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 Table of Contents  
Year : 2019  |  Volume : 8  |  Issue : 13  |  Page : 18-23

Postincision wound infiltration with bupivacaine versus pethidine for postoperative pain relief following myomectomy under spinal anesthesia

Department of Anaesthesiology, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria

Date of Web Publication19-Feb-2019

Correspondence Address:
Idehen Osazuwa Hanson
University of Benin Teaching Hospital, Benin City, Edo State
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/nnjcr.nnjcr_27_18

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Context: Bupivacaine is commonly used agent for wound infiltration because of its local anesthetic effect. However, pethidine an opioid has both local anesthetic and systemic analgesic effect. The combined analgesic effect of pethidine may be superior to bupivacaine that has only a local anesthetic effect. Few studies have however supported the superiority of pethidine over bupivacaine for wound infiltration. Aims: The aim of this study is to evaluate the analgesic effect of pethidine in comparison with bupivacaine wound infiltration for postoperative pain control in nonparturients scheduled for myomectomy under spinal anesthesia. Setting and Design: This study is a prospective, randomized, double-blinded control trial of the analgesic efficacy of plain bupivacaine versus pethidine for patients scheduled for myomectomy under spinal anesthesia in a Tertiary Healthcare center in Nigeria. Subjects and Methods: Seventy-six American Society of Anesthesiologists 1 and 11 patients billed for myomectomy using spinal anesthesia were randomized into two groups. Group bupivacaine had wound infiltration with 50 mg isobaric bupivacaine at a concentration of 0.25%. Group pethidine had 1 mg/kg pethidine. In the ward, pain was assessed at various intervals at rest and on coughing using the numerical rating scale (NRS) pain assessment tool and the time of the first analgesic request. Statistical Analysis: NRS scores were presented as median with interquartile range, Continuous variables such as duration of analgesia and total analgesic consumption were analyzed using the unpaired Student's t-test. Results: The pethidine group had a longer time to first analgesic request, lower pain scores and a higher level of satisfaction. Conclusion: This study showed that postincision wound infiltration with pethidine at 1 mg/kg as a component in multimodal analgesia is more effective than 0.25% bupivacaine in the management of postmyomectomy pain.

Keywords: Bupivacaine, local anesthetic, opioid pethidine, wound infiltration

How to cite this article:
Jaja UC, Amadasun FE, Hanson IO. Postincision wound infiltration with bupivacaine versus pethidine for postoperative pain relief following myomectomy under spinal anesthesia. N Niger J Clin Res 2019;8:18-23

How to cite this URL:
Jaja UC, Amadasun FE, Hanson IO. Postincision wound infiltration with bupivacaine versus pethidine for postoperative pain relief following myomectomy under spinal anesthesia. N Niger J Clin Res [serial online] 2019 [cited 2019 Jul 15];8:18-23. Available from: http://www.mdcan-uath.org/text.asp?2019/8/13/18/252584

  Introduction Top

Pain complicates perioperative care following surgery. The consequences of this could vary from immobility to a prolonged recovery period. Adequate postoperative pain relief is therefore, vital in preventing problems, such as cardiac complications (tachycardia, hypertension), pulmonary complications (atelectasis), prolonged hospital stay, insomnia, delayed wound healing, deep vein thrombosis, development of neuropathic pain, and high cost of care, which may all be associated with pain.

The overall approach to pain management has shifted from an opioid-based mono-therapy to a multimodal approach.[1] Wound infiltration is a component of multimodal pain management. The commonly used agents are local anesthetics like bupivacaine and rarely pethidine which has being shown to have both local anesthetic effect[2] and systemic analgesic effects. Pethidine may, therefore, be superior to bupivacaine that has only a local anesthetic effect.

A recent study has shown surprisingly, that pethidine is a better drug compared to bupivacaine following wound infiltration for pain relief in parturients after cesarean delivery.[3] However, could it be that the anatomical changes such as variation in abdominal wall tension and physiological changes that occur during pregnancy contributed to the outcome observed? Would the observation or result be different in procedures on non parturients? There is also a paucity of studies that compare the relative efficacy of bupivacaine and pethidine wound infiltration in nonparturients for postoperative pain relief.

The aim of this study was to evaluate the comparative efficacy of bupivacaine and pethidine wound infiltration for postoperative pain relief, following myomectomy under spinal anesthesia.

  Subjects and Methods Top

This was a prospective, randomized, double-blind clinical study. The study was carried in a tertiary healthcare center in Nigeria. The study population was drawn from female patients aged 21–45 years of the American Society of Anesthesiologists (ASA) Physical Health Status I and II, who were scheduled for myomectomy under spinal anesthesia. A sample size of 76 patients was needed to achieve a 29% improvement in the postoperative analgesic duration in a previous study[4] using α = 0.05, β = 0.2 derived from a formula.[5]

Exclusion criteria were patient's refusal, conversion to general anesthesia, patients with diabetes, obesity (body mass index [BMI] >30 kg/m2), peptic ulcer disease, asthma, seizure disorder, bleeding disorder, and known allergy to local anesthetics, opioids, or nonsteroidal anti-inflammatory drugs. Others are patients with chronic hepatic illness, renal illness, and contraindications to spinal anesthesia, neurological or psychiatric disorders, significant alcohol abuse and those who had myomectomy via a longitudinal incision or repeat myomectomy.

Informed consent and randomization

Ethical clearance was obtained from the Research and Ethics Committee of the Hospital. Written consent was obtained from those who met the inclusion criteria during preoperative evaluation. All the patients were trained in the use of the numerical rating scale (NRS) pain assessment method. Randomization was done using computer-generated allocation. The study drugs were prepared by an anesthetist while the surgeon did the wound infiltration. Group 1 (bupivacaine) patients received wound infiltration with 50 mg isobaric bupivacaine at a concentration of 0.25%, constituted to a total volume of 20 ml with sterile water. Group 2 (pethidine) patients had 1 mg/kg pethidine diluted into a total volume of 20 ml with sterile water.

Study protocol

Routine preoperative evaluation done, investigations were ordered, and blood was grouped and cross-matched against donor's blood. All patients were fasted and premedicated with tablet diazepam 5 mg at night and morning of surgery to allay anxiety.

Vital signs were taken using a DASH 400 multi-parameter monitor (manufactured by GE Medical System Information Technology International, Wisconsin USA). Intravenous access was established with a 16G cannula and secured; each patient's circulation was preloaded with Ringer's lactate using 15 ml/kg.

Spinal anesthesia was induced under aseptic conditions at L3/L4 intervertebral space, with the patient in the traditional sitting position. Each patient in both groups received 3 ml of hyperbaric 0.5% bupivacaine (B Marcaine®, Astra-zeneca, Sweden) via a 26G pencil point Whitacre spinal needle. The level of sensory block was assessed; the maximum block height of T6-T5 was regarded as adequate for surgery to commence.

Monitoring of vital signs, urine output, and blood loss continued throughout the period of anesthesia and surgery.

Fluid maintenance was achieved with warm Ringer's lactate, and blood transfused when the trigger point was exceeded. Hypotension (>25% drop from baseline blood pressure or mean arterial blood pressure ≤60 mmHg) was treated with intravenous fluid infusion and/or 3 mg aliquots of ephedrine. Breakthrough pain was treated with intravenous injection of 30 mg pentazocine, and patients with breakthrough pain requiring treatment with pentazocine (30 mg) were excluded from the study.

The study medications were drawn into two identical 20 ml syringes (precoded). This was done in the absence of the investigator and the patient. At the end of the surgery, pain was assessed using the NRS and the patients in Group 1 received wound infiltration by the surgeon with 50 mg isobaric bupivacaine at a concentration of 0.25%, total volume 20 ml. The infiltration was done along incision site with hypodermic needle (22G; 50 mm) being inserted every 3 cm at a 45° angle to the skin. After needle insertion, following a negative blood aspiration test, infiltration was made in a fan-like manner while the needle was being withdrawn. Group 2 patients had their wound infiltrated in a similar manner with 1 mg/kg pethidine total volume of 20 ml.

Both groups received 50 mg rectal diclofenac after obtaining informed consent from patients, co-administered with intravenous infusion paracetamol (perfaglan®) 1 g at the end of the surgery. This initial dose of both paracetamol and rectal diclofenac were not included in the total analgesic consumption in 24 h postoperatively. This is so because both drugs were administered intraoperatively and not in the postoperative period.

Thereafter, patients were then transferred to the postanesthetic care unit (PACU). In the ward, pain was assessed at rest and on coughing every 30 min after arrival from PACU, then hourly until 6 h thereafter at the 12th h and 24th h after surgery. The time of the first analgesic request from the time of administration of study drugs was recorded as well as the pain scores at the time of the first analgesic request. Thereafter, postoperative analgesia was maintained by the nurses using the routine obstetrics and gynecology protocol of intramuscular pentazocine, 30 mg 6 hourly with rectal diclofenac 50 mg 8 hourly. The total analgesic consumption in the first 24 h postoperatively was also recorded.

The incidence of side effects related to study drugs such as nausea and vomiting/retching were to be graded using an ordinal scoring system of 0 = no symptoms, 1 = mild symptom not requiring treatment, 2 = moderate symptom requiring treatment, and 3 = symptom persisting despite treatment.

Data analysis

Data entry and analysis were performed using SPSS®(Statistical package for the social sciences) version 16. Parametric data were presented as means with standard deviation and categorical data presented as counts or frequencies. NRS scores were presented as median with interquartile range. Continuous variables such as age, weight, height, BMI, pulse rate blood pressure, duration of analgesia, and total analgesic consumption were analyzed using the unpaired Student's t-test. Associations between categorical variables (ASA, level of satisfaction), were analyzed using Chi-square test or the Fisher's exact test where applicable. The Mann–Whitney U-test was used to compare median NRS score. The significance level was determined as a value of P < 0.05. All tests were two-tailed.

  Results Top

Seventy-six ASA 1 or 2 gynecological patients aged between 21 and 45 years were recruited for this study, with 38 patients, in each Group. There were 23 ASA 1 (60.5%) and 15 ASA 2 (39.5%) patients in Group 1. Group 2, had 25 ASA 1 (66.7%) patients and 13 ASA 2 (33.3%) patients [Table 1].
Table 1: Patient demographic characteristics, duration of surgery, and American Society of Anesthesiologists status

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Meantime from study drug administration to first analgesic request after surgery, for both groups is as shown [Table 2]. The median NRS pain scores at rest between Groups 1 and 2 are as represented in [Table 3]. The median NRS pain scores at rest were similar between the two groups 1 h postoperatively (1 [0–3] vs. 1 [0–2]), for Groups 1 and 2, respectively (P = 0.883). Similarly, comparable pain scores were observed in the 2nd h postoperatively (2 [1–4 vs. 1 [0–3]), P = 0.374.
Table 2: Time to first analgesic request and pain scores in Groups 1 and 2

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Table 3: Postoperative numerical rating scale scores at rest in Groups 1 and 2

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From the 3rd h up to the 6th h, there were statistically significant differences in the median NRS pain scores between both groups. Group 1 had higher median pain scores compared to Group 2. Further analysis of the results revealed that by the 2nd h, six patients had received additional analgesia in Group 1; at this time, no patient in Group 2 had received analgesia. By the 3rd h nineteen patients in Group 1 had received additional analgesia, whereas none had analgesia in the Group 2. At the 5th and 6th h, 30 and 36 patients, respectively, in Group 1, had received additional analgesia compared to 10 and 29 patients recorded to have received analgesia in Group 2 within the same time frame. Median pain score at 6th h was 6 (4–7) in Group 1 at rest as against 3 (2–6) in Group 2 with a P < 0.001.

The pain scores on coughing were comparable in the two Groups in the 1st h and 2nd h postoperatively, P = 0.702 and 0.274, respectively. Group 1 had higher median pain scores on the average compared to Group 2 on coughing. Median pain scores between both groups were statistically significant from the 3rd h up to the 6th h as shown in [Table 4].
Table 4: Postoperative numerical rating scale scores on coughing in Groups 1 and 2

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The mean total analgesic consumption in milligrams for 24 h, pentazocine was also not statistically significant this is shown in [Table 5].
Table 5: Mean total analgesic consumption in the 24 h postoperative period in Groups 1 and 2

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There was a significant difference in patient's satisfaction with pain relief between Group 1 and Group 2 P = 0.017. More patients in Group 1, (6 [7.6%]) were not satisfied with their pain control compared to (1 [1.30%]) in Group 2 patients; this is shown in [Table 6]. Mild pruritus was observed in 6 (15.78%) patients of Group 2, none in Group 1. No other side effects related to the study medications were observed in both groups.
Table 6: Patient satisfaction with pain relief in Groups 1 and 2

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  Discussion Top

This study showed that wound infiltration with 1 mg/kg pethidine provided more effective postoperative analgesia when compared with wound infiltration with 0.25% bupivacaine following myomectomy under subarachnoid block. Patients who had pethidine had lower pain scores; longer time to first analgesic request and higher level of satisfaction compared with those who had bupivacaine. However, there was no demonstrable statistically significant difference in the total analgesic consumption within the first 24 h postoperatively in both groups.

The superior analgesic effect of pethidine infiltration may be connected with the speculated local analgesic properties of pethidine.[6] The effects of pethidine appear to be produced by its actions on two independent pathways; the opioids receptor pathways, which subserve analgesic action, and the sodium channels, which lead to local anesthetic action. The combined systemic analgesic and local anesthetic effects may account for the superior analgesia when compared with bupivacaine that has only local anesthetic effect as observed in this study. Jabalameli et al. evaluated the effects of infiltration with pethidine.[3] Their results showed that pethidine alone had superior analgesic effect over bupivacaine, as evidenced by a reduction in analgesic consumption.

Pethidine, like fentanyl, is one of the opioids that is highly lipophilic. Indeed, Chander et al.[7] found that fentanyl had a better analgesic profile when compared to bupivacaine for wound infiltration. The findings of increased duration of analgesia and reduced postoperative analgesic consumption as demonstrated by these authors may be due to the lipophilic properties of fentanyl, just like pethidine. It is thought that this peripheral opiate anti-nociception is mediated through λ as well as κ receptors located on primary afferent veins; pethidine has affinity for these receptors as well.

Pain control was consistently better in the patients who received pethidine as evidenced by lower NRS pain scores at all timelines except in the 1st and 2nd h. The similarity in the pain scores observed within the 1st and 2nd h could be attributable to the fact that patients still had some degree of residual analgesia from spinal anesthesia. Second, this period corresponds to the time of peak action of the drugs co-administered (paracetamol and diclofenac) at the end of surgery as components of the multimodal analgesic regimen.

Up to the 3rd h, all patients who received pethidine were pain-free compared with half of the patients in the bupivacaine group who had received analgesia both at rest and on coughing. This has clinical implication, in that pethidine wound infiltration provided 100% pain-free periods till the 3rd h unlike those who received bupivacaine that never had such analgesic coverage. Could bupivacaine wound infiltration have had better analgesic effect if the concentration used was higher than 0.25%? The effect of local anesthetics (anesthesia and analgesia) is dose-dependent, higher concentration may eventually translate to a higher dose in a milligram. Al-Hakim and Alidreesi[8] evaluated the effects of local anesthetic infiltration, on postoperative pain after cesarean section under spinal anesthesia. They reported lower pain scores with the use of 0.5% bupivacaine following wound infiltration.

On the other hand, significant differences in pain scores between the pethidine and bupivacaine group were observed from the 3rd to the 6th h postoperatively. Similar finding was also observed by Jabalameli et al. that reported lower pain scores (visual analogue scale) with the use of pethidine wound infiltration, compared to bupivacaine within 24 h period postoperatively.[3]

Other authors refuted the superiority of pethidine. Forgach and Ong investigated the effect of pethidine wound infiltration on postoperative pain relief following laparoscopic tubal ligation under general anesthesia.[9] Failure to observe any effect on postoperative pain control as reported by these authors might be due to the type of surgery (laparoscopic tubal ligation). Furthermore, postoperative pain management of intra-abdominal surgeries is poorly managed with local anesthetic wound infiltration, also the entry point for laparoscopic surgery is often minimal. This is typical of laparoscopic surgeries with little or no pain at the entry point when compared to pain emanating from open intra-abdominal surgeries which are better managed with systemic analgesics.

The NRS pain scores on coughing (movement) were higher than that at rest in both groups in our study; this is not unexpected because dynamic pain scores are generally higher than pain at rest. Coughing was employed in assessing pain intensity on movement, although a more accurate choice would have been deep knees bend. However, this was not the case because pain assessment started immediately after surgery and as at that time participants still had some degree of the residual motor block from spinal anesthesia. As a result of this, lower limb movement was almost impossible, hence coughing was used. In addition, coughing underscores the quality of pain control. Poor pain control may result in impaired coughing leading to atelectasis of the alveoli, stasis, bacterial invasion, and consequent lung infection.

Participants who had pethidine reported lower overall pain scores compared to patients who received bupivacaine in the postoperative period. Furthermore, median NRS pain scores at the time of first analgesic request showed that patients in both groups requested additional analgesia at moderate pain scores that is between NRS score of 4–6. In all, pethidine wound infiltration had lower pain scores compared to bupivacaine. This implies a better analgesic profile. Soyannwo[10] and Cakan et al.[11] also reported remarkable differences in pain scores between study groups, with lower pain scores being observed in groups that had improved quality of analgesia.

Another method of assessing the quality of analgesia is with the use of time to first analgesic request. Shorter time to first analgesic request is indicative of poor analgesic quality.

However, on the contrary, a longer time to first analgesic request implies better analgesia. In this study, patients who received wound infiltration with pethidine had prolonged duration of effective analgesia as shown by a longer time to first analgesic request (320 min) compared to the bupivacaine wound infiltration (150 min). This is surprising, as local anesthetics such as lidocaine and bupivacaine are conventionally known as the gold standard for wound infiltration analgesia. Could this change the long-held tradition because of this superiority of pethidine wound infiltration? This seeming superior analgesic effect of pethidine infiltration over bupivacaine adds value to our observation.

Satisfaction scores for pain relief among patients were higher in the participants who had pethidine, compared to bupivacaine infiltration analgesia. Jabalameli et al. similarly reported higher patient satisfaction with analgesia when pethidine wound infiltration was applied for postoperative cesarean section pain control.[3] It has also been established that the patient's satisfaction is closely tied to the effectiveness of pain management.[12]

Additional factors besides effective pain management which could influence satisfaction are the overall patient's care, socioeconomic status, and expectations.[13] The socioeconomic status of individual patients has some influence on satisfaction, in that patients from low social class are more likely to be satisfied compared to those in the high social class.[13] Closely related also to this, is the involvement of patient expectations. High levels of overall patients satisfaction are linked to meeting preoperative expectations of surgery, achieving satisfactory pain relief following surgery and the overall hospital experience.[14]

There were no side effects such as nausea or vomiting, except mild pruritus attributable to study medication. The absence of these side effects aforementioned might be due to the fact that paracetamol infusion was co-administered in this study, as a component of multimodal analgesic regimen. Some authors have demonstrated that paracetamol infusion possesses antiemetic effect.[12] Cakan et al. also observed antiemetic effect when intravenous paracetamol was infused after lumber laminectomy and discectomy.[11]

Another possible reason for the absence of side effects was the route of administration of study drugs. It is a known fact that opioids, when given intravenously and sometimes orally, could provoke nausea and vomiting. However, with wound infiltration (subcutaneous) using opioids (pethidine) this may not be the case because systemic absorption might be slow and erratic. Consequently, could it be possible that the needed plasma concentration of the drug that would provoke nausea or vomiting was not achieved?

Overall, no patient had pruritus amongst the bupivacaine group in this study. Pruritus usually is not a known side effect of bupivacaine wound infiltration. However, amino ester local anesthetics are known to cause pruritus due to their tendency to produce allergic reactions.

On the other hand, opioids in some patients may give rise to pruritus which is speculated to be related to histamine release. Conversely, this (histamine release) is higher with the naturally occurring alkaloids such as morphine and not the synthetic opioids like pethidine.

Mild itching was observed in 6 participants in the pethidine group in this study.

However, this did not warrant any treatment, because it resolved completely very shortly (1–2 min) after the onset.

  Conclusion Top

This study showed that postincision wound infiltration with pethidine at 1 mg/kg is more effective than 0.25% bupivacaine in the management of postmyomectomy pain. The inclusion of wound infiltration with pethidine as a component in multimodal analgesia is effective in the management of postmyomectomy pain.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Angle P, Walsh V. Pain relief after caesarean section. Tech Reg Anesth Pain Manag 2001;5:36-40.  Back to cited text no. 1
Wagner LE 2nd, Eaton M, Sabnis SS, Gingrich KJ. Meperidine and lidocaine block of recombinant voltage-dependent Na+channels: Evidence that meperidine is a local anesthetic. Anesthesiology 1999;91:1481-90.  Back to cited text no. 2
Jabalameli M, Safavi M, Honarmand A, Saryazdi H, Moradi D, Kashefi P, et al. The comparison of intra-incisional injection tramadol, pethidine and bupivacaine on post-caesarean section pain relief under spinal anesthesia. Adv Biomed Res 2012;1:53.  Back to cited text no. 3
Ige O, Kolawole I, Bolaji B. Opioid-sparing effect of bupivacaine wound infiltration after lower abdominal operations. J West Afr Coll Surg 2011;1:62-82.  Back to cited text no. 4
Whitley E, Ball J. Statistics review 4: Sample size calculations. Crit Care 2002;6:335-41.  Back to cited text no. 5
Jaffe RA, Rowe MA. A comparison of the local anesthetic effects of meperidine, fentanyl, and sufentanil on dorsal root axons. Anesth Analg 1996;83:776-81.  Back to cited text no. 6
Chander R, Liddle D, Kaur B, Varghese M. Wound infiltration with plain bupivacaine as compared with bupivacaine fentanyl mixture for postoperative pain relief after abdominal surgery. Anesth Essays Res 2011;5:142-6.  Back to cited text no. 7
  [Full text]  
Al-Hakim NH, Alidreesi ZM. The effect of local anaesthetic wound infiltration on post operative pain after caesarean section. J Surg Pak 2010;15:131-4.  Back to cited text no. 8
Forgach L, Ong BY. Failure of meperidine wound infiltration to reduce pain after laparoscopic tubal ligation. Can J Anaesth 1995;42:1085-9.  Back to cited text no. 9
Soyannwo OA. Post-operative pain control – Prescription pattern and patients' experience. West Afr J Med 1999;18:207-10.  Back to cited text no. 10
Cakan T, Inan N, Culhaoglu S, Bakkal K, Başar H. Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements. J Neurosurg Anesthesiol 2008;20:169-73.  Back to cited text no. 11
Moon YE, Lee YK, Lee J, Moon DE. The effects of preoperative intravenous acetaminophen in patients undergoing abdominal hysterectomy. Arch Gynecol Obstet 2011;284:1455-60.  Back to cited text no. 12
Naseer M, Zahidie A, Shaikh BT. Determinants of patient's satisfaction with healthcare system in Pakistan: A critical review. Pak J Public Health 2012;2:52.  Back to cited text no. 13
Hamilton DF, Lane JV, Gaston P, Patton JT, Macdonald D, Simpson AH, et al. What determines patient satisfaction with surgery? A prospective cohort study of 4709 patients following total joint replacement. BMJ Open 2013;3. pii: e002525.  Back to cited text no. 14


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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