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 Table of Contents  
Year : 2017  |  Volume : 4  |  Issue : 2  |  Page : 70-76

Periarticular infiltration of bupivacaine versus levobupivacaine in postoperative analgesia in patients undergoing total knee arthroplasty

Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission16-Dec-2016
Date of Acceptance16-Mar-2017
Date of Web Publication12-May-2017

Correspondence Address:
Heba M Fathi
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Zagazig University, Zagazig, 44519
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/roaic.roaic_118_16

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Pain control is the key in patient’s recovery after arthroplasty. We compared periarticular bupivacaine with levobupivacaine in postoperative analgesia after total knee arthroplasty in this randomized double-blinded study.
Patients and Methods
Totally, 44 patients were randomly distributed to two equal groups. The L group received periarticular 150 mg levobupivacaine HCl, 0.25% concentration+0.3 mg of adrenaline (1/200 000 concentration) diluted in normal saline to be 60 ml.
The B group received periarticular 150 mg bupivacaine HCl, 0.25% concentration+0.3 mg of adrenaline (1/200 000 concentration) diluted in normal saline to be 60 ml. The primary outcomes were the quality of analgesia during 48 h postoperatively, using a visual analog scale score at 6, 12, 18, 24, 36, and 48 h postoperatively and cumulative opioid consumption at 24 and 48 h postoperatively. The secondary outcomes were the functional recovery of the knee and postoperative adverse effects.
There was no significant difference between the two groups as regards preoperative data. Pain control was comparable in the two groups. No significant complication was observed. There was good functional recovery in both groups with a higher mean degree of knee maximal flexion in the B group.
Periarticular levobupivacaine and bupivacaine have comparable analgesic effect in patients undergoing total knee arthroplasty.

Keywords: bupivacaine, levobupivacaine, periarticular, total knee arthroplasty

How to cite this article:
Fathi HM, Ezz GF. Periarticular infiltration of bupivacaine versus levobupivacaine in postoperative analgesia in patients undergoing total knee arthroplasty. Res Opin Anesth Intensive Care 2017;4:70-6

How to cite this URL:
Fathi HM, Ezz GF. Periarticular infiltration of bupivacaine versus levobupivacaine in postoperative analgesia in patients undergoing total knee arthroplasty. Res Opin Anesth Intensive Care [serial online] 2017 [cited 2020 Jun 4];4:70-6. Available from: http://www.roaic.eg.net/text.asp?2017/4/2/70/206151

  Introduction Top

Total knee arthroplasty (TKA) is one of the most effective treatment options for patients with end-stage knee arthritis [1]. Uncontrolled pain after TKA can lead to limited postoperative range of motion, arthrofibrosis, poor functional outcomes, and patient’s dissatisfaction [2]. Periarticular injection (PAI) has been reported to have good analgesic efficacy, it is cost-effective, and has few side effects [3],[4],[5]. Studies on PAI showed that it has promising results on pain control, patient satisfaction, morphine consumption during the first 48 postoperative hours, length of stay, and knee function [6],[7]. Bupivacaine is used to provide effective sensory block with beneficial postoperative analgesia by inhibiting the nociceptor [8]. However, there are many clinical reports of life-threatening neural and cardiac toxicity of bupivacaine after regional nerve blocks such as brachial, femoral, or scalene [9],[10],[11],[12] due to its narrow safety margin, given its high lipid solubility [13],[14].

Bupivacaine exists as a racemic solution, containing two enantiomers, R (+) dextrorotatory and S (−) levorotatory stereoisomers. Levorotatory enantiomer is more vasoconstrictive and less toxic [15],[16],[17]. Levobupivacaine, as the pure S (−) isomer, has been developed as an alternative to bupivacaine with a desirable blocking effect of racemic bupivacaine, but with a greater margin of safety. Moreover, levobupivacaine has also been reported to have advantages in terms of cardiotoxicity and central nervous system toxicity in animal and human volunteers [18],[19].

Because there is limited experience when comparing bupivacaine with levobupivacaine in periarticular analgesia after knee arthroplasty, we decided to carry out this randomized study aiming at comparing bupivacaine with its S (+) enantiomer, levobupivacaine, as regards their effectiveness, side effects, and complications.

  Patients and methods Top

This blinded randomized comparative study was conducted between January 2015 and January 2016 on patients scheduled for TKA, after approval of the Zagazig Ethical Committee and after obtaining patient’s written informed consent. The study was conducted in accordance with the Declaration of Helsinki and conformed to the Consolidated Standards of Reporting Trials guidelines [20],[21]. The included patients were between 50 and 69 years of age and of American Society of Anesthesiology physical status 1 and 2. The exclusion criteria were as follows: neurological disorders that prevent cooperation; allergy to the study drugs; renal, hepatic, or heart failure; history of myocardial infarction; peripheral vascular disease; chronic pain syndrome; and opiate abuse.

All patients received 1 g paracetamol 1 h preoperatively. Intraoperatively, patients were monitored using 5 lead ECG, pulse oximetry, and noninvasive blood pressure monitoring. Venous access was obtained by using an 18 G cannula, and then 3–5 mg midazolam was administered and 500 ml Ringer’s acetate solution was initiated.

Surgery was performed using the medial parapatellar approach with patellar resurfacing, under single-shot spinal anesthesia at L2–L3 OR L3–L4 with 15 mg bupivacaine+30 µ fentanyl ([Figure 1]).
Figure 1 Surgical approach

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Patients were numbered according to their operative date and their orders were randomized using computer-generated random numbers and assigned to two groups that were given periarticular analgesia:

  1. The L group received 150 mg levobupivacaine HCl, 0.25% concentration (Chirocaine; Nycomed Pharma AS, Elverum, Norway)+0.3 mg of adrenaline (1/200 000 concentration) diluted in normal saline to be 60 ml.
  2. The B group received 150 mg bupivacaine HCl, 0.25% concentration (Marcaine; Hospira Inc., Pfizer Inc., New York, New York, USA)+0.3 mg of adrenaline (1/200 000 concentration) diluted in normal saline to be 60 ml.

The periarticular drug combinations were injected as follows: posterior capsule (15 ml), medial capsule/synovium/periosteum (15 ml), lateral capsule/synovium/periosteum (15 ml), and subcutaneous tissue around the midline incision (15 ml) [22] ([Figure 2]).
Figure 2 Periarticular infiltration

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The anesthetist, the patients, and the staff providing postoperative care were blinded to the group assignment.

Postoperatively, patients received oral 1 g paracetamol/6 h, meloxicam (15 mg) every 24, and subcutaneous enoxaparin (40 mg) every 24 h. Nausea was treated with intravenous ondansetron (4 mg) when needed. Intravenous 2 mg morphine increments at a maximum dose of 10 mg/6 h were administered as rescue analgesia.

Walking was started soon after recovery of motor function assisted by standard adult walker and knee exercise assisted by physiotherapist on the first postoperative day. The primary outcomes were the quality of analgesia during 48 h postoperatively, using a visual analog scale (VAS) score at 6, 12, 18, 24, 36, and 48 h postoperatively and cumulative opioid consumption at 24 and 48 h postoperatively. The secondary outcomes were knee functional recovery that was assessed with walking distance, quadriceps function, and range of motion and postoperative adverse effects.

Statistical analysis

Sample size was calculated to be 18 in each group based on an expected difference of 2 mm in VAS between group mean with SD 3.2 mm [23]. This was calculated using Open Source Epidemiologic Statistics for Public Health (Open EPI) version 2.3 available at (http://www.openepi.com/OE2.3/Menu/OpenEpiMenu.htm), with a power of 90%, confidence interval 95%, and α value of 0.05. We decided to recruit 44 patients (22 per group) to account for possible study dropouts (20%) or lost data. Data were tabulated and subjected to computer-assisted statistical analysis using the statistical package for the social sciences version 18.0 (SPSS; SPSS Inc., Chicago, Illinois, USA). Continuous data were expressed as mean±SD, whereas categorical data were expressed as frequencies. Student’s t-test was used for comparing the mean of continuous data. Categorical data were compared using Fisher’s exact test. A P value less than 0.05 was considered statistically significant.

  Result Top

A total of 63 patients were assessed for eligibility. Of them, eight patients declined to participate in this study, and 11 patients did not meet the inclusion criteria; the remaining 44 patients were randomly allocated to two equal groups (22 patients in each group). After allocation, all included patients completed the study ([Figure 3]).
Figure 3 Study design flow chart

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As shown in [Table 1], no significant differences were present in preoperative patient’s characteristics ([Table 2]).
Table 1 Preoperative patient characteristics

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Table 2 Quality of analgesia in postoperative period

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As regards patients’ satisfaction, nine patients in the L group and 10 patients in the B group experienced excellent satisfaction. Six patients in each group experienced good satisfaction and five patients in each group experienced moderate satisfaction. Finally, two patients in the L group and one patient in the B group reported poor satisfaction.

Although total opioid analgesia and VAS scores during rest and mobilization were lower in the B group than in the L group, these differences were not statistically significant ([Table 3] and [Table 4]).
Table 3 Postoperative visual analog scale during rest

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Table 4 Postoperative visual analog scale during mobilization

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As illustrated in [Table 5], good postoperative function was observed in the operated limbs and no significant differences were observed in its parameters except on day 1 when the mean degree of maximal active flexion of the knee was significantly greater in the B group than in the L group.
Table 5 Functional recovery

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As shown in [Table 6], no significant difference was observed between the two groups as regards postoperative adverse effects. Side effects were few and included three cases of nausea without vomiting in the L group, whereas there were four cases of nausea with one case of vomiting in the B group. One patient in the B group experienced hemorrhage with hypotension that was controlled with transfusion of blood and fluid. One case of bradycardia in the B group was controlled with atropine. No other side effects such as persistent anesthesia, paresthesia, weakness, paralysis, restlessness, anxiety, dizziness, tinnitus, blurred vision, tremors, convulsions, drowsiness, unconsciousness, or respiratory arrest were found.
Table 6 Postoperative adverse effects

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  Discussion Top

Periarticular infiltration techniques target the joint capsule, deep tissues surrounding the collateral ligaments, and the subcutaneous tissues with wound edges [24]. Several authors had proposed the presence of opioid receptors in the synovial membrane [25],[26]. This would suggest that the tissues responsible for generating pain in the setting of TKA may be better targeted using a periarticular technique.

Various studies have described the use of PAIs of various anesthetics with improved postoperative pain control [23],[27],[28], but the comparison of the effect of levobupivacaine and bupivacaine injection in this site has not been discussed before in the literature.

Vendittoli et al. [29] reported that the intraoperative PAI of analgesia allowed direct visualization and accurate placement of the injection into the injured tissues around nerve endings. In addition, the entrapment of the medication within the soft tissue enhanced and prolonged the analgesic blockade, and decreased the leakage from the wound [29].

Perret et al. [30] compared patient outcomes after periarticular and intra-articular local anesthetic infiltration techniques in TKA and reported a statistically significant decrease in the VAS scores of patients in the periarticular group when compared with the intra-articular group during the first 24 h postoperatively.

In this study, we compared postoperative analgesia of single-dose periarticular bupivacaine with that of pure S (−) isomer Levobupivacaine.

Single periarticular infiltration was proven to reduce total consumption of opioid for 48 h [31]. The benefit of intra-articular catheters to provide supplementary dosages of local anesthetic in the postoperative period is unproven. In addition, catheter placement increases the risk for infection [32].

In our study, the quality of analgesia was comparable in both groups. No significant differences in VAS or opioid consumption were observed, although the two parameters tend to be lower in the bupivacaine group.

Although an in-vitro study of frog sciatic nerves showed that R-bupivacaine is more potent compared with S-bupivacaine [33], the nonsignificant difference in the quality of analgesia in our results is in agreement with those obtained from other in-vivo clinical peripheral nerve blocks such as axillary brachial plexus block [34], sciatic nerve block [35], mandibular blocks for lower third molar surgery (inferior alveolar nerve block, lingual nerve block, and buccal nerve block) [36], supraclavicular block [37], and intra-articular block [38].

It should be noted that the concentration of levobupivacaine (chirocaine, Nycomed Pharma AS) is denoted on the drug label as the concentration of the base of the molecule and not as the concentrate of the hydrochloride of the molecule, as is the case with racemic bupivacaine. Thus, an ampoule of levobupivacaine contains 13% more molecules of local anesthetic than an ampoule of racemic bupivacaine of the same concentration [39]. Therefore, the anesthetic intensity of levobupivacaine that was comparable to bupivacaine intensity is the consequence of slightly increased levobupivacaine concentrations, not the result of its potency.

When considering the duration of anesthesia, both anesthetics showed long-acting effect without a significant difference in the time to the first request of analgesia. It was 14.5±7 in the L group and 15±7.1 in the B group. Other previous studies that examined these two drugs in different sites also corroborate this finding. Cox et al. [40] found that the sensory block duration in supraclavicular brachial plexus block was ∼14, 17, and 15 h with 0.25 and 0.5% levobupivacaine and 0.5% bupivacaine, respectively. Liisanantti et al. [34] detected the mean sensory block duration of 17.8±7.2, 17.1±6.5, and 15±5.4 with bupivacaine, levobupivacaine, and ropivacaine, respectively, in axillary brachial plexus block. Ilham et al. [37], also in supraclavicular block, reported that the duration was 16.61±8.05 h with bupivacaine and 14.37±7.27 h with levobupivacaine. In the three previous studies, there was no significant difference detected between the duration of levobupivacaine and bupivacaine, which was consistent with our result.

Periarticular infiltration in the current study helps early mobilization and good postoperative functional recovery with better active knee flexion in the bupivacaine group on first day. This may be attributed to the tendency of better pain control in this group that enables better knee movement. The differential block of levobupivacaine with its less motor effect in comparison with bupivacaine showed in intrathecal [41] and extradural anesthesia [42] was not illustrated in this study because of the absence of motor block in periarticular analgesia [43],[44] as the level of PAI is distal to the level of motor innervations supplying quadriceps muscles and the posterior muscle of the thigh (that act as knee extensors and flexors, respectively). Other studies demonstrated that this technique has several advantages over traditional methods as the analgesia affects only the surgical area and causes limited interference with the muscle strength, reduces pain, and improves mobilization after TKA [32],[45].

Compared with bupivacaine, levobupivacaine appears to have a wider margin of safety in terms of cardiovascular and central nervous system adverse effects when used in large doses [46],[47]. However, in this study neither bupivacaine nor levobupivacaine showed perioperative complications. The addition of epinephrine to the injection as in case of our study helps in reducing the toxicity of the local anesthetic by keeping it localized to the area of injection [48]. Lombardi et al. [27] found no perioperative complications directly related to the injection of a combination of bupivacaine, epinephrine, and morphine.

Karaoglu et al. [49] were able to demonstrate diminished blood loss after the release of the tourniquet when epinephrine was present in the injection; this was also demonstrated in our study.

  Conclusion Top

In periarticular infiltration, levobupivacaine has a comparable analgesic effect to bupivacaine. It can be used as an alternative to bupivacaine in postoperative periarticular analgesia after TKA. Further studies are recommended in other American Society of Anesthesiology groups.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3]

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


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