Orthopedics

Feature Articles 

Effect of a Perioperative Intra-articular Injection on Pain Control and Early Range of Motion Following Bilateral TKA

Marc Fajardo, MD; Jason Collins, MD; Joshua Landa, MD; Edward Adler, MD; Patrick Meere, MD; Paul E. Di Cesare, MD

Abstract

Pain control after total knee arthroplasty (TKA) is integral in the immediate postoperative period for early rehabilitation. Numerous different methods of postoperative analgesia are available, but each has its own risk of adverse side effects. This study was performed to prospectively evaluate the benefits of an intra-articular analgesic injection in patients undergoing bilateral TKA.

Thirty consecutive patients undergoing bilateral TKA were enrolled in this prospective, randomized, controlled study. Each patient was randomized to receive (1) a perioperative intra-articular mixture of morphine, bupivacaine with epinephrine, and ketorolac in 1 knee, and (2) injectable sterile saline in the contralateral knee. Each patient acted as his or her own internal control. The pharmacologically injected knee had statistically significantly less pain immediately postoperatively when compared to the control knee and displayed significantly increased range of motion within the first week of rehabilitation.

The use of an intraoperative intra-articular injection with the above drug combination significantly reduces patient pain and increases postoperative mobility with no apparent risks following bilateral TKA.

Pain control after total knee arthroplasty (TKA) is of prime importance in the immediate postoperative period for early rehabilitation. Numerous different methods of postoperative analgesia are available, but each has its own risk of adverse side effects. Epidural/spinal anesthesia provides excellent analgesia but can be associated with postoperative headaches, intraoperative hypotension, risk of spinal infection, and delayed use of deep venous thrombosis (DVT) prophylaxis medications. Regional anesthesia carries the risk of injury to the neurovascular structures, infection, and hematoma formation. Narcotics routinely administered for pain control may cause nausea, vomiting, somnolence, respiratory depression, decreased gut motility, and urinary retention. The ability to improve patient comfort and decrease the need for systemic analgesia with an intraoperative, intra-articular injection would be a useful tool for the surgeon performing TKA.

The concept of an intraoperative, intra-articular injection of narcotics and/or anesthetics for pain control originated as pain management after arthroscopic knee surgery. Studies showed that patients’ subjective assessment of postoperative pain and the need for postoperative analgesia were significantly reduced.1-3 It was postulated that the effective postoperative pain control that was accomplished with small doses of intra-articular drugs occurred secondary to local receptor activation rather than systemic analgesia.1-3 Recent studies have applied the concept of postoperative intra-articular analgesia to TKA patients with mixed results.4-8 The majority of these studies have been confounded by variability of patient perception to pain in the postoperative period.

The goal of this study was to compare the pain relief provided by an intra-articular injection of ketorolac, morphine, bupivacaine, and epinephrine in patients undergoing bilateral TKA in a prospective, double-blind, randomized, and placebo-controlled study design so that individual patient confounding variables would be eliminated.

This study was approved by our institution’s ethical review board, and all patients signed an informed consent. Indications for surgery were tricompartmental osteoarthritis recalcitrant to conservative management. Inclusion criteria were men and women younger than 80 years who had elected to have a bilateral primary cemented TKA (they served as their own controls), normal cognition, and the ability to provide informed consent. Patients were excluded if they had a history of stroke or a major neurological deficit, rheumatoid arthritis, previous drug dependency, allergies to any of the pharmacological agents in the injection, renal insufficiency, and abnormal liver enzymes. Thirty consecutive patients undergoing bilateral primary TKAs were enrolled in the study.

No postoperative regional nerve blocks were performed. Total knee arthroplasty was performed through an anterior midline incision and either a standard medial parapatellar or a subvastus surgical approach; in all cases, both knees of the bilateral procedure had the identical surgical approach. Surgeries were performed sequentially; the order in which…

Abstract

Pain control after total knee arthroplasty (TKA) is integral in the immediate postoperative period for early rehabilitation. Numerous different methods of postoperative analgesia are available, but each has its own risk of adverse side effects. This study was performed to prospectively evaluate the benefits of an intra-articular analgesic injection in patients undergoing bilateral TKA.

Thirty consecutive patients undergoing bilateral TKA were enrolled in this prospective, randomized, controlled study. Each patient was randomized to receive (1) a perioperative intra-articular mixture of morphine, bupivacaine with epinephrine, and ketorolac in 1 knee, and (2) injectable sterile saline in the contralateral knee. Each patient acted as his or her own internal control. The pharmacologically injected knee had statistically significantly less pain immediately postoperatively when compared to the control knee and displayed significantly increased range of motion within the first week of rehabilitation.

The use of an intraoperative intra-articular injection with the above drug combination significantly reduces patient pain and increases postoperative mobility with no apparent risks following bilateral TKA.

Pain control after total knee arthroplasty (TKA) is of prime importance in the immediate postoperative period for early rehabilitation. Numerous different methods of postoperative analgesia are available, but each has its own risk of adverse side effects. Epidural/spinal anesthesia provides excellent analgesia but can be associated with postoperative headaches, intraoperative hypotension, risk of spinal infection, and delayed use of deep venous thrombosis (DVT) prophylaxis medications. Regional anesthesia carries the risk of injury to the neurovascular structures, infection, and hematoma formation. Narcotics routinely administered for pain control may cause nausea, vomiting, somnolence, respiratory depression, decreased gut motility, and urinary retention. The ability to improve patient comfort and decrease the need for systemic analgesia with an intraoperative, intra-articular injection would be a useful tool for the surgeon performing TKA.

The concept of an intraoperative, intra-articular injection of narcotics and/or anesthetics for pain control originated as pain management after arthroscopic knee surgery. Studies showed that patients’ subjective assessment of postoperative pain and the need for postoperative analgesia were significantly reduced.1-3 It was postulated that the effective postoperative pain control that was accomplished with small doses of intra-articular drugs occurred secondary to local receptor activation rather than systemic analgesia.1-3 Recent studies have applied the concept of postoperative intra-articular analgesia to TKA patients with mixed results.4-8 The majority of these studies have been confounded by variability of patient perception to pain in the postoperative period.

The goal of this study was to compare the pain relief provided by an intra-articular injection of ketorolac, morphine, bupivacaine, and epinephrine in patients undergoing bilateral TKA in a prospective, double-blind, randomized, and placebo-controlled study design so that individual patient confounding variables would be eliminated.

Materials and Methods

This study was approved by our institution’s ethical review board, and all patients signed an informed consent. Indications for surgery were tricompartmental osteoarthritis recalcitrant to conservative management. Inclusion criteria were men and women younger than 80 years who had elected to have a bilateral primary cemented TKA (they served as their own controls), normal cognition, and the ability to provide informed consent. Patients were excluded if they had a history of stroke or a major neurological deficit, rheumatoid arthritis, previous drug dependency, allergies to any of the pharmacological agents in the injection, renal insufficiency, and abnormal liver enzymes. Thirty consecutive patients undergoing bilateral primary TKAs were enrolled in the study.

No postoperative regional nerve blocks were performed. Total knee arthroplasty was performed through an anterior midline incision and either a standard medial parapatellar or a subvastus surgical approach; in all cases, both knees of the bilateral procedure had the identical surgical approach. Surgeries were performed sequentially; the order in which the knees were operated on was determined by the operating surgeon (E.A., P.M.). Preoperative randomization assigned 1 knee to the treatment group, which received an intra-articular injection of an analgesic cocktail containing a combination of 7 cc of 5 mg/10 cc morphine, 7 cc of 0.5% bupivacaine with 1:200,000 epinephrine, and 1 cc of 30 mg/1 cc ketorolac, and mixed with 15 cc of normal saline (total of 30 cc injected), and the contralateral knee into the control group, which received an intra-articular injection of 30 cc of normal saline after capsule closure, before the tourniquet was deflated at the conclusion of the TKA. The cocktail was not injected into the periarticular soft tissues or capsule. The attending orthopedic surgeon was blinded with regard to the assignment of each knee. No intraoperative drains were placed.

Postoperative pain and patient satisfaction related to each knee was assessed via a visual analog scale (VAS; range, 0 mm [no pain or completely satisfied] to 100 mm [extreme pain or completely dissatisfied] in 10-mm increments) preoperatively at 4, 18, 30, 42, 54, and 72 hours postoperatively. Patients were also evaluated daily for any signs of cardiac or central nervous system toxicity or wound complications. Postoperatively, the patient was placed on a tiered oral analgesic regimen, consisting of Vicodin (5/500) for pain rated <5, Percocet (5/325) for pain rated 6 to 8, or Dilaudid (2-4 mg) for pain rated 8 to 10. No intravenous narcotic medication (ie, patient-controlled analgesia) was administered.

The initial surgical dressings were removed on postoperative day 2, and range of motion (ROM) of each knee (flexion [active/passive] and extension [active/passive]) using a goniometer was recorded daily until the patient was discharged. All patients received low-molecular-weight heparin and sequential compression device for DVT prophylaxis. No clinically significant hematomas were observed in either group. There were no postoperative wound complications following hospital discharge in either group.

Pain scores and knee ROM arcs were compared with unpaired Student t test (P<.05) using Stata software (StataCorp, College Station, Texas). To detect significant differences in these study variables, a power analysis performed to detect 80% power required 30 patients undergoing bilateral TKA to be enrolled in the study. Study personnel were blinded during data collection.

Results

This prospective study was conducted over 18 months, from July 2007 to October 2009, during which 30 simultaneous bilateral TKAs (60 knees) were performed. The distribution of knees receiving the analgesic cocktail was equal (15 right and 15 left). Mean patient age was 63.5 years (range, 48-86 years), and mean weight was 185.62 lbs. The study group comprised 23 women and 7 men. No cardiac, central nervous system, or renal toxicity was observed. The average length of stay was 4.07 days in those who had the analgesic cocktail in the right knee and 4.10 days in those who had the analgesic cocktail in the left knee (Table). Patients who stayed >4 days (3 patients) did not show significant results in terms of pain control and ROM.

Patient Demographics

Average VAS pain scores were statistically significantly lower in the analgesic cocktail side than the control knee. The knee that had received the analgesic cocktail also had statistically significantly less pain at 4, 18, 30, 54, 78, and 90 hours postoperatively compared to the control knee (Figure 1).

Figure 1: Postoperative VAS
Figure 1: Postoperative VAS scores between the treated and control knees. Asterisks mark statistical significance (P<.05)

There were no significant differences between the preoperative ROM scores between the treatment and control knees. The treated knee had a statistically significantly increased ROM on postoperative day 4 compared to the control knee (Figure 2).

Figure 2: Postoperative VAS
Figure 2: Postoperative ROM arcs between the treated and control knees. Asterisks mark statistical significance (P<.05).

Discussion

Significant pain is experienced early in the postoperative course after TKA. The goal of this study was to determine if an intraoperative intra-articular injection consisting of morphine, bupivacaine, ketorolac, and epinephrine would reduce the immediate postoperative pain and/or increase postoperative mobility in patients undergoing bilateral TKA.

Studies on intra-articular injection of various cocktails after TKA have reported mixed results. Recent studies have shown that patients who had intraoperative analgesic injection after bilateral TKA reported using less postoperative analgesia and had relatively lower pain scores. Mullaji et al9 investigated the effects of an intra-articular analgesic cocktail (bupivacaine, fentanyl, methylprednisone, and cefuroxime) in regard to pain, knee flexion, and quadriceps function in 40 patients undergoing simultaneous bilateral computer-assisted TKA. They found that the patients treated with the analgesic cocktail showed significantly lower pain scores, significantly greater active flexion up to 4 weeks, and superior quadriceps recovery up to 2 weeks postoperatively. Andersen et al10 found that the intraoperative subcutaneous injection of ropivacaine was effective in patients undergoing bilateral TKA postoperatively. They also noted that a postoperative subcutaneous bolus administration 24 hours postoperatively did not show improved analgesia compared with the administration of placebo (saline). Badner et al11 reported their experience with intra-articular bupivacaine-epinephrine injection in 82 patients undergoing primary TKA. Their results demonstrated that patients receiving the intra-articular injection after wound closure required less postoperative narcotic medication and had greater ROM at discharge compared to both the cohort receiving placebo injection and the cohort receiving the bupivacaine-epinephrine injection at the time of surgical incision.

Lombardi et al5 reported similar beneficial effects associated with soft tissue and intra-articular bupivacaine, epinephrine, and morphine injection in 197 primary TKAs. They found that compared to a control cohort, pain levels during the immediate postoperative period were significantly lower in patients receiving the pharmacological injection. Improved pain control allowed study patients to increase early postoperative activity and avoid sedation associated with the need for rescue doses of narcotic medication. Positive results were also reported by Rasmussen et al,7 who used a 24- to 72-hour continuous intra-articular infusion of morphine plus ropivacaine; the authors demonstrated a significant improvement in pain control, ROM, speed to ambulation with crutches, and decreased hospital stay compared to patients treated with the standard postoperative treatment protocol. Busch et al8 evaluated a periarticular intraoperative injection containing ropivacaine, ketorolac, epimorphine, and epinephrine in patients undergoing TKA; patients who had received the injection used significantly less patient-controlled analgesia during the first 24 hours postoperatively. In addition, they had higher VAS scores for patient satisfaction and lower VAS scores for pain during activity in the initial postoperative period.

Not every report regarding intra-articular injection after TKA has shown positive results related to pain control and postoperative function. Ritter et al6 showed no difference in pain rating at 1, 6, 12, and 24 hours postoperatively in patients receiving intra-articular morphine and bupivacaine injection. Badner et al4 likewise found no synergistic pain relief with the addition of intra-articular morphine to a bupivacaine injection.

The current study was a prospective, double-blind, randomized, and placebo-controlled study. This study design should minimize individual variations in patient perception to pain and early functional improvements. The rationale for the analgesic cocktail was to facilitate contraction of the smooth muscle that lines most arterioles to potentially minimize intra-articular bleeding and prolong the time the agents would act locally. Steroids were avoided to minimize any increased risk of postoperative infection.12 No closed suction drains were used. Postoperative hematomas can account for increased pain with decreased motion. This study focused on pain control in the immediate postoperative period while the patient was in the hospital prior to discharge; the average length of stay was 4 days. It is unlikely that there would be prolonged effect from the intra-articular analgesic injection beyond this study’s duration. Since this study compared the results of each knee in 1 patient, the physical therapy regime would be the same for each knee, thereby eliminating that factor as a confounder. Further investigation is warranted to determine the optimal concentration of each component of the analgesic injection and the long-term outcomes of these patients.     

References

  1. Stein C, Comisel K, Haimerl E, et al. Analgesic effect of intraarticular morphine after arthroscopic knee surgery. N Engl J Med. 1991; 325(16):1123-1126.
  2. Heard SO, Edwards WT, Ferrari D, et al. Analgesic effect of intraarticular bupivacaine or morphine after arthroscopic knee surgery: a randomized, prospective, double-blind study. Anesth Analg. 1992; 74(6):822-826.
  3. Khoury GF, Stein C, Garland DE. Intra-articular morphine for pain after knee arthroscopy. Lancet. 1990; 336(8719):874.
  4. Badner NH, Bourne RB, Rorabeck CH, Doyle JA. Addition of morphine to intra-articular bupivacaine does not improve analgesia following knee joint replacement. Reg Anesth. 1997; 22(4):347-350.
  5. Lombardi AV Jr, Berend KR, Mallory TH, Dodds KL, Adams JB. Soft tissue and intra-articular injection of bupivacaine, epinephrine, and morphine has a beneficial effect after total knee arthroplasty. Clin Orthop Relat Res. 2004; (428):125-130.
  6. Ritter MA, Koehler M, Keating EM, Faris PM, Meding JB. Intra-articular morphine and/or bupivacaine after total knee replacement. J Bone Joint Surg Br. 1999; 81(2):301-303.
  7. Rasmussen S, Kramhøft MU, Sperling KP, Pedersen JH. Increased flexion and reduced hospital stay with continuous intraarticular morphine and ropivacaine after primary total knee replacement: open intervention study of efficacy and safety in 154 patients. Acta Orthop Scand. 2004; 75(5):606-609.
  8. Busch CA, Shore BJ, Bhandari R, et al. Efficacy of periarticular multimodal drug injection in total knee arthroplasty. A randomized trial. J Bone Joint Surg Am. 2006; 88(5):959-963.
  9. Mullaji A, Kanna R, Shetty GM, Chavda V, Singh DP. Efficacy of periarticular injection of bupivacaine, fentanyl, and methylprednisolone in total knee arthroplasty: a prospective, randomized trial [published online ahead of print December 21, 2009]. J Arthroplasty. 2010; 25(6):851-857.
  10. Andersen LØ, Husted H, Kristensen BB, Otte KS, Gaarn-Larsen L, Kehlet H. Analgesic efficacy of subcutaneous local anaesthetic wound infiltration in bilateral knee arthroplasty: a randomised, placebo-controlled, double-blind trial [published online ahead of print January 6, 2010]. Acta Anaesthesiol Scand. 2010; 54(5):543-548.
  11. Badner NH, Bourne RB, Rorabeck CH, MacDonald SJ, Doyle JA. Intra-articular injection of bupivacaine in knee-replacement operations. Results of use for analgesia and for preemptive blockade. J Bone Joint Surg Am. 1996; 78(5):734-738.
  12. Hunter JA, Blyth TH. A risk-benefit assessment of intra-articular corticosteroids in rheumatic disorders. Drug Saf. 1999; 21(5):353-365.

Authors

Drs Fajardo, Collins, Landa, Adler, and Meere are from the Department of Orthopedic Surgery, NYU Hospital for Joint Diseases, New York, New York; and Dr Di Cesare is from UC Davis Medical Center, Sacramento, California.

Drs Fajardo, Collins, Landa, Adler, Meere, and Di Cesare have no relevant financial relationships to disclose.

Correspondence should be addressed to: Marc Fajardo, MD, Department of Orthopedic Surgery, NYU Hospital for Joint Diseases, 301 E 17th St, New York NY 10003 (marcfaj@gmail.com).

doi: 10.3928/01477447-20110317-11

10.3928/01477447-20110317-11

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