP), Oxygen Saturation (SpO 2 ), and ECG.Patients were given i.v.granisetron 2mgas an antiemetic.Induction was carried with 2 mg/kg propofol and endotracheal intubation was facilitated using vecuronium bromide 0.1 mg/kg body weight.Anaesthesia was maintained using N 2 O in O 2 (66%: 33%) along with isoflurane 0.5% and incremental doses of vecuronium bromide as and when required.A nasogastric tube was introduced and the laparoscopic procedure was undertaken in a standard fashion.Intraabdominal pressure was maintained between 10-12 mmHg.
The residual muscle relaxation was reversed at the end of surgery with neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg body weight.The nasogastric tube was removed after recovery from anaesthesia.
At the end of laparoscopic cholecystectomy patients were randomly allocated to 4 groups.
Group I (IP): Received local intraperitoneal instillation with 15 ml of 0.375 % bupivacaine and port site infiltration with 10 ml of 0.25 % bupivacaine.

Group IV(CONT):
Received analgesia as and when needed depending on VAS.

Parameters monitored
Post-operative pain was assessed using VAS: consisting of 10 cm scale from 0 (no pain) to 10 (worst imaginable pain).Shoulder pain: recorded on a 5 point scale.1-No pain 2-Discomfort in shoulder but no pain 3-Light pain (no analgesia required) 4-Moderate pain (analgesia required) 5-Severe pain (analgesia and sedation required) Rescue analgesic was diclofenac sodium 75 mg i.m. when VAS > 6.The degree of sedation was assessed by using Ramsay sedation scale.Haemodynamic variables and side effects of drugs were also observed.All the above parameters were assessed at 0, 1, 2, 4, 8, 12 and 24 hrs.
A sample size of approximately 22 per group was needed to demonstrate a difference of 25% in VAS considering an α of 95% (.05) and power of the study as 80%.Data was analyzed statistically using ANOVA, t-test, Borferronis ttest.P valve < 0.05 was taken as significant.

Results
Mean post-operative (Ramsay) sedation score at 0, l, 2, 4, 8, 12, 16 and 24hrs in group I(IP), group II(ICNB), group III(iv BUT) and group IV(CONT) is 2, which is comparable in all the four groups and statistically insignificant (p value> 0.05).The difference in VAS in all the four groups was statistically highly significant at 1hr, 16hrs and 24hrs (p<0.005); and was significant at 0hr, 3hrs, 4hrs, 8hrs and 12 hrs.(p<0.05).The duration of analgesia was maximum in group II and least in group IV which was highly significant (p<0.0005).

Discussion:
The difference in VAS in group I (IP), group II (ICNB), group III (i.v.BUT), and group IV (CONT) was found to be statistically highly significant at 1, 16 and 24hrs (P value < 0.005) and significant at 0, 2, 4, 8 and 12hrs (P value < 0.05)(Table 2).In our study, the pain relief in group I was noted up to 6.54 ± 4.63hrs.i.e VAS < 6 post-operatively(P value = 0.0000)(Table 3).These findings are consistent with the findings of Neerja Bhardhwaj et al, who used 20 ml of 0.5% bupivacaine with 1: 200000 adrenaline 6 .They noted pain relief up to 8hrs, and less shoulder pain and analgesic requirement post-operatively.
Narchi et al also found that post-operative pain relief by intraperitoneal LA instillation lasted for 48hrs in patients undergoing diagnostic laparoscopy 7 .D. J. Alexander et al demonstrated that direct periportal injection of bupivacaine at the level of parietal peritoneum reduces pain 8 .
Our study is in contrast to the studies by Rademaker et al and Joris et al using 20 ml of 0.25 % bupivacaine or 0.5 % lignocaine and 80ml of 0.125 % bupivacaine with adrenaline respectively, who failed to demonstrate any reduction in post-operative pain 9,10 .Scheinin et al also found no relief of pain after administration of 100 ml of either 0.15 % plain bupivacaine alone or with adrenaline 11 .While Chundrigar et al showed pain relief only up to two hours with intraperitoneal administration of 0.25 % bupivacaine 12 .All these negative results could be related to the lower concentrations and lower volumes of local anaesthetic used by them as compared to our study which has given good results.
Group II patients experienced pain relief for up to 9.48 ± 4.44hrs post-operatively (P value = 0.0000)(table .3) which is in conformation with the study by Moore et al and Nunn and Slavin who demonstrated the mean duration of right abdominal analgesia of 12.3hrs postoperatively 13,14 .Group III patients had pain relief up to 5.04 ±1.73hrs post-operatively (P Value = 0.0000) (table 3).Analgesia obtained was good but of shorter duration, which is consistent with the study conducted by Galloway et al 15 .Patients belonging to group IV noted mean duration of pain free period of 1.5 ±1.60hrs which is highly significant (p value =0.0000) (table 3).
In our study patients received rescue analgesia when VAS ≥ 6, which consisted of diclofenac sodium 75 mg i.m.The mean number of rescue analgesic doses required in group I were 1.4 ± 0.7 (P value = 0.00)(table 4), which is in concordance with the study of Neerja Bhardwaj et al 6 .In group II were 0.88 ± 0.52 (P value = 0.00)(table.4), thus going in favour of studies by Moore et al 13 , Nunn and Slavin 14 .In group III the mean number of rescue analgesic doses required were 2.08 ± 0.57 (P value = 0.00) (Table 4), supporting the studies done by Galloway et al 15 and Tavakoli et al 16 .Group IV patients received rescue analgesia when VAS ≥ 6 and the mean number of rescue analgesic dose required were 1.88±0.52(p value =0.00).Thus rescue analgesic requirement was more in groups III and IV as compared to group I and was least in group II(table4 and 6).Intensity and severity of shoulder pain was statistically insignificant (P value > 0.05) in all the four groups (Table 4).
Haemodynamic variables were found to be statistically insignificant in all the groups 6,13 .
Side-effects like nausea and vomiting were slightly more in patients in group III which were statistically insignificant (Table 7).Disadvantage of nausea and vomiting associated with opioids are avoided by intercostal nerve block 17 .No severe systemic toxic reactions or pneumothorax have resulted from intercostal block in our series 17 .
From the results we derived that i.v.butorphanol produced excellent analgesia of shorter duration (5.04 ± 1.73hrs), with slightly more incidence of nausea and vomiting which was statistically insignificant; intraperitoneal instillation and port-site infiltration with bupivacaine provided comparable analgesia but of somewhat longer duration (6.54 ± 4.63hrs) with no major side effect; intercostal nerve block produced safe and effective analgesia of longer duration (9.48 + 4.44hrs) amongst the four groups with almost negligible side effects.

Table 1 :
Demographic variables of patients

Table 2 :
Mean post-operative VAS at different time intervals

Table 3 :
Mean post-operative duration of analgesia (in hours)

Table 4 :
Number of rescue (analgesic) doses required in 24 hours post-operatively

Table 5 :
Number of patients having shoulder pain 24 hours post-operatively

Table 6 :
Inter group comparison of mean number of rescue (analgesic) doses required in 24 hours post operatively.