Comparative Study of Postoperative Pain Relief Using Preincisional Versus Postincisional Infiltration With 0.25% Bupivacaine in Abdominal Hysterectomy Under General Anesthesia.

Background and Aims: Hysterectomy, probably the most common non-pregnancy related surgery performed in gynaecology, is associated with moderate to severe post-operative pain. Wound infiltration with local anaesthetic agent reduces the transmission of pain from the wound, in addition, local inflammatory response to the injury is also suppressed. The infiltration of local anaesthesia can be done either pre- or post-operatively. The present study was designed to determine the efficacy of pre-incisional infiltration versus post-incisional infiltration with 0.25% Bupivacaine in providing post-operative pain relief in patients undergoing abdominal hysterectomy.
Methods: In Prospective Interventional Randomised study, 90 female patients posted for elective abdominal hysterectomy under general anaesthesia were randomly allocated into three equal groups of 30 patients each. Group I: Patients receiving subcutaneous infiltration with 40 mL of 0.25% Bupivacaine 5 mins before skin incision. Group II: Patients receiving subcutaneous infiltration of surgical area with 40 mL of 0.25% Bupivacaine at end of surgery (after peritoneal closure). Group III Control Group: Patients receiving no local anaesthetic infiltration. Observations were made for the duration of effective analgesia from end of the surgery until the first use of rescue analgesic along with the frequency and cumulative amount of rescue analgesics in 24 hours.
Results: We found that at baseline, pain score of patients in Group III (3.87±1.17) was maximum followed by that in Group I (2.57±0.90) and minimum in Group II (2.20±0.61). Requirement of first analgesia was earliest in Group III (79.50±23.90 minutes) followed by Group I (136.83±13.16 minutes) and last in Group II (146.17±12.78 minutes), in addition, cumulative dose of analgesia was required by patients in Group III (152.50±36.76 mg) followed by that in Group I (132.50±37.80 mg) and minimum by that in Group II (115.00±38.06 mg).
Conclusion: Subcutaneous infiltration of Bupivacaine either pre-incisional or post-incisional, helped to reduce the immediate post-operative pain intensity, delayed the first rescue analgesic requirement, reduced the post-operative dose and frequency of rescue analgesia. However, post-incisional intervention had an edge over pre-incisional intervention. Copyright:

INTRODUCTION

Hysterectomy is currently one of the most common surgical procedure in gynecology[1] and probably the most common nonpregnancy-related surgery performed in gynecology.[23] Abdominal hysterectomy (AH) is associated with moderate to severe postoperative pain which is usually of two types: a continuous dull nauseating ache of visceral origin and the other is a sharper somatic pain.[4] Traditionally, postoperative pain management is done using opioids administered systemically using patient-controlled intravenous (i.v.) analgesia, or neuroaxially through epidural or spinal injections. Wound infiltration with local anesthetic agents has gained popularity in a variety of procedures[5678] which is simple, safe and low-cost technique. Due to local application, transmission of pain from the wound is reduced and the local inflammatory response to the injury is suppressed. The infiltration of local anesthesia can be done at two possible times, either preoperatively or postoperatively. Bupivacaine, one of the most common anesthetic agents used for gynecological surgeries, is a long-acting amide, metabolized in the liver. Its unique property of wide differential sensory and motor blockade makes it a choice for postoperative pain relief. The present study was designed to determine the efficacy of preincisional infiltration versus postincisional infiltration with 0.25% Bupivacaine in providing postoperative pain relief in patients undergoing AH.

METHODS

The present study was a prospective interventional randomized study, carried out in a tertiary care medical college in Lucknow, India. Our clinical research was standardized following ethical principles of medical research involving human subjects according to the Helsinki Declaration 2013. After obtaining clearance from Institutional Ethical Committee, 90 female patients of 40–65 years of age ASA PS Classes I and II posted for elective AH under general anesthesia were included in the study and randomly allocated into three equal groups of 30 patients each. Group I: Patients receiving subcutaneous infiltration with 40 mL of 0.25% Bupivacaine 15 min before skin incision. Group II: Patients receiving subcutaneous infiltration of surgical area with 40 mL of 0.25% Bupivacaine at end of surgery (after peritoneal closure). Group III (Control Group): Patients receiving no local anesthetic infiltration. Patients with previous respiratory disease, on regular medication with nonsteroidal anti-inflammatory drugs or opioids, obesity, ovarian cancer, known allergy or sensitivity to the study drug, duration of surgery >2 h, and a patient who refuse to give consent for the study were excluded. All patients were intubated with injection midazolam 0.03 mg.kg−1, injection fentany l 2 ug.kg−1, injection propofol 2 mg.kg−1 and vecuronium 0.1 mg.kg−1 and maintained with isoflurane 1%–1.5 vol% and N2O: O2 (60%:40%) and vecuronium 0.02 mg.kg−1 as needed. Heart rate (HR), noninvasive blood pressure, respiratory rate (RR), peripheral oxygen saturation (SpO2) and end-tidal CO2 were monitored throughout the surgery. One gram i.v. Paracetamol was administered 30 min prior to closure. The study drug was administered as per the protocol of the study by the operating surgeon at appropriate timings: preincisional or postincisional. At the end of the surgery, muscle paralysis was reversed with i.v. Neostigmine (50 μg.kg−1) and Glycopyrrolate (10 μg.kg−1).

Following recovery from anesthesia, patients were shifted to postoperative ward. HR, Noninvasive blood pressure, RR, and peripheral oxygen saturation were recorded at regular intervals and pain was assessed at the end of the surgery (baseline) and 2, 4, 6, 8, 10, 12, 16, 20, and 24 h thereafter. The duration of effective analgesia was measured from the end of the surgery until the first use of the rescue analgesic. The number of rescue analgesics and cumulative dose in 24 h were also recorded. Pain was assessed using 10-point Visual Analog Scale (VAS). Adverse effects such as nausea, vomiting were also documented and managed accordingly.

Statistical analysis

The statistical analysis was done using SPSS 23.0 VERSION (Chicago, inc., USA) statistical Analysis Software. The values were represented in Number (%) and mean ± standard deviation. The analysis of variance test was used to compare the within group and between-group variances. To compare the change in a parameter at two different time intervals paired t-test was used. Mann–Whitney U-test was used for nonparametric data, and Chi-square test was used for categorical outcome. P < 0.05 considered statistically significant. The sample size was calculated using the formula:[9]

where,σ1 = 84

σ2 = 117.6

d = mean (ς1, ς2)

α = Type I error (5%)

β = Type II error (10%)

Power of study = 90%

Data loss = 10%

Sample Size comes out to be

n = 30 each group.

RESULTS

All the groups were equal in terms of age, weight, and ASA physical status class.

Differences in HR, Systolic and Diastolic blood pressure among patients in the above three groups were not found to be statistically significant at any of the time intervals. At the baseline, pain score of patients in Group III (3.87 ± 1.17) was maximum followed by that in Group I (2.57 ± 0.90) and minimum in Group II (2.20 ± 0.61). The difference in VAS among patients in Group I, II and III was found to be statistically significant [Table 1]. On comparing between Groups at baseline [Table 2], differences were not found to be statistically significant between-study Groups (P = 0.059). However, when study groups were compared with the control group separately, a significant difference was noticed indicating that Pain score of Group III > Group I ≈ Group II.

Table 1

Intergroup comparison of pain score (Visual Analog Scale) at different time intervals

	Mean±SD			Kruskal-Wallis H test
	Group I (n=30)	Group II (n=30)	Group III (n=30)	H	P
Baseline	2.57±0.90	2.20±0.61	3.87±1.17	34.453	<0.001
2 h	4.60±0.93	4.67±0.84	5.00±0.98	5.002	0.082
4 h	4.33±0.48	4.33±0.71	3.53±0.97	16.200	<0.001
6 h	3.93±0.37	3.40±0.93	3.80±1.24	5.178	0.075
8 h	4.13±0.63	3.80±1.56	4.23±1.57	1.148	0.563
10 h	4.23±0.73	4.37±1.19	3.70±0.79	8.282	0.016
12 h	4.00±0.64	3.93±0.98	4.40±1.33	3.452	0.178
16 h	3.00±1.02	3.13±1.01	3.53±1.14	3.494	0.174
20 h	1.60±0.97	2.47±0.86	2.60±1.50	12.499	0.002
24 h	1.330.96	1.07±1.01	1.80±1.21	5.928	0.052

SD=Standard deviation

Table 2

Between group comparison of pain score (Mann-Whitney U test)

	Group I versus Group II		Group I versus Group III		Group II versus Group III
	Z	P	Z	P	Z	P
Baseline	1.885	0.059	4.163	0.003	5.383	<0.001
2 h	0.573	0.567	2.002	0.045	1.724	0.085
4 h	0.176	0.861	3.551	<0.001	3.415	0.001
6 h	2.748	0.006	0.640	0.522	1.249	0.212
8 h	0.693	0.488	0.366	0.715	1.037	0.300
10 h	0.442	0.658	2.677	0.007	2.434	0.015
12 h	0.698	0.485	1.380	0.167	1.593	0.111
16 h	0.513	0.608	1.788	0.074	1.328	0.184
20 h	3.326	0.001	2.827	0.005	0.047	0.963
24 h	1.045	0.296	1.499	0.134	2.326	0.020

Rescue analgesia was given to patients who manifested a pain score >4, following which a significant decline in pain score was observed. Change in pain score was not analyzed thereafter as it was because of external factors (rescue analgesia).

The requirement of first analgesia [Table 3] was earliest in Group III (79.50 ± 23.90 min) followed by Group I (136.83 ± 13.16 min) and last in Group II (146.17 ± 12.78 min). This intergroup comparison of time for first analgesia among patients of Group I, Group II, and Group III was found to be statistically significant (P < 0.001). While comparing time for first analgesia between groups [Table 4], the difference between study groups was not found to be statistically significant (P = 0.100). However, when the study group was compared with control group, it was highly significant (P < 0.001). Hence, the requirement of rescue analgesia was: Group III < Group I ≈ Group II.

Table 3

Intergroup comparison of time for first analgesia requirement (minutes)

Group	n	Minimum	Maximum	Median	Mean±SD
Group I	30	115	170	140.00	136.83±13.16
Group II	30	115	170	147.50	146.17±12.78
Group III	30	30	120	90.00	79.50±23.90
Total	90	30	170	130.00	120.83±34.27

F=129.193; P<0.001. SD=Standard deviation

Table 4

Between-group comparison of time for first analgesia requirement

	Mean difference	SE	P
Group I versus Group II	9.33	4.49	0.100
Group I versus Group III	57.33	4.49	<0.001
Group II versus Group III	66.67	4.49	<0.001

SE=Standard error

Cumulative dose of analgesia was required by patients in Group III (152.50 ± 36.76 mg) followed by that in Group I (132.50 ± 37.80 mg) and minimum by that in Group II (115.00 ± 38.06 mg). Intergroup difference in total dose of analgesia among patients in above three groups was found to be statistically significant (P < 0.001) [Table 5]. Between-group difference in total dose of analgesia was found to be statistically significant only between Group II and Group III (P < 0.001). Order of dose of analgesia was: Group III > Group II ≈ Group I.

Table 5

Intergroup comparison of total dose of analgesia required (mg)

Group	n	Minimum	Maximum	Median	Mean±SD
Group I	30	75	225	150	132.50±37.80
Group II	30	75	125	150	115.00±38.06
Group III	30	75	225	150	152.50±36.76
Total	90	75	225	150	133.33±40.18

F=7.494, P<0.001. SD=Standard deviation

The proportion of patients requiring rescue analgesia only once was significantly higher among Group II and Group I as compared to Group III (33.33% vs. 26.67% and 6.67%) while proportion of patients in Group III was higher as compared to Group II and Group I requiring rescue analgesia for 2 times (80.00% vs. 66.67% and 70.00%) and 3 times (13.33% vs. 3.33% and 0.00%). Difference in number of rescue analgesics among patients of the above three groups was found to be statistically significant [Table 6].

Table 6

Intergroup comparison of frequency of rescue analgesia

Number of times rescue analgesia required	Total (n=90)	Group I (n=30)	Group II (n=30)	Group III (n=30)
1	25	8 (26.67)	10 (33.33)	2 (6.67)
2	60	21 (70.00)	20 (66.67)	24 (80.00)
3	5	1 (3.33)	0	4 (13.33)

χ2=13.780 (df=6), P<0.001

DISCUSSION

Postoperative pain is one of the major concerns in AH procedures. The use of local anesthetics during, or immediately after the procedure is suggested ways to reduce the burden of pain. However, there is debate regarding the timing of preemptive analgesic administration. In view of considerable onset time of different local analgesics, it is often proposed that the preemptive local analgesia should be administered even prior to making an incision, proponents of this viewpoint are of the opinion that the concept of preemptive or preincisional analgesia focuses on the prevention of central sensitization triggered by surgical incision. However, other factors have been advocated to exaggerate acute and long-term postoperative pain as a result of central sensitization namely, noxious intraoperative stimuli as retraction, postoperative inflammatory processes, and ectopic neural activity.[10] There are some studies that propose that preincisional analgesic infiltration can delay the first analgesic requirement in the postoperative period.[1112] With this background the present study was carried out with an aim to evaluate and compare the postoperative pain relief in AH patient under general anesthesia after preincisional versus postincisional infiltration of surgical area with Bupivacaine. The dose selection of Bupivacaine was done keeping in view the previous studies that have reported up to 50 mL of 0.25% to 0.375% Bupivacaine infused subcutaneously to be safe and effective in the management of postoperative pain in AH or other major abdominal surgery cases.[1314] With respect to physical characteristics of patients, all the three groups were comparable statistically (P > 0.05) for age, weight, and ASA physical status class. Although subcutaneous intra-incisional Bupivacaine administration has been reported to have no adverse hemodynamic effect[13141516] in total AH or other major abdominal surgeries or other procedures,[1718] however, in order to doubly ensure the same we measured the HR and blood pressure (Systolic blood pressure, diastolic blood pressure) and did not find a significant intergroup difference (P > 0.05), thus showing that hemodynamics was not affected by interventional drug in either of two study groups and were comparable to control group. With respect to pain scores, it was seen that at baseline, both the study Groups (I and II) had significantly (P < 0.001) lower pain score (2.57 ± 0.09 and 2.20 ± 0.61, respectively) as compared to that in control group (3.87 ± 1.17), thus signifying that both preincision and postincision Bupivacaine group exercised better pain control as compared to control group where no intraincisional anesthetic was given. At 2 h, pre- and postincisional Bupivacaine groups were comparable to the control group (P = 0.082), however, one must not forget the fact that by the end of 2 h all the patients in control group had taken rescue analgesic (79.50 ± 23.90 min) as compared to the two study groups where the first rescue analgesic need in any patient was not before 115 min and mean pain scores in control group were reflective of analgesic effect of rescue analgesia itself. However, at 4 h, both the study groups had significantly higher pain score (4.33 ± 0.48 and 4.33 ± 0.71) as compared to the control group (3.53 ± with P < 0.001, but this relationship was somewhat confounded by the fact that by the end of 4 h, all the patients in all the three groups had received rescue analgesic hence subsequent VAS assessments were confounded by the effect of rescue analgesic and do not hold much value. As far as mean time taken for first rescue analgesic is concerned, it was minimum in control group (79.50 ± 23.90 min) followed by preincisional group (136.83 ± 13.16 min) and maximum in postincisional group (146.17 ± 12.78 min). Thus, the control group had analgesic need 66.667 min earlier as compared to postincision group and 57.33 min earlier as compared to preincision group. This difference was significant statistically (P < 0.001). The difference between pre and postincisional group was only 9.33 min which was not significant statistically (P = 0.100). Hence, the findings showed that subcutaneous intra-incisional analgesic infiltration, irrespective of time (preincision or postincision) provided effective pain control, prolonging the postoperative rescue analgesic need. As far as cumulative dose of postoperative rescue analgesia was concerned, although preincisional group reduced it by a mean dose of 20 mg as compared to control group yet this difference was not significant statistically (P = 0.104). However, the difference in dosage of rescue analgesic as compared to control was significantly lower in postincisional group that reduced its mean requirement by 37.5 mg (P < 0.001). While comparing with preincisional group, postincisional group reduced analgesic dose by a mean of 17.5 mg yet this difference was not significant statistically (P = 0.174). The present study also revealed that the number of patients requiring only one rescue analgesic dose was higher in both the study groups as compared to control group. Furthermore, the number of patients requiring more than one dose of rescue analgesic was 93.33% in control group as compared to 73.33% in preincisional and 66.67% in postincisional Bupivacaine group. There was only 1 patient in preincisional and no patient in postincisional group requiring 3 analgesic dosages as compared to 4 patients in control group. Preincisional subcutaneous Bupivacaine delayed the rescue analgesic need and reduced the frequency of rescue analgesia significantly as compared to control but did not show any significant difference in mean rescue analgesic requirement, showing that preincisional subcutaneous Bupivacaine was beneficial in prolonging the analgesic need and frequency of rescue analgesic. The use of postincisional Bupivacaine was successful in not only prolonging the analgesic effect as well as reducing analgesic need as compared to control group. Similar to the present study, Ng et al.[13] in their study also found that 50 mL of postincisional 0.25% Bupivacaine in combination with 5 μg.mL−1 epinephrine not only delayed the first rescue analgesic need but also reduced the amount of postoperative analgesia in patients who underwent AH. In another study, Atashkhoii et al.[14] also observed significantly lower pain scores in cases who received postincisional 45 mL of Bupivacaine 0.35% as compared to 45 mL of normal saline among patients undergoing AH. In their study, first rescue analgesic need in postincisional Bupivacaine group was 5.87 h as compared to 1.35 h in control group. However, in our study, the first rescue analgesic need was slightly higher in control group as compared to their study (1.9 h as compared to 1.35 h) and in postincisional group, it was lower as compared to their study (2.5 h as compared to 5.87 h). The reason for this difference could be owing to higher dosage as well as concentration of Bupivacaine used in their study.

Contrary to findings of the present study, that found postincisional Bupivacaine to be the best modality, in their study among elective cholecystectomy patients found preincisional Bupivacaine to be better than postincisional and control group for prolonging the analgesic effect. However, their study differs from the present study on the count of lower concentration of Bupivacaine (0.025%) used by them as compared to 0.25% Bupivacaine used in the present study. Moreover, the difference in type of surgery can also be held responsible for this variance. In another study, Bellows and Berger[19] did not find a statistically significant difference in pain scores and analgesic dose requirement between preincisional 0.25% Bupivacaine and control group despite having lower mean scores and lesser analgesic dose used. The reason for this could be a smaller sample size (n = 9 in each group) in their study.

The findings of the present study are radically different from the observations made by Victory et al.[20] who observed that neither preincisional nor postincisional Bupivacaine reduced the opioid analgesic requirements or pain scores in study groups as compared to control group. However, the difference between their study and that of ours is the duration of assessment. In the present study, the assessment was limited to 24 h only, however, in their study assessment was made for up to 3 days. We emphasized on early postoperative analgesic need instead of focusing on a prolonged analgesic need measured up to several days as done in their study.

With respect to comparison between two study groups, we found that postincisional group when compared to control group performed slightly better than preincisional group for postoperative cumulative rescue analgesic need but for rest of the assessments (need for first rescue analgesia and frequency of analgesic need) the two groups did not show any significant difference. These findings are similar to that reported by Bourget et al.[21] who used the same drug dose and concentration (40 mL 0.25% Bupivacaine) and found no significant difference between preincisional and postincisional groups with respect to pain control among patients undergoing elective laparotomy. We noticed that preemptive analgesia has a definitive impact in reducing the immediate postoperative pain intensity, prolonging the analgesic effect, and reducing the mean dose and frequency of rescue analgesia. Similar observations were also made by other workers for both pre as well as postincisional groups.[1718] Side effects like nausea and vomiting were minimal and nonsignificant among groups and could be termed as incidental findings dependent on the patient's overall response to different drug interactions and as such could not be attributed to the interventions being done. In none of the studies reviewed by us, such side effects or complications have been reported to be an outcome of pre- and postincisional Bupivacaine infusion.

The findings of this study thus showed that preemptive infusion of Bupivacaine helped to delay the rescue analgesic need for 20–37.5 min and relatively lower intensity of pain during the first 2 h. It also helped to reduce the total amount of rescue analgesic dosage and reducing the frequency of rescue analgesia. Moreover, postincisional Bupivacaine showed to have an edge over the preincisional Bupivacaine. Despite these positive findings, there are limited studies on AH cases and given some conflicting reports in other types of surgeries, further studies are recommended to validate the findings of the present study and also to determine the optimum and most effective dose of local anesthetic.

CONCLUSION

On the basis of findings of the present study, it can be concluded that subcutaneous infiltration of 40 mL of 0.25% Bupivacaine (preincisional or postincisional) helps in reducing the immediate postoperative pain intensity, delays the first rescue analgesic requirement, reduces the postoperative dose, and frequency of rescue analgesia. However, postincisional intervention has an edge over preincisional intervention. The findings of the study are useful from the point of view that no such study has been done in patients undergoing AH. Given the fact that AH is one of the most painful procedures; the findings of the present study have a practical significance. However, in view of paucity of similar studies, further studies to potentiate and validate the findings of the present study are recommended to determine the optimum dose and time of preemptive action.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.