European Journal of Cardiovascular Medicine

Total knee arthroplasty (TKA) is one of the most common and most successful surgeries being done for osteoarthritis (OA) of knee worldwide. While the surgery produces excellent results, it is still plagued by the problem of post-operative pain. Approximately, 60 % patients suffer from severe post-operative pain and 30 % from moderate pain.¹ Post TKA, heightened pain prolongs hospital stays, delays recovery and rehabilitation, and negatively impacts overall patient satisfaction.²Commonly used Epidural anaesthesia has various complications, including hypotension, headache, motor blockage, pruritus, and urine retention, which delays patient recovery.³ Peripheral nerve blocks pose a threat of neurovascular injury, bleeding, and infection.⁴ High doses of systemic analgesics such as opioids produce adverse effects like nausea, vomiting, drowsiness, respiratory depression, urinary retention, and constipation.^5,6 The use of various combinations of drugs in periarticular injection has shown promising results. A combination of drugs is used in suboptimal doses to reduce toxic effects of each while providing an efficacious pain relief in combination.⁷The study intended to evaluate the effect of periarticular cocktail injection  on post-operative pain control and rehabilitation with the use of combination of bupivacaine and adrenaline. The aim of our study is to evaluate the non-inferiority effect of intra-operative periarticular injection on patients’ pain scores and clinical outcome among patients undergoing TKA.

After taking permission from the IEC, study was conducted during October 2018 to September 2020 among the patients who are having Osteoarthritis of knee with fixed flexion deformity admitted to the Dept. of Orthopaedics, S C B Medical College. Patients having bilateral TKR, elderly >80 years,revision TKR,history of arrhythmia/cardiac complications and those not willing to give consent were excluded.Group A -patients in whom intraoperative periarticular cocktail injection was given.Group B -patients in whom no intraoperative periarticular saline injection was given.All the patients received spinal anesthesia with a combination of 0.5% bupivacaine and 0.5 mL (25 mg) fentanyl. All the operations and the cocktail injections were performed by a single surgeon using a medial parapatellar arthrotomy approach.Tranexamic acid was injected intravenously for control of blood loss starting approximately 15 minutes before tourniquet release.A periarticular cocktail injection consisting of 109 mL of normal saline,40 mL of 0.5% bupivacaine and 1 mL of adrenaline (total volume: 150 mL) was given to the knee of all the patients involved in the study. The infiltration was performed using a 21-gauge needle and syringe. The aforementioned cocktail injection was formulated by the orthopaedic surgeon. The cocktail was injected at the following 7 anatomical zones.

ZONES OF INFILTRATION

• The infiltration was performed using a 21-gauge needle and syringe. The cocktail was injected at the following 7 anatomical zones
•  Zone 1: medial retinaculum
•  Zone 2: medial collateral ligament and medial meniscus capsular attachment
•  Zone 3: posterior capsule
•  Zone 4: lateral collateral ligament and lateral meniscus capsular attachment
• Zone 5: lateral retinaculum
• Zone 6: patellar tendon and fat pad
•  Zone 7: cut ends of quadriceps muscle and tendon

Injection at zones 2, 3, and 4 were administered after making the tibial and femoral cuts and ligament balancing. At zones 1, 5, 6, and 7, the injection was administered after implant placement. After component placement and cement setting, tourniquet was released, and hemostasis was achieved before the wound was closed. No drains were used. Postoperative pain over both the knees were separately recorded by the nurse, who was blinded about the study, using a 10-point VAS at 6, 12, 24, and 48 hours postoperatively, and then, at once-daily intervals till the fourth postoperative day. The VAS consists of a 10-cm line, in which 0 indicates no pain and 10 indicates the worst imaginable pain.

Fig 1: Site of cocktail injection

Figure  1 showing the analgesic cocktail mixtu:re being injected 1: Posteromedial structures 2: Posterior capsule 3: Periosteum and gutters (Before implantation of the actual components). Postoperative range of active flexion was noted each day till the fourth postoperative day on both the knees separately by the physiotherapist, who was also blinded about the study.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. The obtained data were tabulated, coded, and analyzed using SPSS, version 20.Descriptive statistics was reported as mean and standard deviation. Unpaired t test was used to test the statistical association between the two groups. 

The clinical and demographic variables of the two groups in our study did not show any significant difference.

Table 1 : Evaluation  of  pain by vas score in  2 groups

DOS-Date of surgery, POD-Post operative day, DOD-Date of discharge

Table No.I revealed visual analogue pain score (VAS Score). All the Group A patients experienced less pain than the baseline parameters(p<0.05) following TKA. Patients in the  Group A have significantly less VAS Score than the control B Group during the post operative days POD 1, POD 2, POD3, POD7, DOD and 3 months following discharge.VAS Score was less from POD 1 to DOD and follow up after 3 months in Group A. VAS Score in Group A and Group B was 5.231.32 and 7.13 1.20 in POD1, 5.201.23 and 7.11 1.23 in POD2,4.901.26 and 6.131.31 in POD3,4.56 1.23 and 6.131.17 in POD7,3.01  1.31and 5.47 1.61 in DOD,1.451.21 and 3.151.15 in follow up after 3 months. So there is a decreasing trend in the pain and VAS score in the Group A than in Group B and this is found to be statistically significant.

Table 2 : Requirement of NSAID in post operative period

Table 2 provides information on the   dosage of requirement of NSAIDS. There was a clear trend for increased NSAIDS doses in the Control Group B post operatively in the hospital up to POD 7. NSAIDS requirement is less in Group A as compared to Group B postoperatively. NSAIDS requirement in Group A and Group B on POD1 was77.38 33.49 and 161.421.30, on POD2 was 73.8031.69 and 158.5227.30, on POD3 was 66.6623.85 and143.2331.30 respectively.The mean total hospital NSAID / Consumption on the post-operative days was significantly decreased in Group A compared to Group B.(p<0.05).

Table 3 : Post operative evaluation of range of motion in  between  2  groups

Table No 3 depicts the post-operative evaluation of range of motion in between 2 Groups. In our study on post-operative evaluation of Range of motion in between 2 Groups there  was significant difference in between the two Groups A and B as it was comparatively more in POD1, POD2 , POD3, POD7,DOD AND 3  months after follow up in Group A .The mean range of motion in Group A and Group B on POD1 was 112.21.20 and 110.21.20, on POD2 was 115.21.21 and 111.2 1.21, on POD3 was116.51.32 and 113.51.32 respectively.

Table 4: Duration of hospital stay in study subjects

Table 4 reveals the duration of hospital stay in study subjects. The mean duration of hospital stay was less in the Group A than in control Group B that is 8.020.15 days and 12.920.77 days respectively. This difference was found to be statistically significant.

Table 5: Straight leg raise time gap in hours  after TKR

Table 5 shows the SLR time gap in hours after TKR.  It was 7.404.20 hours and 22.9 2.54 hours respectively in Group A and Group B. This difference in performance was attributed to the cocktail injection in Group A and it was found to be statistically significant.(p<0.05).

During TKR, trauma to the tissues 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 postoperative pain.⁸Hence, a multimodal approach for postoperative pain control has been particularly effective not only in relieving postoperative pain but also in facilitating earlier rehabilitation and improving postoperative ROM The rationale for using the analgesic cocktail was to facilitate contraction of the smooth muscles that line the arterioles to potentially minimize intraarticular bleeding and prolong the time the agents would act locally. The component epinephrine in the cocktail is especially conspicuous in this regard. Regarding   visual analogue pain score (VAS Score) the entire Group A patients experienced less pain than the baseline parameters(p<0.05) following TKA. Patients in the Cocktail Group have significantly less VAS Score than the control B Group during the post operative days and 3 months following discharge. However in a study by Shah Vikramet al⁹ it was only in early post operative (1-4) days there was lower VAS score in Group A than in Group B. Furthermore in there study there was also no significant difference at the end of 3 months i.e.Group A and Group B.Post surgical pain delays early rehabilitation and thus negatively affects patients satisfaction rate. Several authors like Seas VW et al¹⁰, Yue DB et al¹¹ and Kwon SK et al¹², IkeuchiM et al¹³have found that steroid infiltration was more effective in reducing pain relief.Intraoperative cocktail injection of analgesia facilitates direct visualization and precise placement of the needle into the traumatized tissues and nerve endings. Furthermore the local concentration of cocktail agents within the soft tissues improved and prolonged analgesic blockage and decreased seepage from the wound. This finding was also concluded in a similar study by Pasero C et al.¹⁴Vendittoli et al¹⁶ demonstrated that the use of periarticular infiltration with multimodal drugs could result in less pain, improved functional recovery, and patient satisfaction.⁹ However, Koh et al¹⁷observed that pain reduction was significant in the immediate postoperative period, with no improvement in functional results or patient satisfaction after 48 hours. Currently, multimodal management of perioperative pain has been the most common means of reducing the incidence of persistent postoperative pain. It should be noted according to Koh IJ et al¹⁷  intra-articular analgesia has a fleeting effect and is not a substitute for other therapies after hospital discharge.Parvataneni et al¹⁵ demonstrated a reductionin the pain score at 72 hours after the operation, a decreased hospital stay, and increased satisfaction scores when compared with the control group.Vendittoli et al¹⁶ reported that perioperative periarticular infiltration with ropivacaine, ketorolac and adrenaline showed a reduction in narcotic requirements at 48 hours after the operation with minimal side effects to patients when compared to the control group.Busch et al¹⁸ reported a decreased consumption of patient controlled analgesia (PCA) at 12 hours after the operation and a lower pain score in total knee replacement patients who received a perioperative, periarticular injection with ropivacaine, ketorolac, normal saline, and epinephrine compared with patients who did not receive an injection.

The results of the current study successfully demonstrates that intraoperative multimodal cocktail injection safely provides post operative pain control and functional recovery and can be substituted for conventional pain control alternatives.

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