ORIGINAL ARTICLE
Year : 2020 | Volume
: 4 | Issue : 4 | Page : 188--193
Comparison of analgesic efficacy of ropivacaine and levobupivacaine in ultrasound-guided transversus abdominis plane block and port site infiltration in laparoscopic live-donor nephrectomy, a double-blind randomized parallel group trial
Sandeep Sahu1, Zakia Sayeed1, Tapas Kumar Singh1, Divya Srivastava1, Aneesh Srivastava2, Dharmendra Bhadauria3,
1 Department of Anaesthesiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
3 Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Correspondence Address:
Dr. Divya Srivastava
Department of Anaesthesiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
India
Abstract
Background: Laparoscopic live-donor nephrectomy (LLDN) produces reduced donor's pain, early recovery, and a better cosmetic compared to open surgeries. We compared the analgesic efficacy of ropivacaine and levobupivacaine in unilateral ultrasound-guided transversus abdominis plane block (UTAPB) and port-site infiltration (PSI) in LLDN. Patients and Methods: The 120 donors, American Society of Anesthesiologists I-II, of either sex were randomly divided into two groups. The ropivacaine (Group-R = 60 patients given 20 ml of 0.2%) or levobupivacaine (Group-L = 60 patients, 20 ml, 0.25%) in unilateral UTAPB and 10 ml of either drug for PSI at the end of the surgery. All patients received intravenous (IV) patient-controlled analgesia pump (fentanyl) and IV paracetamol 1 g up to 48 h of study duration. Seventy-five milligram IV diclofenac was used as rescue analgesia. The duration of analgesia, time to the first requirement, and number of times rescue analgesia, total amount of fentanyl consumed and pain score Visual Analog Scale noted. Results: In UTAPB, the duration of sensory block in the levobupivacaine group was significantly longer to the ropivacaine group, 12.70 + 7.12 versus 10.55 + 6.64 h (P = 0.090), with lesser rescue analgesic requirement 37 versus 49 (of 60 patients) and lesser total fentanyl consumption 57.50 ± 53.54 mg versus 82.50 ± 65.63 mg. The first-time rescue analgesic delayed, 80.25 ± 137.78 versus 53.67 ± 79.85 min and a number of times rescue analgesic used significantly lesser in the levobupivacaine group 0.87 ± 0.84 versus 1.15 ± 0.92, with better patient satisfaction. Conclusion: Both the levobupivacaine and ropivacaine are effective in UTAPB for the management of postoperative pain after LLDN. The duration of sensory block was longer, total opioid consumption, and rescue analgesic requirement use were significantly lesser in the levobupivacaine group.
How to cite this article:
Sahu S, Sayeed Z, Singh TK, Srivastava D, Srivastava A, Bhadauria D. Comparison of analgesic efficacy of ropivacaine and levobupivacaine in ultrasound-guided transversus abdominis plane block and port site infiltration in laparoscopic live-donor nephrectomy, a double-blind randomized parallel group trial.Bali J Anaesthesiol 2020;4:188-193
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How to cite this URL:
Sahu S, Sayeed Z, Singh TK, Srivastava D, Srivastava A, Bhadauria D. Comparison of analgesic efficacy of ropivacaine and levobupivacaine in ultrasound-guided transversus abdominis plane block and port site infiltration in laparoscopic live-donor nephrectomy, a double-blind randomized parallel group trial. Bali J Anaesthesiol [serial online] 2020 [cited 2023 Mar 23 ];4:188-193
Available from: https://www.bjoaonline.com/text.asp?2020/4/4/188/299874 |
Full Text
Introduction
Adequate management of postoperative pain in any patient is a key for the early recovery after the surgery. Donor nephrectomies are cases where a normal individual goes under the knife purely to benefit another patient. Such a scenario adds to ethical and moral responsibility of the physician to take the measures to reduce pain after the surgery. Laparoscopic live-donor nephrectomy (LLDN) is a gold standard approach has reduced the plight of donor's pain to a great extent, early recovery, shorter length of stays, and a better cosmetic result compared to open surgeries.[1]
However, still with LLDN, a significant percentage of donors suffer from the postoperative pain. Pain after laparoscopic nephrectomy is due to port site instrumentation pain, 4–6 cm incision in the lower abdomen for retrieval of the kidney, visceral pain of surgical resection, and stretching due to pneumoperitoneum.[1],[2] It has been established that multimodal analgesic methods are superior for postoperative pain relief. Opioids, local anesthetics (LAs) infiltration methods, nonsteroidal anti-inflammatory drugs (NSAIDs), α2-agonists, and N-methyl-D-aspartate receptor antagonists, and abdominal facial blocks had been used for the pain management after LLDN. Although opioids provide good analgesia, they are far from being an ideal analgesic due to their unwanted adverse effects in the postoperative care unit.[3],[4]
Ultrasound-guided transversus abdominis plane block (UTAPB) will help to alleviate pain and avoid over sedation. It will also reduce nausea and vomiting due to opioids. There is the minimal risk of UTAPB. It is relatively easy, safe, and effective. UTAPB and port site infiltration (PSI) with LA as part of multimodal analgesia may be an effective way to meet the analgesic needs of LLDN. UTAPB involves the deposition of LA in the neurofascial plane between two abdominal muscles, internal oblique, and transversus abdominis. UTAPB targets the lower six thoracic and upper lumbar nerves (T6-L1) as they transverse through the plane before emerging to the abdominal wall.[5] A variety of LA are available with the varying properties and duration of action. Ropivacaine and levobupivacaine are better and more safer enantiomers of bupivacaine and their potency and analgesic efficacy has been compared before in different peripheral nerve blocks and abdominal facial plane blocks.[6],[7] However, the action of these two drugs in UTAPB for postoperative pain management after LLDN has never been compared. We intended to compare the analgesic efficacy of levobupivacaine and ropivacaine when used for unilateral UTAPB and PSI in patients undergoing LLDN.
Patients and Methods
This is a double-blind, randomized clinical trial conducted after obtaining approval from the Institutional Ethical Committee (2013-71-IP-70) and Clinical Trial Registry of India (CTRI) (CTRI/2014/05/004593, dated May 13, 2014). All participants provided written informed consent to participate in this study. A hundred and twenty patients of American Society of Anesthesiologists Grade I and II, aged 18–65 years of either sex, who volunteered as kidney donor for LLDN per the institutional protocol participated as per the Helsinki Declaration and good clinical practise guidelines. Patients with known allergy to LA and infection or skin diseases at block site, obesity, incisions that extended above the umbilicus, failure to give consent, and coagulopathy were excluded from the study.
To detect mean difference in pain duration (hours) between patients of group-R (Ropivacaine) and group-L (Levobupivacaine) [10±5 vs. 13±1.0, effect size for mean difference =0.60], at 88% power of the study and minimum two-sided 95% confidence interval, minimum required sample size in each of the two group came out to be 56. Finally, we have included 60 patients of in each group (total 120 patients) to rule out any droop out. Sample size was estimated using software G Power version - 3.1.9.2 (Düsseldorf university, Germany). One hundred and twenty participants were randomly divided into two groups as allocated as per the computer-generated random tables to either receive 20 ml of 0.2% ropivacaine (Group R = 60 patients, ROPIN®, Neon Laboratories Ltd.) or same 20 ml of 0.25% levobupivacaine (Group L = 60 patients, LEVO-ANAWIN®, Neon Laboratories Ltd.) in unilateral UTAPB and 10 ml of either drugs for the infiltration at three port sites.
An anesthesiologist not participating in the study used previously coded-sealed envelope to determine the treatment arm of the patient. He used similar syringes of 20 ml and 10 ml to prepare a total of 30 ml of drug and labeled them as “Trial Drug.” The syringes were loaded taking full sterile precautions and were placed on the sterile trolley to be used for the block. All UTAPBs were performed by one experienced anesthesiologist in both groups, who was unaware about the trial drug. During preoperative assessment, patients were explained about assessing postoperative pain on a Visual Analog Scale (VAS). They were also informed how to use intravenous (IV) patient-controlled analgesia pump (IVPCA) postoperatively.
The balanced general anesthesia was used in both the study groups. We administered IV midazolam 0.03 mg/kg, 2 ug/kg fentanyl, titrated propofol to absence of response, and facilitated endotracheal intubation with 10 mg of vecuronium. Anesthesia was maintained with oxygen air mixture and sevoflurane (1%–2%). All patients underwent laparoscopic transperitoneal donor nephrectomy using three ports all which were lateral to midline on the side of operation [Figure 1]. The surgery was performed by the same group of surgeons in similar methods. The intraabdominal pressures were kept between 10 and 12 mmHg during all the laparoscopic surgeries. Kidney was retrieved through a modified iliac fossa incision on the side of nephrectomy as described by Gupta et al.[8]{Figure 1}
At the end of the surgery, all patients received port site subcutaneous infiltration with pre-filled “trial drug” and UTAPB was given with a 5–10 MHz linear probe (Fuzifilm Sonosite, Inc., Bothell, USA) with full aseptic precaution. All the three layers of abdominal muscles were visualized above the level of iliac crest in mid axillary line. Trial drug was given under the real-time guidance, with help of a 45 mm 18G cannula stylet (BD Venflon™ pro IV cannula), in between internal oblique and transversus abdominis muscles [Figure 2]. The splitting of fascia and spread of drug were visualized and confirmed. The anesthesiologist and outcome assessor were blinded to the group allocation and drugs used. Thereafter, muscle relaxation was reversed and trachea extubated once adequate muscle strength was reached as per the protocol. They were shifted to post anesthesia care unit for further care.{Figure 2}
All patients received IVPCA with no background infusion. The pump was filled with fentanyl in the concentration of 10 mcg/ml and set to deliver 2.5 ml on demand with a lock out time of 5 min and maximum doses in 1 h was set to five. All patients received IV paracetamol 1 g 1 h before end-of-surgery and then 6 hourly up to 48 h after the operation. IV diclofenac 75 mg diluted in 100 ml given over 15 min was used as rescue analgesic if VAS increased to >3 or on patient's demand.
The duration of sensory block, time to first requirement of rescue analgesic, and total amount of fentanyl (IVPCA) consumption in first 48 h after the surgery were taken as primary outcome. Pain scores VAS was noted as stated by the patients postoperatively at 0, 1, 2, 4, 6, 12, 24, and 48 h, and number of times rescue analgesic was required over 48 h were the secondary end point. The incidence of postoperative nausea vomiting, pruritus, sedation score, and hemodynamic was assessed over 48 h postoperatively.
The statistical analysis was carried out using the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA version 20.0 for Windows). All quantitative variables were estimated using mean and standard deviations (SD). Normality of data was tested, and a variable was considered normally distributed when Z score of skewness was within ± 3.29. Since VAS scores were normally distributed student t-test was applied. Time to first requirement of rescue analgesic and total dose of fentanyl used were also compared with the Independent sample t-test. Number of times rescue analgesic was required was compared using the Mann–Whitney U-test. Qualitative or categorical variables documented as frequency and compared using the Fisher's or Chi-square test. All statistical tests were two-sided and performed at a significance level of α =0.05.
Results
The allocation of patient shown in consort diagram is shown in [Figure 3]. The demographic data are comparable in both the groups [Table 1]. The mean age was 44.38 ± 11.03 and 45.28 ± 11.00 years that was comparable in both the groups. Existing comorbidities include hypertension, hypothyroidism, and asthma, which all were optimized before the surgery.{Figure 3}{Table 1}
The duration of sensory block in Group L was significantly longer compared to Group R (12.70 + 7.12 vs. 10.55 + 6.64 h, P = 0.090). Total opioid use by IVPCA fentanyl was also significantly lower (57.50 ± 53.54 vs. 82.50 ± 65.63 mg) in Group L [Table 2]. The overall patient satisfaction on arbitrary score (good, better, and best) was better in Group L (49 vs. 41). No adverse effects were seen in 55 patients (Group L) compared to 48 patients in Group R. No patient in either group experienced sedation due to the use of fentanyl IVPCA.{Table 2}
The pain score in Group L is less than Group R; however, the difference was nonsignificant [Table 3]. Both drugs are equally effective in reducing postoperative pain management. Hemodynamic parameters such as heart rate, systolic blood pressure, and diastolic blood pressure remain comparable in both groups [Table 4].{Table 3}{Table 4}
Discussion
Various modalities have been tried to improve postoperative pain in patients with donor nephrectomy. The most commonly used regimen is IV NSAIDs such as ketorolac and intermittent opioids as required. IVPCA with opioids, epidural analgesia, LA infiltration as intraperitoneal, subfascial, or subcutaneous have all been tried.[3],[4],[5] However, all the above measures have some inherent disadvantages.
Previous studies have shown the efficacy of UTABP over placebo (saline) or local infiltration in controlling postoperative pain in patients undergoing laparoscopic nephrectomies.[9],[10],[11] However, this study have not shown any additional advantages of the UTABP over LA infiltration at the subfascial area at the site of surgical incisions, but increase in surgical time was found, because of time taken to perform block was longer to infiltration.[11] In another study, single-short unilateral UTAPB block was equally effective for the postoperative as compared to UTAPB with catheter to continuous prolong analgesia after LLDN.[12]
In this study, we found that unilateral single-short UTAPB is effective for postoperative pain management after LLDN. Even transverse abdominal plane block showed comparable analgesic effects as with the continuous epidural analgesia after LLDN, as epidural analgesia is considered the gold standard for any postoperative pain but residual motor block, chance of infection, early mobilization, and early discharge due to residual motor block are the important issues.[13]
The demographic data were comparable in both the study groups, except the one important finding that maximum were females who are voluntary donating kidney to their family members. This had been shown also in other Indian studies that donating a kidney to a spouse has been associated with great satisfaction and improved interpersonal relationships in the family.[14],[15] Our hospital is authorized government tertiary level center and following all the rules and regulation of Human Organ Transplant Act, as per the Government of India.
To provide a holistic approach to analgesia, we decided to utilize the advantages of both UTAPB and PSI during this study as compared previous studies either use UTAPB or infiltration.[9],[10],[11],[12] Two intermediate acting LA agents ropivacaine and levobupivacaine were used in this study in two separate groups. Both these drugs have been compared in various concentrations in different nerve blocks previously and found them to be equipotent with the similar duration of action.[3],[4],[5]
The present study found levobupivacaine to have superior analgesia to ropivacaine in terms of longer duration of analgesia, with reduced total opioid requirement by IVPCA and lesser number of patients requiring rescue analgesia after longer postoperative duration as compared to ropivacaine. Comparing both the drugs, the ropivacaine and levobupivacaine, various studies in other peripheral nerve blocks, had shown that levobupivacaine because of high lipophilic and vasoconstrictor properties compared to ropivacaine, had a longer duration of analgesia than that of an equivalent dose of bupivacaine or ropivacaine, as we compared and found with similar results in this study.[6],[7],[8],[9],[10],[11]
In this study, we used the similar volumes and almost equal concentrations of levobupivacaine and ropivacaine. The duration of sensory and motor nerve block as well as postoperative analgesia was longer in levobupivacaine compared to ropivacaine. The different potency ratio of levobupivacaine and ropivacaine was the possible explanation of this finding, because of difference in molarity as well as different protein binding nature of ropivacaine and levobupivacaine (90%–92% vs. 95%). Ropivacaine is about 40% less potent than racemic bupivacaine, whereas levobupivacaine has the same potency of racemic bupivacaine, so it can be said that levobupivaine may have 40% more potency to ropivacaine.[16],[17]
The potency of drug depends on the type of block, vasoconstrictor property of aminoamide LA, vascularity of the injection site, lipid solubility, and addition of epinephrine that may contribute to decreased absorption of LA into systemic circulation. This leads to prolonged nerve exposure to LA and reduced plasma levels, which lead to an increased duration of anaesthesia produced by the LA. The vasoconstrictor property depends on the inward shift of calcium ion through voltage-gated calcium channels present on cell membranes and lipid forms major component of it. The degree of lipophilicity of the LA agent (levobupivacaine is more lipophilic than ropivacaine) may have significant effects on the cell membranes, thereby changing the gating of ion channels of the calcium channel. Thus, levobupivacaine being highly lipophilic remains in contact with nerve fibers for longer duration and therefore provides longer postoperative analgesia.[16],[17],[18]
Dose of a drug is decided by striking a balance between obtaining desired clinical effects and preventing toxic effects. Wada et al. showed 20 ml of 0.25% ropivacaine when used bilaterally in ultrasound-guided rectus sheath block, none of the patients exceeded the toxic threshold of 3.2–3.6 ug/ml in blood.[19] Ishida et al. found when 40 ml of 0.25% levobupivacaine was given bilaterally in UTAPB, none of patients had toxic threshold of 2.62 ug/ml in blood.[20] To enable blinding, in this study, total 30 ml of drugs of either drug with almost equal concentration was chosen 0.25% for levobupivacaine and 0.2% of ropivacaine.
Conclusion
Unilateral, single-shot UTABP and PSI with either ropivacaine or levobupivacaine at the end of the LLDN provides effective analgesia up to 48 h post-operative period with fewer side effects. However, levobupivacaine to have superior postoperative analgesia to ropivacaine in terms of longer duration of analgesia, with reduced total opioid requirement by IVPCA and lesser number of patients requiring rescue analgesia as compare to ropivacaine.
Acknowledgment
We thank all the doctors and staff in anesthesiology, Nephrology, Urology and Renal Transplantation department, for help to conduct this study.
Financial support and sponsorship
The present study was funded by the intramural project grant of SGPGIMS, Lucknow, UP, India.
Conflicts of interest
There are no conflicts of interest.
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