Efficacy of Periarticular Local Infiltrative Analgesic Injection on Postoperative Pain Control and Functional Outcome in Sequential Bilateral Total Knee Replacement: A Prospective Controlled Trial in 120 Consecutive Patients

Abstract

Background

One of the drawbacks of total knee replacements (TKR) is the early postoperative pain, which affects patient satisfaction and increases the duration of rehabilitation. The present study analyzes the potency of local infiltrative analgesia and its effect on rehabilitation in bilateral sequential TKRs.

Materials and Methods

The present prospective observational study was conducted on 120 patients undergoing bilateral sequential TKR performed by a single surgeon using an anterior midline incision with a standard medial parapatellar approach. At the end of the surgery, a periarticular cocktail injection was administered to one knee, whereas the other knee served as the control. Postoperatively, patients were assessed for the pain level in each knee based on the visual analog scale (VAS) score and improvement in the range of motion (ROM). Intergroup and intragroup analyses were performed using the unpaired t test and analysis of variance, respectively. A p value of < 0.05 was considered significant.

Results

Of the 120 patients, 58% were women and 42% were men with a mean age of 62.14 ± 8.58 years. The postoperative mean VAS score was significantly lower in the test knee group than in the control knee group (p < 0.05). The postoperative mean ROM was more in the test group as compared to the control group on days 3 and 7 (p < 0.05), whereas it was comparable on day 14 (p > 0.05).

Conclusion

Periarticular injection of a drug combination in patients managed with bilateral TKRs that are done simultaneously reduces the early postoperative pain and improves rehabilitation during the first week after surgery.

Introduction

The increase in life expectancy due to advancements in medical science has led to a large elderly arthritic population who might need surgical intervention to relieve the severe pain and physical challenge posed by progressive arthritis [1, 2]. Approximately 90% of such patients exhibit improvement after total knee replacement (TKR), which thus enhances their quality of life [3]. Therefore, the prevalence of TKR is increasing daily, with a prevalence of 4.55% among adults aged above 50 years [4]. A major drawback of this surgery is early postoperative pain, which affects patient satisfaction and delays rehabilitation and mobilization of the knee joint [5, 6]. Failure of early ambulation increases the risk of complications such as pneumonia, muscle atrophy, capsular contractures, and deep vein thrombosis, which may impair the final functional outcome [7]. Although adequate analgesia can be achieved through continuous epidural anesthesia and femoral nerve block, they are associated with potentially severe side effects [8]. Therefore, multiple methods of achieving postoperative analgesia such as periarticular or intra-articular injections have been introduced for patients undergoing TKR [9–11]. Multimodal therapy is the utilization of interventions or drugs that target different steps of the pain pathway, allowing synergistic action and lowering the total required dose of each drug. This promotes effective analgesia with fewer side effects [7]. Several studies have demonstrated periarticular injection of a drug cocktail in patients undergoing TKR [3, 9]. The present study attempted to evaluate the efficacy of periarticular infiltrative injection of a specific combination of analgesics on postoperative analgesia and recovery in terms of the range of movements (ROM) in bilateral sequential TKRs.

Materials and Methods

The present study included 120 patients undergoing bilateral sequential TKR surgeries for primary osteoarthritis at our tertiary care referral center from June 2016 to Dec 2018 after receiving Institutional Ethics Committee clearance. Informed consent for study participation was obtained from the patients or their legally acceptable representatives. Patients allergic to local anesthetics, those undergoing Unicompartmental knee replacement (UKR), revision TKR, those with a stress fracture, and those in whom spinal anesthesia was contraindicated or who refused to give consent for the same were excluded from the study.

Procedure

Bilateral sequential TKRs were performed by SSM (corresponding author) under spinal anesthesia and with the utilization of a tourniquet using an anterior midline incision with standard medial parapatellar arthrotomy. A 150-mL periarticular injection was prepared using a combination of bupivacaine (0.25%, 40 mL), fentanyl (100 µg, 2 mL), clonidine (150 µg, 1 mL), cefuroxime (750 mg, 10 mL), and normal saline (0.9%, 97 mL). At the end of the surgery, this periarticular injection was randomly administered in the first operated knee, and the other knee served as the control. The injection was administered in the right knee in 60 patients, whereas it was administered in the left knee in the remaining 60 patients. The drugs were injected into the posteromedial and posterolateral capsule, quadriceps tendon and its attachments, anteromedial capsule, pes anserinus, medial soft tissue, and in subcutaneous tissues around the knee joint. During each injection, approximately 2–3 cc was injected with an interval of 1–2 cm tissue space. Approximately 50% of the drug combination was injected in deeper tissues around the joint such as the posteromedial and posterolateral capsule (Fig. 1), anteromedial and medial soft tissues (Fig. 2), pes anserinus, quadriceps muscle, and fascia, whereas the remaining 50% was injected in the superficial tissues such as the quadriceps tendon (Fig. 3) and subcutaneous tissues. A common rehabilitation protocol was followed postoperatively for each patient. The patients were assessed postoperatively for the pain level in each knee and improvement in the range of motion (ROM). The pain was assessed using the visual analog scale (VAS) at 12 and 24 hours postoperatively and every 24 hours till postoperative day 5, followed by postoperative days 7 and 14. The ROM of each knee was measured manually using a goniometer on postoperative days 3, 7, and 14. Figure 4 shows a line diagram demonstrating the sites of injection.

Fig. 1.

Injection into the posteromedial and posterolateral capsule in the region of anterior cruciate ligament origin

Fig. 2.

Injection into the a anteromedial region and b region of the medial soft tissues

Fig. 3.

Injection into the lateral suprapatellar region and quadriceps tendon

Fig. 4.

Line diagram showing sites of injection—1 and 2: posterolateral capsule, 3 and 4: posteromedial capsule, 5–8: quadriceps tendon, 9–12: subcutaneous tissue

Statistical Analysis

The data were collected using Microsoft Excel, and the statistical analysis was performed using SPSS version 20. Intergroup analysis was performed using the unpaired t test, whereas intragroup analysis was performed using the repeated measures analysis of variance. A p value of < 0.05 was considered significant.

Results

Of the 120 patients, 58% were women and 42% were men with a mean age of 62.14 ± 8.58 years. The average body mass index (BMI) was 26.54 ± 3.83 kg/m². The mean duration of right knee surgery was 62.52 ± 11.82 min, whereas that of the left knee was 64.02 ± 8.08 min, and this difference was statistically not significant (p = 0.3). Implants with rotating platforms that were posteriorly stabilized (DePuy) were used in 110 patients, posterior stabilized fixed-bearing implants (Zimmer) were used in 8 patients, and implants with rotating platforms that were posteriorly stabilized (Attune) were used in 2 patients (Table 1). The average VAS score at 6 h, 12 h, 24 h, 48 h, 3 days, 7 days, and 14 days was significantly lower in the test knee group than in the control knee group (p < 0.05). The intragroup comparison exhibited a significant progressive reduction in postoperative pain in both groups (p < 0.05) over the period from 6 h to 14 days (Table 2). 

Table 1.

Patient, surgery, and implant characteristics

Demographic details
Parameter assessed	Value
Mean age	62.14 ± 8.58 years
Number of men	50
Number of women	70
Mean height	157.6 ± 10.75 cm
Mean weight	67.54 ± 14.11 kg
Mean BMI	26.54 ± 3.83 kg/m2

Duration of surgery
Surgery side	Mean time
Right knee	62.52 ± 11.82 min
Left knee	64.02 ± 8.08 min
p value	0.3

Type of Implants
Type of Implant	Number of patients
DePuy Posterior-Stabilized Rotating Platform	110
Zimmer Posterior-Stabilized Fixed Bearing	08
Attune Posterior-Stabilized Rotating Platform	02

Table 2.

Mean VAS score in test and control groups

Assessment time	Test group	Control group	p value (intergroup)
Preoperative	8.18 ± 1.14	7.94 ± 1.28	> 0.05
6 h	6.72 ± 1.65	7.24 ± 1.73	< 0.05*
12 h	5.88 ± 1.39	6.82 ± 1.58	< 0.05*
24 h	5.16 ± 0.99	6.16 ± 1.2	< 0.05*
48 h	4.5 ± 1.29	5.28 ± 1.23	< 0.05*
3 days	3.66 ± 1.2	4.1 ± 1.38	< 0.05*
7 days	2.38 ± 0.96	2.86 ± 1.09	< 0.05*
14 days	1.58 ± 0.97	1.8 ± 0.93	< 0.05*
p value (Intragroup)	< 0.05*	< 0.05*

*Statistically significant

The preoperative mean ROM could be compared between the test group and the control group (p > 0.05). The ROM after surgery was greater in the test group in comparison to the control group on days 3 and 7 (p < 0.05). The average ROM could be compared between the two groups on day 14 (p > 0.05) (Table 3). All 120 patients were given paracetamol and diclofenac for systemic analgesia. Of these, two patients required an additional dose of tramadol, whereas two patients required a fentanyl patch.

Table 3.

Mean ROM in test and control groups

Assessment time	Test group	Control group	p value (intergroup)
Preoperative	106.8 ± 14.77	106.2 ± 16.5	0.21
3 days	70 ± 19.39	63 ± 19.9	< 0.05*
7 days	89 ± 18.21	86.8 ± 16.49	< 0.05*
14 days	100 ± 10.88	100.6 ± 12.19	0.53
p value (intragroup)	< 0.05*	< 0.05*

*Statistically significant

Discussion

In today’s times, TKR is an extremely common surgery performed in orthopedics that caters to patients with end-stage osteoarthritis or rheumatoid arthritis of the knees. It serves to enhance the quality of living of the patients by providing relief from pain and improving mobility. However, early ambulation post-surgery is delayed due to increased pain immediately following surgery which can lead to an increased risk of thromboembolic events and have a negative impact on the overall outcome of the surgery. Many patients refuse to opt for surgical treatment and continue to live with the pain of arthritis because of the fear of postoperative pain. Adequate analgesia post-surgery would assist in rehabilitation, thereby reducing the duration of hospital admission. Our present study hypothesized that a periarticular local infiltrative analgesic injection would be effective in mitigating post-surgical pain, and thus improve the functional outcomes in patients undergoing sequential bilateral TKR. In the present study, 58% of the 120 patients were women and 42% were men with a mean age of 62.14 ± 8.58 years. This may be due to the preponderance of osteoarthritis in women and the older population [12]. The mean BMI was 26.54 ± 3.83 kg/m². This finding is concurrent with the results of a numerical investigation conducted by Wang et al. where the researchers demonstrated a positive correlation between excessive weight and the incidence of TKR [13]. Although several treatment options are available for postoperative analgesia after TKR, they have severe potential limitations. Epidural analgesia is a very common analgesic modality. However, it is often associated with adverse effects such as neurogenic bladder, spinal headache, respiratory depression, hypotension, cardiac decompensation, pulmonary hypertension, and spinal infections, which are unfavorable for early rehabilitation and may increase the chances of venous thromboembolism [9, 14]. Femoral nerve block, another common analgesic modality, is associated with a 1.0–2.5% incidence of nerve damage (0.59% rate of femoral neuropathy), local infection (57% of catheters infected at 48 h), and muscle weakness [9, 15]. Additionally, these procedures are technique sensitive and require a well-trained operator. An advantage of periarticular injection is the relative ease of administration and minimum side effects. Although systemic opioids are considered to be very effective in reducing postoperative pain, their use is associated with undesirable effects that include but are not limited to sedation, vomiting, constipation, and respiratory depression. Periarticular injection of analgesics has been shown to be effective without increasing the complications that result from the use of systemic opioids given by the oral or intravenous route. Our drug combination consisted of bupivacaine, fentanyl, clonidine, cefuroxime, and normal saline. As bupivacaine is a long-acting local anesthetic drug, it allows prolonged postoperative analgesia. One of the concerns about the use of bupivacaine is its chondrotoxic effect. However, as the removal of cartilage is a part of the TKR procedure, this consideration is not of practical concern [16]. Clonidine possesses α2-adrenergic actions and has a synergistic effect on the action of local anesthetics and opioids [17]. As our drug combination contained bupivacaine and fentanyl, we added clonidine to enhance their actions. The most important advantage of local periarticular analgesia as shown in a study by et al. as well as other studies in the literature is that the consumption of opioids like tramadol and morphine sulfate is reduced post-surgery [17]. Although several studies have included steroids in the periarticular injection, adding them to the multimodal periarticular cocktail has been demonstrated to only reduce the duration of hospital stay without improving postoperative analgesia or ROM. On the contrary, it has exhibited an increased risk of postoperative infection, probably due to its immunosuppressive effect [18, 19]. Moreover, despite its safety, it has the additional risk of patellar tendon rupture. Thus, we avoided steroids in our drug combination. The addition of morphine in drug combinations does not exhibit a significantly higher postoperative analgesia than combinations without morphine and also  has potential side effects and chances of addiction [19–21]. Therefore, we did not include morphine in our combination. The mean VAS score before surgery could be compared in the two groups, while it was lesser in the test knee group than in the control knee group at 6 h, 12 h, 24 h, 48 h, 3 days, 7 days, and 14 days postoperatively (p < 0.05). This finding was concurrent with those of Sadigursky et al. and Toftdahl et al. [17, 22]. A probable reason for the difference in VAS scores between the two groups might be due to the usage of fentanyl. When administered peripherally, fentanyl exhibits a profound analgesic effect due to the presence of opioid receptors on peripheral nerves. Additionally, its potency is 100 times more when compared to morphine [9]. The mean ROM in the present study could be compared in the two groups on postoperative day 14 (p > 0.05). This finding was comparable to the findings of Badner et al. and Mullaji et al. [20, 23]. Badner et al. tested the efficacy of an intra-articular injection of bupivacaine that was given before taking the incision and after closure of the wound. They concluded that patients who had been given an intra-articular injection of 30 ml of 0.5% bupivacaine and 1:200,000 epinephrine in saline after wound closure required less narcotics in the postoperative period and had greater range of motion as compared to patients given bupivacaine before the incision and controls [20]. Mullaji et al. determined the effectiveness of periarticular infiltration of opioid, corticosteroid, and local anesthetic. They concluded that the patients in whom the infiltration had been given showed lower pain scores and greater active flexion [23]. There were no adverse effects secondary to the use of periarticular injection in our study. This finding is concurrent with the findings of other studies such as those of Ban et al. and Martin et al. [3, 10]. Ban et al. used a periarticular injection consisting of ropivacaine, ketorolac, dexamethasone, and epinephrine mixed in a sterile normal saline solution [3]. Martin et al. used a periarticular injection consisting of ropivacaine, clonidine, fentanyl, cefuroxime, and epinephrine. Periarticular infiltration is gradually becoming a part of the standard protocol for total knee replacement in many centers. One of the reasons for this is that there are no contraindications to the use of periarticular injections in total knee arthroplasty other than allergy to the medications. Moreover, when combined with preemptive analgesia, the pain control achieved with these injections is excellent [24]. Thus, the present study adds to the evidence that periarticular injections are safe when used in TKR, wherein postoperative infection and problems in wound healing are the most prominent complications. The strengths of the present study include the prospective design and the inclusion of a control group.

The limitations of our study included the relatively small sample size and a single-center design of the study that prevented the generalization of the findings. Additionally, the assessment was not blinded, leaving the study open to prejudice by the assessor. A multicenter double-blinded study with a larger sample size would further strengthen the findings of this study.

Conclusion

The periarticular infiltration of a drug combination comprising bupivacaine, clonidine, fentanyl, cefuroxime, and normal saline in patients undergoing TKR reduces postoperative pain with no incidence of side effects or complications, thereby leading to enhanced recovery and contributing to a shorter duration of stay in the hospital. Furthermore, the delivery is very simple and easy to use.

Authors’ Contributions

RK: writing—original draft, HP: investigation, SP: writing—review and editing, RP: writing—review and editing, SK: formal analysis, PK: resources. TR: validation, SM: conceptualization, methodology, validation, writing—review and editing, supervision.

Funding

This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

Authors can confirm that all relevant data are included in the article and/or its supplementary information files.

Declarations

Conflict of Interest

All authors declare that there are no conflicts of interest.

Ethical Approval

Institutional Ethical Committee Approval was obtained for the study.

Consent for Publication

Appropriate written informed consent has been taken from all the patients for inclusion in the study and publication process.