|Year : 2018 | Volume
| Issue : 2 | Page : 66-72
A comparative study of ropivacaine and bupivacaine with fentanyl for postoperative patient-controlled epidural analgesia after major abdominal oncosurgery
Anita Kulkarni, Anudita Gupta, Shagun B Shah, Ajay K Bhargava
Department of Anaesthesiology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, Delhi, India
|Date of Web Publication||31-Dec-2018|
Shagun B Shah
House No. 174–175, Ground Floor, Pocket 17, Sector 24, Rohini, Delhi 110085
Source of Support: None, Conflict of Interest: None
Aim: To compare the analgesic efficacy of epidural ropivacaine–fentanyl with bupivacaine–fentanyl combination administered by patient-controlled epidural analgesia (PCEA) technique for postoperative pain relief after major abdominal oncosurgery. Materials and Methods: A prospective, randomized, interventional, parallel group, active control study was conducted on 60 patients with American Society of Anesthesiologists physical status I–III. Random allocation was carried out into two groups of 30 patients each. Intraoperatively, after administering a loading dose (10mL of 0.5% bupivacaine) in both the groups, continuous infusions of 0.1% bupivacaine plus fentanyl (2 µg/mL) (Group BF) or 0.1% ropivacaine plus fentanyl (2 µg/mL) (Group RF) were started at the rate of 5mL/h. Postoperatively, same drug concentrations were administered via PCEA pump at 4mL/h as a baseline infusion (bolus dose, 3mL; lockout interval, 15min). Visual analog scale (VAS) score at rest and on coughing was recorded at specific time points. Rescue analgesia was administered as per protocol. Results: VAS scores at rest and on coughing were higher in Group BF as compared to Group RF. Group RF had less drug consumption, required fewer PCEA boluses, and had minimal motor blockade as compared to Group BF. Conclusion: Good analgesic efficacy with lower drug consumption makes Group RF well suited for postoperative PCEA with hemodynamic stability and minimal motor blockade.
Keywords: Bupivacaine, fentanyl, patient-controlled epidural analgesia, ropivacaine
|How to cite this article:|
Kulkarni A, Gupta A, Shah SB, Bhargava AK. A comparative study of ropivacaine and bupivacaine with fentanyl for postoperative patient-controlled epidural analgesia after major abdominal oncosurgery. J Curr Oncol 2018;1:66-72
| Introduction|| |
Effective acute postoperative pain relief (POPR) after major abdominal surgery leads to cardiovascular stability, patient satisfaction, early mobilization, early enteral feeds, and reduced hospital stay. Both epidural ropivacaine and bupivacaine can be used for this purpose, individually or in combination with opioids.,
Patient-controlled epidural analgesia (PCEA) has several advantages over intravenous (IV) patient controlled analgesia (PCA), including superior analgesia, suppression of stress response to surgery, and safety.,,
Our null hypothesis was that ropivacaine with fentanyl has less analgesic potency than bupivacaine with fentanyl when administered via PCEA for POPR. Our primary objective was to compare same concentration of epidural ropivacaine with fentanyl and bupivacaine with fentanyl administered by PCEA technique after major abdominal oncosurgery. Our secondary objectives were to evaluate motor and sensory blockade and to study the incidence of any hemodynamic, neurological, and other side effects.
| Materials and Methods|| |
This prospective, randomized, interventional, single-centric clinical study was conducted from March 25, 2015, to February 20, 2016, after approval from the institutional review board and scientific committee and after obtaining written informed consent from all patients. The study population included 60 women who were normotensive, aged 45–65 years, American Society of Anesthesiologists (ASA) physical status I–III, weighing 45–75kg, and posted for elective major abdominal oncosurgery via a vertical midline infraumbilical incision.
The exclusion criteria were patient refusal for regional anesthesia; contraindication to regional anesthesia (coagulopathy or localized infection); history of allergic reaction to bupivacaine, ropivacaine, or fentanyl; history of opioid or substance abuse; major spine deformity/surgery; or neurological deficit of lower limbs.
This single-blind study comprised a sample size of 60 patients randomly allocated into two groups Group RF (0.1% ropivacaine plus fentanyl, 2 µg/mL) and Group BF (0.1% bupivacaine plus fentanyl, 2 µg/mL). After normal distribution had been ascertained by the Kolmogorov–Smirnov test, a sample size of 30 patients in each group was arrived at according to the standard normal distribution theory and fixing type I error (α) at 0.05 and the power of the study (1 – β) at 0.8. According to simple random sampling technique, of all the cases that fulfilled the inclusion criteria, every odd-numbered case was assigned to Group RF and every even-numbered case to Group BF.
Intraoperatively, after administering a loading dose (10mL of 0.5% bupivacaine) in both the groups, continuous infusions of 0.1% bupivacaine plus fentanyl (2 µg/mL) (Group BF) or 0.1% ropivacaine plus fentanyl (2 µg/mL) (Group RF) were started at the rate of 5mL/h according to the study group. Later, postoperatively, same concentration of study drug was set on a PCEA pump at the rate of 4mL/h as a continuous baseline infusion with a PCEA bolus dose of 3mL and lockout interval of 15min.
Visual analog scale (VAS) score at rest and on coughing was recorded at 0h (10min post-extubation), 1, 6, 12, 18, and 24h using 0–100mm VAS score. According to our institutional protocol, the patients with major abdominal surgery are ambulated only after 24h. Hence, we could not study the effect of both the groups on patient mobility. Patients were not given any other analgesics such as nonsteroidal anti-inflammatory drugs. Rescue analgesia, IV morphine (3mg), was given if the patients in either group had VAS >3 at rest and VAS >5 on coughing despite activating the PCEA demand button. PCEA data such as the number of good attempts and total dose (continuous infusion plus bolus dose) were noted from the PCA pump display. The extent of upper and lower sensory blockade for loss or return of sensation was determined by pinprick method with a blunt 27-gauge needle. Hemodynamic data such as heart rate (HR) and mean arterial pressure (MAP) levels were monitored. Motor blockade was assessed according to a four-point Bromage score. If Bromage score was higher than 2, then PCEA pump was stopped till Bromage score became 2, and the infusion was restarted. Sedation score, respiratory rate and oxygen saturation, and adverse events such as nausea and vomiting, hypotension, shivering, and pruritus were noted.
Taking reference from the study by Pouzeratte et al., we performed a power analysis using postoperative pain at rest as the primary outcome variable. We calculated a sample size so that an intergroup mean difference in VAS of 2cm would allow a type I error of α at 0.05 and the null hypothesis would be retained with type II error of β at 0.2. A sample size of 19 patients per group was found necessary after this analysis. We selected a sample size of 30 patients to increase the power and allowing for dropouts.
Statistical analysis: All postoperative variables were compared with multivariate repeated measurement analysis using unpaired t-test. Chi-square test was performed for categorical variables such as nausea/vomiting and rescue IV morphine requirement. IBM SPSS (International Business Machines; Statistical Package for the Social Sciences) statistics for windows (version 19.0; Armonk, NY: IBM Corp.) was used and P < 0.05 was considered statistically significant. Results were expressed as mean ± standard deviation (SD) in tabular form and bar and line diagrams.
| Results|| |
Demographic data as well as other data such as ASA grade, type and duration of surgery, intraoperative fentanyl requirement, and epidural catheter level in two groups were comparable (P > 0.05) [Table 1].
The flow of patients is depicted in the consolidated standards of reporting trials (CONSORT) diagram [Figure 1].
|Figure 1: CONSORT diagram showing the flow of participants through each stage of the randomized trial|
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The mean pain scores measured using 0–10cm VAS ranged between 1.8 and 4.6cm during the entire study period [Table 2]. Although patients in both the groups reported pain scores at rest of less than 3.5cm throughout, a significant proportion scored over 3.5cm on coughing during 0–18h postoperative period. Especially, VAS scores at rest and on coughing were more in Group BF as compared to Group RF as seen in [Table 2] (P < 0.05). This shows that Group RF patients had better pain relief at rest throughout the study period and on coughing after 12h of study drug consumption as compared to Group BF. Twenty-two patients in Group BF and 12 patients in Group RF required rescue analgesic morphine in a bolus dose of 3mg.
|Table 2: Mean VAS scores at rest and on coughing at different time intervals|
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Pressing the PCEA demand button within the lockout time of 15min of receiving the bolus drug does not administer bolus drug to the patient as a safety feature. The patients belonging to Group BF required more additional PCEA boluses for achieving good pain relief than those belonging to Group RF at 12, 18, and 24h, and this difference was statistically significant at 12h (P < 0.05) and highly significant (P < 0.001) at 18 and 24h of study. The mean total number of attempts was also more in Group BF as compared to Group RF. The results are statistically significant (P < 0.001) at 12, 18, and 24h. Total amount (continuous infusion plus received PCEA bolus on demand) of study drug consumed at 1 and 6h was similar in both the groups. Mean total drug consumption at 12 (P < 0.05), 18 (P < 0.010), and 24h (P < 0.001) was significantly less in Group RF as compared to Group BF [Table 3].
|Table 3: Mean total drug consumption, mean PCEA bolus good attempts, and mean total PCEA attempts|
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Motor block of low intensity was observed in both the groups, as the patients were able to flex their knees and freely move their ankles (Bromage score <2). No statistically significant difference in motor block was observed, assessed by the Bromage score, at any point of time [Table 4].
|Table 4: Mean Bromage scores and mean sedation scores in both the groups at various time points postoperatively|
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The regression phase was shorter (up to 6h) with Group RF than with Group BF, followed by no residual motor block in both the groups till 24h.
None of the patients exceeded Sedation score 2 [Table 4]. The patients in Group BF were found to be slightly more sedated immediately after operation up to 6h as compared to Group RF, but this difference was statistically not significant (P > 0.05).
The HR and MAP levels at different time intervals (0, 1, 6, 12, 18, and 24h) in the postoperative period are shown in [Figure 2]. No significant increase (>120 beats per min) or decrease (<50 beats per min) was observed in HR as compared to baseline values at different time intervals in both the groups. However, MAP values decreased significantly in Group BF as compared to Group RF at 6h, and the difference was statistically significant (P value <0.05).
|Figure 2: Hemodynamic changes in bupivacaine–fentanyl (BF) and ropivacaine–fentanyl (RF) groups|
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Significant hypotension was reported in five patients of which four belonged to Group BF. In these patients, PCEA was temporarily halted and then restarted with a decreased background infusion. The most frequent adverse event, nausea and/or vomiting, occurred in 10 patients in BF and 8 patients in Group RF, respectively. Three patients in Group RF complained of shivering. One patient in each group complained of mild backache postoperatively. None of the patients had respiratory depression, fall in oxygen saturation, or pruritus.
| Discussion|| |
Ropivacaine is a relatively new amino-amide local anaesthetic (LA), structurally similar to bupivacaine. Propyl group replaces butyl group on the piperidine nitrogen atom in ropivacaine. Ropivacaine blocks Aδ and C fibers to a greater degree than the Aβ fibers that control motor function. Studies have confirmed that equal volumes and concentrations of ropivacaine and bupivacaine produce a similar pattern of sensory block, but motor block is slower in onset, less intense, and of shorter duration with ropivacaine.,,,,
PCEA decreases drug requirements when compared with continuous epidural infusion in surgical populations. PCEA reduces motor block owing to reduced local anesthetic consumption, which is consistent with our study. PCEA with background infusion and boluses decreases the requirement for epidural top-ups and consumption of systemic rescue analgesia, with a consequent reduced intervention by acute pain physicians because patients can self-titrate analgesia. PCEA provides a patient-free access to analgesia to obtain satisfactory pain control; hence, it is not surprising that pain relief at rest in both the groups was equally satisfactory.
Compared with the equiconcentration of bupivacaine, ropivacaine produces equivalent analgesia with less motor blockade,and reduced cardiac and central nervous system toxicity. In this study, we measured VAS pain scores with patient at rest akin to many postoperative epidural opioid studies. Postoperative VAS scores at rest were between 2 and 4 in Group BF patients compared with Group RF patients who had VAS scores <3 at rest, but this difference was statistically not significant (P > 0.05). Mean VAS score on coughing at 12, 18, and 24h after surgery in Group RF was lower (<4) as compared to Group BF (>4), and this difference was statistically significant (P < 0.05), thus proving the efficacy of ropivacaine in providing effective postoperative analgesia and promoting good chest physiotherapy and decreasing postoperative respiratory complications.
For effective postoperative epidural analgesia, adding opioid to LA causes synergistic action in substantia gelatinosa at the dorsal horn of the spinal cord, enhances duration and intensity of analgesia, and also reduces LA dose and related side effects such as sympathetic and motor blockade. Fentanyl (1–5 µg/mL) is the opioid often used in combination with LA, and its mechanism of postoperative analgesia is primarily systemic. However, some studies suggest that a spinal effect may occur after epidural administration of fentanyl.
The rescue analgesic requirement during the study in both the groups was highly significant. Mean morphine consumption in Group BF was more as compared to Group RF (P value <0.05). In Group RF, only 40% of patients required rescue analgesic throughout the study period, whereas in Group BF, 73% of patients required morphine.
Studies have confirmed that equal volumes (rate of infusion) and concentrations of ropivacaine and bupivacaine produce a similar pattern of sensory block. This is consistent with our finding of similar dermatomal extension (T6-L4) in both the groups till 6h of study, which regressed to L1 level after that period. Despite the presence of sensory block up to T8 level, motor block had resolved sufficiently in all patients after 6h in Group RF, lending support to the proposition that ropivacaine produces a differential nerve block at low concentrations.
In the immediate postoperative period (0h), the intensity of motor blockade was relatively more in Group RF as compared to Group BF, whereas the intensity decreased in Group RF after 1h, but this difference was statistically not significant (P > 0.05). However, a minimal motor blockade was observed in both the groups for up to 1h of our study (Bromage score < 2).
Several studies have been examining relative potencies of sensory and motor block of epidural ropivacaine versus bupivacaine. In initial studies, in volunteers comparing dilute concentrations of epidural ropivacaine (0.1%–0.3%) and bupivacaine (0.25%) suitable for postoperative analgesia, a similar sensory-block potency with decreased motor-block potency with ropivacaine was observed. This suggested a potential superiority of ropivacaine over bupivacaine for rapid patient mobilization. Some studies reported equipotency, others reported equal analgesic potency but decreased motor-block potency with ropivacaine, whereas some reported decreased analgesic potency with ropivacaine.
The number of PCEA bolus attempts and the final volume of epidural analgesic solution consumed were significantly higher in Group BF patients as compared to Group RF (P < 0.05). Previous dose/concentration ranging studies observed that the concentrations of ropivacaine and bupivacaine in the range of 0.05%–0.1% are optimal for epidural analgesia when combined with fentanyl. These combinations improve dynamic analgesia while minimizing motor block and other side effects of local anesthetics. Hodgson and Liu reported that 0.05% and 0.1% ropivacaine appear clinically equipotent to bupivacaine for analgesia and motor block when combined with fentanyl for PCEA and noted that the use of 0.05% solutions of bupivacaine and ropivacaine resulted in decreased local anesthetic use without compromising analgesia. This is also consistent with our result and the trials performed by Liu et al. and Whiteside et al., which favor preferable use of 0.05%–0.1% ropivacaine plus low-dose fentanyl solution for PCEA after lower abdominal surgery, which decreased motor block and local anesthetic consumption without altering analgesia.
A possible explanation for more PCEA bolus attempts and increased consumption of epidural solution in Group BF compared to Group RF is the difference in potency ratio (1:1.5) between the two local anesthetics when combined with low doses of fentanyl. When small concentrations are used, these two local anesthetics seemed equipotent. This is consistent with several studies. The lower volume of solution consumed with ropivacaine group provides a practical advantage, that is, the requirement of fewer containers of PCEA solution, resulting in potentially fewer administration errors and decreased costs.
Hemodynamic parameters were found to be stable in both the groups at all time points during the 24h study, except a fall in MAP at 6h in Group BF, which was found to be statistically significant (P < 0.05). Mild hypotension was seen in four patients in Group BF, whereas only one patient had significant hypotension in Group RF, which was treated with colloids and IV ephedrine (6mg) boluses.
The patients in both the groups were awake, alert, cooperative, and able to complete VAS score, except few patients in Group BF who appeared sleepy immediately and up to 6h after surgery, but this difference was statistically not significant (P > 0.05). None of the patients in the groups had respiratory depression or decrease in oxygen saturation.
The incidence of postoperative nausea and vomiting (PONV) in our patient population (especially, Group RF) was lower compared to general risk of PONV in patients undergoing major abdominal oncosurgery. This is firstly because of opioid sparing effect of regional anesthesia and secondly because of the surgical procedure (mainly hysterectomy) itself. Marginally less PONV in Group RF as compared to Group BF may be associated with less amount of consumed morphine owing to comparatively less postoperative pain in Group RF.
| Conclusion|| |
Ropivacaine (0.1%) has marginally greater analgesic efficacy, hemodynamic stability, and fewer side effects (cardiotoxicity and motor blockade) than bupivacaine (0.1%) when administered by PCEA pump for POPR after elective major abdominal oncosurgery via a vertical midline infraumbilical incision.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]