Postoperative analgesia after inguinal hernia repair - Comparison of ropivacaine with bupivacaine: A randomized controlled trial.

BACKGROUND: Postoperative pain management by surgical site infiltration has an edge over other methods of analgesia as it is simple and has lesser side effects. This study was designed to compare the analgesic effects provided by bupivacaine, a classical long-acting local anesthetic and ropivacaine, a new amino amide local anesthetic agent. SUBJECTS AND METHODS: Ninety patients scheduled for elective inguinal herniorrhaphy were randomly allocated to one of the three groups: Group I - R 0.5, group II - R 0.25, and group III - B 0.25. General anesthesia was given. The surgical site was infiltrated before incision with 20 ml of drugs - ropivacaine 0.5% in group I, ropivacaine 0.25% in group II, bupivacaine 0.25% in group III. Intraoperatively hemodynamics were recorded every 15 min until the end of surgery and at the time of skin incision, at the time of cord pulling, and at the time of skin closure. Postoperatively, rest pain, pain on coughing, and pain on movements were assessed using visual analog scale (VAS) score immediately at the end of the surgery and hourly up to 4 h. The time of the first request for rescue analgesia was noted.
RESULTS: VAS scores at rest, during coughing and movements were higher in group R 0.25 and the time of rescue analgesia was shorter with group R 0.25 when compared with other groups.
CONCLUSION: Ropivacaine is less potent than bupivacaine at equal concentrations.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

The goal of postoperative pain management is to reduce or eliminate pain and discomfort with least side effects and minimal cost.[12] Surgical site infiltration has an edge over other methods of analgesia in terms of lesser side-effects and is simple to perform.[3] Infiltration at the surgical site has a limitation that only long-acting local anesthetics provide sufficient duration of analgesia.[4] Bupivacaine is the classical long-acting local anesthetic that has been used successfully for local infiltration. However, large doses of bupivacaine are relatively toxic and even moderate plasma concentrations can cause catastrophic cardiotoxicity.[567]

Ropivacaine is a new amino amide long acting local anesthetic similar in structure to bupivacaine. Ropivacaine is prepared as the S-enantiomer rather than a racemic mixture such as bupivacaine. The previous studies involving the isomers of local anesthetics suggest that the systemic toxicity of the S-enantiomer of various compounds may be lesser than that of racemic preparations.[6] Pharmacologic studies in intact animals indicate that ropivacaine possesses an anesthetic profile similar to that of bupivacaine, but with lower cardiotoxicity.[67] Ropivacaine also produces cutaneous vasoconstriction that restricts the systemic absorption of the drug and increases its local duration of action. Moreover, ropivacaine produces anti-inflammatory activity that may further reduce pain when administered locally.[89] Ropivacaine offers some advantages over bupivacaine, for example, less cardiac and neurological toxicity, less motor blockade, and prolonged sensory analgesia.[10] Both bupivacaine and ropivacaine have been shown to provide analgesia with wound infiltration in the first 3–6 h after hernia repair.[1112] Many patients either refuse neuraxial anesthesia or pose a high risk in view of comorbidities. In this group supplementing general anesthesia with local site infiltration preoperatively will help to reduce the intraoperative requirements, as well as provide the much needed postoperative pain relief. Ropivacaine being a long-acting drug as well as having vasoconstrictor and anti-inflammatory properties may well suit this purpose.

This study was designed to compare the intraoperative requirements and postoperative pain relief with preoperative infiltration of ropivacaine with bupivacaine.

SUBJECTS AND METHODS

This study was registered with Clinical Trial Registration of India (CTRI registration number: CTRI/2014/07/004789). This study was approved by scientific advisory and Institute Ethics Committee (letter number SEC/2011/4/49 dated February 02, 2012). A power analysis based on 95% confidence interval with 80% power and with the mean difference in the visual analog scale (VAS) scores at 5 h of 5 as being significant the sample size of 30 in each group was sufficient.[13] After obtaining written informed consent, 90 patients were enrolled for the study [Figure 1]. The patients belonging to American Society of Anesthesiologists (ASA) physical status I and II and those between the age groups 18 to 70, undergoing elective inguinal hernia repair under general anesthesia, were included in the study. The patients with a known allergy to local anesthetics were excluded from the study.

Figure 1

CONSORT statement for the present study

A standard induction protocol consisting of intravenous (i.v.) propofol 1.5 mg/kg, fentanyl 2 µg/kg, and vecuronium 0.1 mg/kg was used. Anesthesia was maintained with supra glottic airway device with 1–1.2 minimum alveolar concentration isoflurane in the air and O2 mixture. Then the patients were randomized into three groups of 30 each based on opaque sealed envelope technique. Twenty minutes before incision, all patients received 20 ml of study drug. In group R 0.5 – ropivacaine 0.5%, group R 0.25 – ropivacaine 0.25%, and group B 0.25 – bupivacaine 0.25% were used for local site infiltration.

Skin infiltration

Initially, the anterior superior iliac spine was palpated and a mark was made 2 cm medial and 2 cm superior from it. After skin preparation, a 22 gauge needle was blunted and was inserted perpendicular to the skin. Increased resistance was met as the needle encountered the external oblique muscle. A loss of resistance was appreciated once the needle passed through the muscle to lie between external oblique and the internal oblique. After the initial loss of resistance and negative needle aspiration for blood, 5 mL of local anesthetic was injected. The needle was then inserted further to encounter another resistance, which was the internal oblique muscle. A further loss of resistance was appreciated once the needle passed through the internal oblique to lie between internal oblique and the transversus abdominus muscle. After the second loss of resistance, another 5 ml of local anesthetic was administered. Then 5 ml of local anesthetic was given on either side of the site of skin incision.

Parameters studied

Intraoperatively, heart rate and mean arterial pressures were recorded every 15 min until the end of surgery and at the time of skin incision, at the time of cord pulling, and at the time of skin closure. Intraoperative increases in heart rate or mean arterial pressure 20% from the baseline was treated with fentanyl 25 µg and total fentanyl requirement in all the three groups were noted. Patients were reversed after the return of spontaneous respiratory efforts. Postoperatively, rest pain, pain on coughing, and pain on movements were assessed using VAS score immediately after the end of the surgery and then every 1 h up to 6 h. The time of the first request for rescue analgesia was noted and rescue analgesia was provided with injection tramadol 1 mg/kg i.v. on demand or when VAS score more than 5 whichever was earlier. Nausea and vomiting if any was treated with injection ondansetron 0.08 mg/kg. The study ended with the first request of rescue analgesia.

Statistical analysis

The results on continuous measurements were presented on mean ± standard deviation and results on categorical measurements were presented in number (%). SPSS for Windows, Version 16.0. Chicago, SPSS Inc. software was used for analysis. Analysis of variance was used to find the significance of study parameters among three or more groups of patients, the post-hoc Tukey test has been used to find the pairwise significance. Chi-square/Fisher exact test was applied to find the significance of study parameters on a categorical scale between two or more groups. A value <0.05% was considered as statistically significant.

RESULTS

Demographic variables (age and body weight) and ASA status did not differ significantly between groups [Table 1].

Table 1

Patient demographics

Hemodynamics

The base line heart rate as well as during skin incision, cord pulling, and skin closure did not show any significance among the groups [Figure 2].

Figure 2

Comparison of heart rate in the three groups. P > 0.05

The mean blood pressure at base line as well as during skin incision, cord pulling, and skin closure were comparable among the groups [Figure 3].

Figure 3

Comparison of mean arterial pressure in the three groups. P > 0.05

Postoperative analgesia

VAS score was compared among the three groups at rest, during coughing and movement till the first request of analgesic, which was at 4 h (in group R 0.25) in the postoperative period. In the R 0.25 group, the VAS scores were significantly higher at all times when compared with the other two groups [Tables 2–4]. Comparing between groups R 0.5 and B 0.25, the scores were comparable at all times (up to 6 h postoperatively as the first analgesic request was at 6 h in them).

Table 2

Comparison of VAS score at rest in the three groups

Table 4

Comparison of VAS score during movements in the three groups

Rescue analgesic - the demand for rescue analgesic was seen maximum in group R 0.25 within 4–5 h, whereas group R 0.5 and B 0.25 did not ask for rescue analgesic up to 5–6 h [Table 5]. The mean time for rescue analgesic was 247 min in group RO 0.25 where it was comparable in group RO 0.5 and BO 0.25 this is 360 min and 363 min [Table 6].

Table 5

Number of patients who required rescue analgesia in each group

Table 6

Comparison of time of rescue analgesia and opioid requirement in the three groups

Intraoperative opioid requirement was comparable among all the three groups. No adverse events were recorded.

DISCUSSION

An ideal method of providing postoperative pain relief should be easy to administer and should not have adverse effects. In our study, a total of 90 patients scheduled for elective inguinal hernia repair were randomized into three groups - Group R 0.5, group R 0.25, and group B 0.25. None of the patients was excluded from the study after enrolment. All patients received either bupivacaine or ropivacaine as local infiltration. Though various studies have shown wound infiltration with local anesthetics to provide superior analgesia, the results are contradictory.[14] Few studies proved that local infiltration prior to skin incision is better than skin infiltration after the surgery.[14] In our study, ropivacaine was used in concentration of 5 mg/ml (0.5%) and 2.5 mg/ml (0.25%) and bupivacaine in a concentration of 2.5 mg/ml (0.25%). A fixed volume of 20 ml was used for infiltration in all the three groups, whereas in the studies by Erichsen et al. and Pettersson et al. A volume of 40–50 ml was used to provide pain relief after inguinal hernia repair.[1516] The results from our study show that a volume of 20 ml was sufficient to provide effective analgesia, as evidenced from lower VAS scores in the postoperative period. It shows that the large volume is not necessary and can result in higher systemic absorption and potential toxicity. Pettersson et al. had showed that no toxic effects occurred up to 375 mg ropivacaine by estimating serum drug levels (if used for infiltration only).[16] We had used only 100 mg of drug and we did not do serum drug levels as it was well below the established doses. Infiltration technique is also considered to be a factor in postherniorrhaphy pain relief. It is shown that inclusion of subfascial and muscle layers is critical in providing analgesia. In our study, the inclusion of iliohypogastric and ilioinguinal nerves with infiltration of the surgical site was done. Tverskoy et al. have shown that preincisional infiltration and nerve block have a long-term effect and provided better analgesia.[17] In our study also, the infiltration was given before surgical incision, which might explain the lesser need for intraoperative opioids. As these infiltrations were performed in the patient under surgical phase of anesthesia, the adequacy of pain relief intraoperatively could be judged by the hemodynamic parameters and the need for additional analgesics. In our study, the hemodynamic parameters heart rate and mean arterial pressure were comparable in all the three groups' intraoperatively. One patient in group R 0.5 and two patients each in group R 0.25 and in group B 0.25 required additional doses of opioids. In these five patients, surgeons had difficulty in separating the different muscle layers and at the time of pulling the cord.

Our results are supported by Wulf et al. who reported that ropivacaine in a concentration of 0.5%, in addition, to general anesthesia provided adequate postoperative pain relief with the ilioinguinal block.[18] Our results are also consistent with those obtained by Johansson et al. who had shown that 40 ml of 0.25% or 0.5% ropivacaine injected preoperatively provided pain relief for 3 and 6 h, respectively.[14] In our study, ropivacaine 0.5% and bupivacaine 0.25% provided pain relief for 5–6 h after surgery, whereas ropivacaine 0.25% provided pain relief for 3–4 h.

Polley et al. estimated the relative potencies of epidural ropivacaine and bupivacaine and suggested that ropivacaine appears to be 40% less potent than bupivacaine at ED50 concentration but equipotent at a higher concentration.[19] This difference in potency seems to be true as evidenced from our study where ropivacaine in a concentration of 0.5% seemed to be equipotent to bupivacaine 0.25%. The time for rescue analgesia is shorter with ropivacaine 0.25% group. The VAS scores at rest, coughing, movements were similar between the groups; ropivacaine 0.5% and bupivacaine 0.25%. The VAS scores in group ropivacaine 0.25% were higher from the immediate postoperative period when compared with the other two groups.

Limitations of our study were, we did not assess the time to void in these patients, so the advantage of this infiltration technique over the feasibility of subarachnoid block for ambulatory surgery could not be commented upon. We did not measure the plasma concentration of the local anesthetic agents, as reported in other studies.

CONCLUSION

Ropivacaine is less potent than bupivacaine at equal concentrations. About 0.5% ropivacaine provides excellent postoperative analgesia, which is comparable to the conventional use of 0.25% of bupivacaine. Ropivacaine though is said to have vasoconstrictive effects, prolonging the duration of action is less potent than bupivacaine at equal concentrations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest

Table 3

Comparison of VAS score during coughing in the three groups