Efficacy of Periarticular Cocktail Injection in Rheumatoid Patients Undergoing Total Knee Replacement

Abstract

Background

Pain control after total knee replacement (TKR) is of primary importance to joint replacement surgeons to achieve good functional outcome post-surgery. This becomes even more challenging when these major procedures are done in immunocompromised patients like rheumatoid arthritis. Good peri-operative analgesia facilitates early rehabilitation, improves patient satisfaction, and reduces the hospital stay. The adverse effects caused by epidural analgesia or parenteral opioids can be avoided by replacing it with an analgesic cocktail locally. Our prospective study was to evaluate the benefits of a periarticular cocktail injection which was given in rheumatoid patients undergoing bilateral TKR in single sitting with respect to pain and knee motion recovery.

Methods

Sixty-four rheumatoid arthritis patients undergoing simultaneous primary total knee replacement were included in the study. A total of 128 knees were randomized either to receive a periarticular intra-operative injection containing ropivacaine, fentanyl, clonidine, cefuroxime and epinephrine (Group A) on one knee and to receive plain ropivacaine (Group B) on the opposite knee. The perioperative and post-operative analgesic regimens were standardized. All patients received the same standard analgesia protocol. Visual analog scores for pain, knee range of motion and quadriceps function were recorded on the day of surgery, first post-operative day, second post-operative day, day of discharge, and 2 weeks and 6 weeks during follow-up. The need for rescue analgesic requirement and adverse effects to the cocktail injection were also noted during the study period.

Results

The patients who received the periarticular cocktail fared better in terms of pain scores and functional recovery. Additional rescue agents used were significantly less at 6 h, at 12 h, and over the first 24 h after the surgery in group A when compared with group B. No cardiac or central nervous system toxicity was observed.

Conclusions

Periarticular cocktail injection significantly reduces the requirements for post-operative analgesia and also improves patient satisfaction, with no apparent risks, following total knee arthroplasty in rheumatoid arthritis.

Introduction

Pain in rheumatoid arthritis (RA) may be due to joint inflammation which could be augmented by central sensitization and structural joint damage. Patients with secondary arthritis eventually experience severe pain and they become physically challenged. TKR in these patients is a highly rewarding surgery but post-operative pain can be severe and unbearable [1].

Even though total knee replacement in a secondary arthritis gives an excellent outcome [2], post-operative pain management is still a challenge to the treating surgeon which may prevent patients from sleeping, ambulating, and participating in physical therapy [3, 4]. If patient is not ambulated early, it increases the post-operative complications such as pneumonia or deep vein thrombosis [5].Pain control can be achieved through different techniques, and each has its own risks and benefits. Primary aim is to control post-operative pain.

The use of periarticular injection to control pain after TKR has gained wide acceptance [6–9] as it provides analgesia locally in the surgical site with minimal systemic side effects. Along with pain control, it also maximizes muscle control, promotes rehabilitation, and decreases venous stasis. This technique is cost effective, and is easy to administer which does not require any special technical skill for administration [10].

Multimodal methods for controlling post-operative pain was first introduced and refined by Kehlet, Dahl [11] and Wall [12]. The principle of multimodal therapy is to use interventions that target several different steps of the pain pathway, allowing agents to act synergistically while requiring lower total doses of each drug. This promotes more effective pain control with fewer associated side effects [13].

Various “cocktails” have been suggested for the periarticular injections. Most include a long-acting local anesthetic along with epinephrine and other additives such as opioids or ketorolac, corticosteroids, and various antibiotics [14–17].

Our hypothesis was that the post-operative pain score would be less with a better functional outcome in patients who had a periarticular cocktail injection. The aim of our study was to investigate the efficacy of a periarticular injection in rheumatoid arthritis patients undergoing TKR and whether cocktail drugs have an advantage over plain ropivacaine.

Materials and Methods

Study design This was a prospective, double-blinded randomized study conducted at our centre between April 2016 and March 2019 which specializes in knee and hip surgeries. The study was approved by the institutional review board (IRB) on 11/03/2016 with certificate number (IEC/2016/002B). Informed written consent for the publication of clinical details, according to the declaration of Helsinki was taken from the patients. The study was registered with the title “Efficacy of Periarticular Cocktail injection in rheumatoid patients undergoing Bilateral Total Knee Replacement” before the onset of participant enrolment.

Participants Participants were recruited between April 2016 and March 2019. Eligible patients were at least 18 years of age and scheduled for bilateral TKA who was diagnosed with rheumatoid arthritis. Exclusion criteria were patients undergoing revision TKR, gross malalignment (deformity more than 40°); poorly controlled diabetic mellitus, defined as Hb A1c level above 7.0% [18]; Any contraindication for spinal anaesthesia; allergy or intolerance to one of the study drugs; regular opioid use; renal and hepatic insufficiency, ASA grade more than 4; and a prolonged QT interval on electrocardiography, patients with BMI more than 40, any associated intra-operative complications. The inclusion and exclusion criteria have been summarized in Table 1.

Table 1.

Inclusion and exclusion criteria

Inclusion criteria

1. Patients scheduled for a primary TKR diagnosed with rheumatoid Arthritis (RA)

2. Patients who are willing and able to provide written informed consent for their involvement in the study

3. Patients between 18 and 85 years of age

Exclusion criteria

1. Patients undergoing revision TKR

2. Patients with greater than 40 degrees of knee malalignment (varus or valgus)

3. Patients with any contraindications to the use of periarticular related drugs

4. Patients with chronic opioid use (defined as daily use for > 3 months)

5. Patients with advanced renal disease (defined as GFR < 30) or severe liver disease

6. Patients with an American Society of Anesthesiology (ASA) score of ≥ 4

7. Patients with poorly controlled diabetes mellitus (HbA1C > 7.0 on pre-admission testing)

8. Patients with a BMI ≥ 40

9. Any associated intra-operative complications

10. Patients with a concurrent physical condition that may require analgesic treatment during study follow-up

Randomization and blinding Randomized numbers from 0 to 99 were generated using computer software (Excel 2010, Microsoft). Randomization was done by one of the senior authors (JJP) just before the surgery and the cocktail was prepared by the author himself. The selected number was confirmed and noted by two allocating staff who were not part of the study. They were instructed not to discuss the products used with the patient and other hospital staff.

If the generated number was even, the right knee was injected with cocktail, and the left knee was injected with plain ropivacaine. If the generated number was odd, the left knee was injected with cocktail, and the right knee was injected with plain ropivacaine. The knees receiving cocktail injection was labelled as group A and those receiving plain ropivacaine was labelled as group B.

Group A injection solution consisted of ropivacaine, epinephrine, fentanyl, clonidine, cefuroxime and normal saline and group B contained ropivacaine, cefuroxime and normal saline. The volume of drugs used in each mixture has been summarized in Table 2.

Table 2.

Cocktail ingredients

Group A

Pericapsular injection total of 100 mL

1. Ropivacaine 5 mg/mL (49.2 mL)

2. Epinephrine 1 mg/mL (0.5 mL)

3. Fentanyl30 mg/mL (1 mL)

4. Clonidine 0.1 mg/mL (0.08 mg = 0.8 mL)

5. Cefuroxime 10 mL

6. Normal saline 38.5 mL

Group B

Pericapsular injection total of 100 mL

1. Ropivacaine 5 mg/mL (49.25 mL)

2. Cefuroxime 10 mL

3. Normal saline 40.75 mL

Interventions The cocktail was injected in two stages by the senior surgeon (VP) who was blinded about the cocktail which was being injected. The first stage of the procedure was done just before implantation of the components. 50 ml of the cocktail was injected into posterior capsule, medial periosteum and medial capsule, lateral periosteum and lateral capsule. The second stage of the procedure was done before the closure of capsule. 50 ml of the cocktail was injected into the extensor mechanism, synovium, anterior capsule, pes-anserine, retinaculum, periosteum, iliotibial band, collateral ligaments and finally the skin margins (Figs. 1, 2, 3).

Fig. 1.

Injection into the posterior capsule of the knee

Fig. 2.

Injection into the periosteum and gutters of the femur

Fig. 3.

Injection into supra-patellar pouch and quadriceps tendon

A 22-gauge spinal needle was used to deliver the cocktail and while delivering the injection, the surgeon ensured that the tissues were adequately penetrated. This was visually confirmed by the elevation of the injected fluid in the periosteum and the capsule. The skin margins needed the least amount of injection usually around 10 mL.

Pre- and Post-operative Medication

The pre-op and post-op medications were kept identical in all the patients. For all patients included in the study, pregabalin 75 mg and alprazolam 0.5 mg was given as pre-emptive analgesia the previous day of surgery.

An intravenous second-generation cephalosporin (cefuroxime) and aminoglycoside (amikacin) were given pre-operatively and was repeated every 12 h for the first 48 h after surgery. We gave 1 g of tranexamic acid intravenously 15 min before skin incision and was repeated after 3 h of first dose.

On the day of surgery all patients received, intravenous paracetamol 1 g 4 h after complete resolution of spinal anesthesia which was continued 8 hourly. They were also given injection pentazocine 30 mg with injection phenergan 25 mg intra-muscularly 8 h after surgery.

From the day after surgery, oral aceclofenac 100 mg and paracetamol 500 mg was administered every 12 hourly; injection paracetamol 1 gm was reduced to 12 hourly; injection tramadol 100 mg along with injection ondansetron 4 mg was reserved as rescue analgesia. Topical cold therapy was given four times a day.

All the patients were discharged on post-operative day 4. At the time of discharge, patients were given oral aceclofenac and paracetamol 500 mg every 12 hourly for 5 days. For thromboprophylaxis, all patients were given oral ecospirin 75 mg of once a day for 6 weeks, starting from the first post-operative day. The timeline of administration of various medications for pain relief has been summarized in Table 3.

Table 3.

Timeline of administration of various medications

Pre-emptive analgesia

1. Tab pregabalin 75 mgHS@ 10:00 PM

2. Tab alprazolam 0.5 mg HS @ 10:00 PM

Anesthesia and intra-operative analgesia

1. Spinal anaesthesia (4 ml of 0.5% Bupivacaine heavy + 0.5 ml of dexmetodimidne

2. Periarticular injection

Post-operative analgesia (First 24 h)

1. Injection paracetamol 1 gm IV 8 hourly

2. Injection pentazocine 30 mg +injection phenergan 25 mg IM stat

Post-operative analgesia (After 24 h)

1. Oral aceclofenac 100 mg and paracetamol 500 mg every 12 hourly

2. Injection paracetamol 1 g IV 12 hourly

3. Injection tramadol 100 mg + injection ondansentron 4 mg IM SOS (rescue analgesia)

4. Topical cold therapy

Post-operative analgesia (after discharge)

1. Oral aceclofenac and paracetamol 500 mg every 12 hourly for 5 days

Surgery and rehabilitation All patients underwent the procedure under spinal anesthesia (4 mL of 0.5% bupivacaine heavy plus dexmedetomidine 0.5 mL). The anesthetic regimen was standardized in all surgeries. All TKRs were performed by the senior surgeon (VP), using an anterior midline incision with medial parapatellar arthrotomy. Tourniquet was used only while cementing the components. Suction drain was not used in any of the patients. Posterior stabilized components (Beuchel Pappas High Flex Mobile Bearing Knee Replacement System) were used in all patients. Patella was not resurfaced in any of the patients osteophyte excision and denervation was done. Thorough synovectomy was done. The steps in surgeries were performed sequentially.

The post-operative rehabilitation regimen was the same for all the patients, and was started on first post-operative day. Suture removal was done at 2 weeks post-operatively.

Outcome Measurements

Primary outcome The assessment was done by author (NJM) who was blinded about the randomization in which they were assigned. Intensity of pain was rated using a 100 mm horizontal visual analogue scale (VAS) in 5 mm increments, in which 0 mm represented no pain and 100 mm represented extreme pain. Before surgery, all patients were instructed on how to use the VAS. Time zero was defined as the time at which spinal anaesthesia had complete resolution [19]. The VAS score at rest was recorded every 2  h from 4 to 24 h from time zero, when the patients were awake. After this 24-h time period, the VAS score was recorded every 8 h for further 72 h. All the VAS score assessments were done separately for both the knees.

Secondary outcomes The post-operative level of pain during activity was estimated on a VAS score once a day until the fourth post-operative day. The strongest pain experienced during physiotherapy on a particular day was recorded as the VAS score during activity.

Vitals monitoring included blood pressure, heart rate, and oxygen saturation. Any adverse reactions including allergic reactions, nausea, vomiting, urinary retention, or respiratory depression were also monitored till the patients were discharged.

Range of movement was measured by the author (NJM). The data were collected during the hospital stay (from day one to four after surgery) and during regularly scheduled post-operative visits (at 2 weeks, 6 weeks after surgery). The number of rescue analgesia needed was also recorded for each patient.

Any complications that occurred during the course of the trial were recorded; particular emphasis was placed on wound complications, surgical site infections, and opioid-related side effects. Diagnosis of surgical site infections was performed using the Centre for Diseases Control standardized criteria [15]. Knee society clinical rating scores [20] were collected pre-operatively and post-operatively for all patients.

Sample size Based on previous studies, we considered a 20-point decrease in the VAS score as clinically meaningful when comparing different regimens of pain control after TKA [8].

We calculated that with a sample of minimum 60 patients (30 patients per treatment group), the study would have 80% power to detect a 20-point mean decrease in the VAS score, with a type I error of 5%.

Statistical analysis Statistical analysis of the data set was performed with use of the Kolmogorov–Smirnov test (p < 0.05) for normality and subsequently a normal t test. The analyses were performed with SPSS software (version 20; SPSS). Descriptive statistics was reported as mean and standard deviation. Unpaired t test was used to test the statistical association between the intervention arm and control arm.

Results

Patients Figure 4 is a flowchart which outlines the progress of the trial. Of 70 patients (140 knees) screened for eligibility, 64 patients (128 knees) satisfied our inclusion criteria and were randomly assigned to receive cocktail injection and its control. Six patients were excluded from the study as four patients had intra-operative-associated complication-like avulsion fracture which needed cancellous screw fixation and two of them had a bone defect which needed stem and wedges.

Fig. 4.

Flowchart showing patient recruitment and progression of trial

Preoperative Variables

There were no significant differences in the preoperative knee flexion, varus and valgus deformity, flexion deformity, extensor lag in the sitting position, and Knee Society Scores between both the groups. The baseline characteristics were similar in both groups and have been summarized in Table 4.

Table 4.

Comparison of mean preoperative knee flexion, varus deformity, flexion deformity, extensor lag (EL), and knee society scores between the Group A and Group B

Side	Mean Pre-op	Mean Pre-op	Mean Pre-op	Mean Pre-op	KSS
	Knee flexion	Varus deformity	Flexion deformity	Ext-lag
Group A	110	5.5	3.2	14.5	29.8
Group B	105	6.5	2.9	16.0	30.6
P value	< 0.001	< 0.005	0.176	0.076	0.471

Pain Scores

Pain scores in Group A were less than that of the Group B during the day of surgery, first post-op day, day of discharge and till 2 weeks post-operatively (Fig. 5). At the end of 6 weeks follow-up, the pain score in both the groups were comparable and the P Value was not statistically significant as shown in Table 5.

Fig. 5.

Pain scores using visual analog scale in Group A Vs Group B

Table 5.

Pain scores using visual analog scale in group A vs group B

Time	Group A	Group B	P value
Day of surgery (DOS)	25	50	< 0.001
First post-op day (POD 1)	35	55	< 0.001
Second post-op day (POD 2)	30	50	< 0.001
Day of discharge (POD 4)	25	40	< 0.001
2 week post-op	20	30	< 0.001
6 week post-op	15	20	0.061

Mean pain score (with standard deviation and 95% confidence intervals in brackets)

Knee Flexion

There was a statistically significant difference in active knee flexion at the time of discharge and at 2 weeks post-operatively. The knee flexion was greater in the group A when compared to group B after surgery as shown in Table 6. At 6 weeks, average knee flexion achieved was 135° in group A compared to 130° in group B and the P value (0.066) was not statistically significant (Fig. 6).

Table 6.

Knee flexion (°) in both the groups

Time	Group A	Group B	P value
First post-op Day	90	80	0.046
Second post-op Day	95	80	0.033
Day of Discharge	100	90	0.036
2 week post-op	110	100	0.042
6 week post-op	135	130	0.54

Mean knee flexion (with standard deviation and 95% confidence intervals in brackets)

Fig. 6.

Range of motion in both groups at various time period

Extensor Lag/Active SLR

Active SLR was possible in 36 knees (56.25%) in group A and 24 (37.5%) knees in group B at the time of discharge. At 2 weeks post-operatively, the numbers increased to 56 knees (87.5%) in group A and 47 knees (73.4%) in group B, respectively. At 6 weeks post-operatively, active SLR was possible in all 64 knees (100%) in group A and 60 knees (93.75%) in group B as shown in Table 7 (Fig. 7).

Table 7.

Number of patients with zero extensor lag, less than 5° extensor lag (excluding those with zero EL), and 5° or more extensor lag in both the groups

Time	Group A		Group B
Discharge	Zero EL	36	Zero EL	24
	< 5° EL	4	< 5° EL	2
	> 5° EL	24	> 5° EL	38
2 week after surgery	Zero EL	56	Zero EL	47
	< 5° EL	2	< 5° EL	2
	> 5° EL	6	> 5° EL	15
6 week after surgery	Zero EL	64	Zero EL	60
	< 5° EL	0	< 5° EL	1
	> 5° EL	0	> 5° EL	3

Fig. 7.

Number of patients with zero extensor lag, < 5° extensor lag (excluding those with zero EL), and > 5° extensor lag in both the groups at the time of discharge, at 2 weeks and at 6 weeks

Rescue analgesia and complications The number of injections used as rescue analgesia during the post-operative period is shown in Table 8. The VAS scores were asked separately for both the knees and any pain scores above seventy percent the rescue analgesia was administered. This was significantly lower in the group A when compared with group B at first post-operative day (Fig. 8). There were no significant differences in the rate of complications, including wound complications and surgical site infections, between the two groups and has been summarized in Table 9. Delayed wound healing was characterized by bloody and serous discharge which was encountered in two patients in group A and 1 patient group B. Their swabs were culture negative, and their wounds healed uneventfully on repeated cleaning and dressing. There were no cases of hematoma formation clinically in either group. None of the patients included in the study incurred symptomatic DVT, and there were no cases of allergic reactions.

Table 8.

Mean number of rescue analgesia used

	Group A (n = 64)	Group B (n = 64)
On the night of surgery	0	0
Post-operative day 1	2	4
Post-operative day 2	0	2
Post-operative day 3	0	0
Post-operative day 4	0	0

Fig. 8.

Use of rescue analgesia during post-operative period

Table 9.

Complications

	Group A (n = 64)	Group B (n = 64)
Nausea on post-operative day	0	0
Nausea on post-operative day 1	1	2
Pruritis	0	0
Respiratory depression	0	0
Wound complications	2	1
Surgical site complication	0	0
Transient peroneal nerve palsy	0	0

Discussion

Post-operative pain after total knee replacement (TKR) is of primary concern to the patients and controlling the pain is a challenge to the surgeon. The reasons for post-operative pain are mainly due to bone or soft tissue injury and due to hyper-perfusion following the tourniquet release [21]. The tissue trauma exaggerates the neurological responsiveness to pain by reducing the threshold of afferent nociceptive neurons and by central sensitization of excitatory neurons. This contributes to increased sensitivity to post-operative pain [6]. Hence, a multimodal approach for post-operative pain control has been particularly effective not only in relieving post-operative pain but also in facilitating earlier rehabilitation and improving post-operative range of motion.

Systemic opioids such as morphine or fentanyl are associated with significant side effects like nausea, vomiting, drowsiness, respiratory depression, urinary retention, and constipation [28].

The most commonly used modality for controlling pain is epidural analgesia, but it is usually associated with adverse effects like spinal headache, neurogenic bladder, hypotension, respiratory depression, pulmonary hypertension, cardiac decompensation, spinal infections [22, 23]. Regional nerve blocks like continuous femoral nerve blockade, is associated with a 1.0–2.5% incidence of muscle weakness, nerve damage, and local infection, with 57% of catheters colonized at 48 h [24–27]. Femoral nerve blocks and epidural analgesia have been reported to control pain with good efficacy. However, these procedures require a well-trained physician. Sharma et al. [29] reported the rate of femoral neuropathy after femoral nerve block to be approximately 0.59%.

Thorsell et al. [30] had reported that the patient satisfaction, post-operative pain relief and mobilization were faster in patients who had undergone local infiltration in comparison to epidural anesthesia. Spreng et al. [31] reported epidural anesthesia provided better pain relief in the immediate post-operative period, whereas local infiltration anesthesia provided better pain relief after the initial 24 h.

Various studies about periarticular injection have reported promising results from various combinations of drugs such as ketorolac, ropivacaine, bupivacaine, morphine sulphate, epimorphine, methylprednisolone, cefuroxime, epinephrine, and normal saline [14–17]. Busch et al. [6] noted that patients who received a periarticular intra-operative injection containing ropivacaine, ketorolac, epimorphine, and epinephrine used significantly less rescue analgesia during the first 24 h post-operatively. The patients experienced a prolonged narcotic-free post-operative period and also a reduced parenteral analgesia post-operatively [32]. Although the periarticular injection of a combination of agents is the most important component of the multimodal approach [1], peripheral nerve blockade is also a key component [33, 34]. We deliberately did not use peripheral nerve blockade, so that we would be able to study the efficacy of periarticular injection.

In our study, we found that the level of post-operative pain at rest in first 24 h was less in group A when compared with the group B. Group A also had better results in terms of post-operative pain during activity, range of motion. Also, the need for rescue analgesia was less in the early post-operative period in group A. The rate of complications did not differ between the groups.

Our cocktail consisted of ropivacaine, epinephrine, fentanyl, clonidine, cefuroxime and normal saline. Ropivacaine is pharmacokinetically similar to bupivacaine. As ropivacaine is a longer acting local anesthetic drug with less cardiac and central nervous system toxicity [43, 44] and allows patients to tolerate larger doses, it was chosen over bupivacaine. The maximum circulating level is reached 20–30 min after injection. Although the main action of ropivacaine is to block afferent peripheral nociceptive activity, the drug has also been shown to have some anti-inflammatory properties in human mucosal cells [45].

Epinephrine helps in facilitating contraction of the smooth muscles that line the arterioles to potentially minimize intra-articular bleeding and prolong the time the agents would act locally [47, 48]. The addition of epinephrine helps to reduce the toxicity of the local anesthetic by keeping it localized to the area of injection [34].

One of the reasons for the marked difference in the pain scores between both the groups might be because of the usage of Fentanyl. Lombardi et al. [49] showed in his study that patients undergoing TKR with his cocktail mixture which comprises of bupivacaine, epinephrine, and morphine, had increased pain scores post-operatively. When fentanyl is administered peripherally, it produces the analgesic effect [50], because opioid receptors are present on peripheral nerves [50]. In addition, fentanyl has an analgesic potency 100 times greater than morphine [50].

Christensen et al. [41], reported that addition of steroids to multimodal periarticular cocktail injection only minimized the length of hospital and did not improve pain relief or early post-operative ROM. They also posed an increased risk of post-operative infection [41, 46]. Although the existing randomized controlled trials have confirmed the safety of steroids, many surgeons still hesitate to use a drug which is thought to increase the risk of catastrophic complications such as infection and patellar tendon rupture [51, 52]. Due to the above-mentioned reasons, steroids were not added to the cocktail mixture in our study.

Our study was aimed at comparing the efficacy of periarticular cocktail drugs (Group A) with plain ropivacaine (Group B) in controlling pain and enabling early functional recovery after total knee replacement. In our study, group A had significantly lower VAS on the day of surgery, the first post-operative day, on the day of discharge, and at 2 weeks after surgery when compared to group B. Furthermore, the average pain scores in group A were approximately half when compared with group B (Table 5), (Fig. 5). Functional ability in the first 24 h was also significantly better in group A. The need for rescue analgesia (Table 8), (Fig. 8) was significantly less for the remaining hospital stay as well in group A.

We found that there were significant benefits in recovery of quadriceps function and ability to do active SLR thereby showing early functional recovery in group A at the time of discharge. Furthermore, the number of patients with no extensor lag (EL) and range of active flexion (Table 6),(Fig. 6) was significantly greater in Group A at the time of discharge and at 2 weeks after surgery. This is not hard to explain, as the pain scores in the current study was consistently lower in the Group A when compared with Group B till the time of discharge.

Apart from providing pain relief and enhancing functional recovery, this mixture has the advantage that the ingredients are inexpensive and easily available and, therefore, can be used in most of the centers.

Surgical technique, including the surgical approach and the use of a pneumatic tourniquet could have an effect on early post-operative pain [35, 36]. Differences in surgical technique may also have been responsible for the conflicting results in previous studies [37–42].

The strength our study includes its double-blinded randomized, controlled design. The scores are compared between two different mixtures in the same patient undergoing bilateral TKR operated by a single surgeon in same sitting who can lucidly appreciate with clarity the pain difference with cocktail injection.

Existing literature does not give an exhaustive study of bilateral total knee replacements on rheumatoid arthritis patients done in single sitting. The study compares the results of both the knees in the same patient, where the physical therapy regime and systemic medications (including anti-inflammatories, analgesics, and antibiotics) are kept the same, thereby eliminating these confounding factors during the comparison.

Even though various cocktails have been described in the literature, our study includes ropivacaine, epinephrine, fentanyl, clonidine, cefuroxime. Steroid has been the main component in majority of the cocktails that have been described in the existing literature. Our cocktail does not include steroid, as all our patients in the study were rheumatoid arthritis as they are more susceptible to complications like infection and tendon ruptures.

The study vividly shows the efficacy of periarticular cocktail injection in rheumatoid arthritis patients undergoing TKR, which reduces the pain and thereby improves the functional recovery.

Based on this study, further work is warranted to determine the optimum composition of the analgesic combination to further enhance its value in making recovery from TKR more comfortable and the rehabilitation less arduous for the patient.

The current study has few weaknesses. Our study did not attempt at evaluating long-term clinical outcomes of the patients. The optimal concentration of the individual components of the cocktail could not be determined, and further effort is required to comment on the superiority of one component over the other.

Conclusion

The combination of an effective, technically well-delivered periarticular cocktail injection, in addition to a multimodal supplemental pain programme and the use of tranexamic acid to control bleeding has revolutionized the post-operative recovery after total knee replacement. Patient satisfaction is extremely high with multimodal approach in pain management. Enhanced pain control and early rehabilitation are desired by patients and surgeons alike. Although there are numerous methods to achieve these goals, the above combination has been found to be safe and extremely effective, with no apparent risks. This simple and inexpensive technique can significantly reduce pain and hasten functional recovery in rheumatoid arthritis patients undergoing total knee replacement.

Abbreviations

ASA

American Society of Anesthesiology

BMI

Body mass index

DOD

Date of discharge

DOS

Date of surgery

DVT

Deep vein thrombosis

EL

Extensor lag

FIG

Figure

GFR

Glomerular filtration rate

HbA1C

Glycosylated hemoglobin

IV

Intra-venous

IM

Intra-muscular

KSS

Knee Society Score

PAI

Periarticular injection

POD

Post-operative day

Post-op

Post-operative

Pre-op

Preoperative

RA

Rheumatoid arthritis

ROM

Range of motion

SLR

Straight leg raise

TKR

Total knee replacement

VAS

Visual analog score

Author Contributions

Dr Nikhil Joseph Martin (NJM): study concept and design, data collection, data analysis and writing the paper. Dr Vinod Padmanabhan (VP): study concept and design, operating surgeon and writing the paper. Dr Johny Joseph Pindis (JJP): study concept and design, reviewing the paper. The authors thank Ms. Sowbhaghya S Prabhu for her help in preparing the data analysis in this study. The authors thank Dr. Ammu S Bhaskar for her contributions in preparing the manuscript. The authors thank all the staff and management of Sudheendra Medical Mission Hospital for completing the study.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard statement

The study was approved by the institutional review board (IRB) on 11/03/2016 with certificate number (IEC/2016/002B). This study is registered under Institutional Ethics Committee ECR/884/Inst/KL/2016; Sree Sudheendra Medical Mission Hospital, Chittoor road, Cochin, 682018; Kerala, India. Ethical committee Approval: 11/03/2016. Certificate Number: IEC/2016/002B.

Informed consent

Informed written consent for the publication of clinical details, according to the declaration of Helsinki was taken from the patients.