Evaluation of a multimodal pain therapy concept for chronic pain after total knee arthroplasty: a pilot study in 21 patients

Osteoarthritis of the knee is a common condition that affects approximately 10% of the general population above the age of 60 years [1, 2]. Frequently, the diagnosis is based on radiological findings. In a study of knee osteoarthritis by Kellgren and Lawrence from 1958 a prevalence of 40.7% in females and 29.8% in males aged 55 to 65 years was found [3]. However, correlations between radiological findings and clinical symptoms are only possible to a limited extent. Spector et al. determined symptomatic radiographic knee osteoarthrosis in 2.9% of women of this age range [4]. With increasing age the prevalence of symptomatic knee osteoarthrosis rises up to 40% in the group aged from 75 to 79 years [5]. Conservative therapy, like non-steroidal anti-inflammatory drug administration, joint injections, stabilizing physiotherapy and weight reduction, is the most common treatment of symptomatic knee osteoarthrosis [6]. As a result, the progress of the disease can be slowed down and symptoms can be alleviated. When conservative therapy has been exhausted, partial or complete artificial joint replacement has established as a gold standard [7]. Total knee arthroplasty (TKA) is an effective way to manage end-stage knee osteoarthritis, to relieve pain and achieve functional improvements [8‐10]. Over the years, many refinements have been made to this surgical procedure in order to improve patient outcomes, reduce postoperative complications and ultimately to enhance the patient’s life quality after TKA [2, 11]. In spite of the improvement of many aspects around TKA, there is still a group of patients who is not satisfied with the outcome. In an extensive meta-analysis of 1308 articles, 115 patient-centered pain outcomes were reported, whereof the proportion of people with an unfavorable long-term pain outcome after TKA ranged from 10% to 34% (median: 20%) [10]. The causes of these persistent complaints are manifold and often multifactorial. There are rarely clear causes, such as mechanical problems, low-grade infections, premature loosening or cement and metal hypersensitivities, respectively [12‐16]. Extensive diagnostics are also not always able to find a definite cause. Finally, many factors remain unclear. This often results in frequent conservative and operative therapies without significant improvements up to a total knee arthroplasty replacement (TKAR). Consequently, the therapy of chronic pain after TKA represents a medical challenge that requires an interdisciplinary therapy concept. The concept of multimodal pain therapy (MMPT), especially for the treatment of chronic lower back pain, is already clinically proven and well evaluated by studies [17, 18]. Therefore, it is obvious to transfer this concept to patients with chronic complaints after TKA.

The aim of this prospective pilot study was to evaluate the efficacy of a multimodal pain therapy of chronic complaints after TKA. Depending on the results of this pilot study, a prospective two-armed survey is planned for further evaluation.

In a prospective cohort pilot study 21 patients with chronic pain after TKA were treated stationary by multimodal pain therapy (MMPT) for at least 10 days. All patients with differing causes of complaints were excluded in advance. In order to safely preclude implant loosening, inlay wear or other existing mechanical complications radiographs were used. A joint infection was excluded by blood tests and knee joint puncture. In individual cases further investigations (allergy tests, nuclear medical examinations, sectional imaging, etc.) were carried out. In order to increase the accuracy of an exclusion of periprosthetic infections, a previous arthroscopy with 5 tissue samples is planned. This can also be used to confirm a suspicious diagnosis like an arthrofibrosis by means of tissue analysis.

During the planning of the study, it was discussed with the local ethics committee. Since the investigation has been assessed as an individual test of salvation, there is no provision for the ethics committee. An ethics vote is planned for the randomized follow-up study. Before the beginning of the study all patients were informed and gave their written consent to the off-label use of the medication as an individual therapeutic attempt as well as to the publication of data.

For medication, the subjects received 20 mg of prednisolone (Reduction of inflammation and pain modulatory effects), 10 mg of propranolol (influences of sympathetic tone and reflexive pain modulation) and 25 mg of amitriptyline (modulation of neuralgiform pain) once a day over a period of 25 days. After initial exclusion of contraindications for this medication daily blood glucose control as well as measurements of pulse and blood pressure were performed. In addition, patients were treated with topical ketamine (10% ketamine hydrochloride in pre-mixed PLO gel 30, MEDISCA, USA).) Ketamine hydrochloride was used as a pure substance according to the European Pharmacopoeia (Ph.Eur.). PLO gel 30 is a ready-to-use transdermal base, composed of an oily phase (lecithin and isopropyl palmitate) and an aqueous phase (Pluronic gel 30%). The advantage of this organogel is that high amounts of active ingredients can be incorporated by the preparation which can easily pass through the skin into deeper tissues.

In the course of in-patient therapy, all patients also received regular treatments in Traditional Chinese Medicine (TCM) with acupuncture, acupressure and cupping. Moreover, daily physiotherapeutic applications with passive physiotherapy, thermal applications (hot roller), reflexology, manual therapy and Kinesiotape were performed. The pain relief service was used to optimize pain therapy. Local infiltration of points of pain with local anesthetics (lidocaine 1% and bupivacaine 0,5%) was applied, too. Figure 1 describes the treatment algorithm (kind of decision tree) of the University Hospital Leipzig relating to the therapy of persistent complaints after TKA.

All patients were examined and questioned at the time of hospital admission, discharge and at their first as well as second follow-up. Knee joint mobility and stability were investigated at all examination times. In this context, the following scores were applied.

From 03/07/2016 to 07/14/2016, 21 patients were included in the pilot study. 11 of them were women (52%). The median age was 65 years (45–79 years). With regard to the median, primary TKA implantation took place 5 years ago (1–12 years). The median value of patient’s previous operations amounted 2 treatments (1–6 operations) including primary TKA. 16 patients (76%) had already received at least one change of TKA (1–3 changes). Concerning the median, the last operation has been performed 12 months (4–84 months) ago.

Moreover, the median stay in hospital was 9 days (8–14 days). The first follow-up was planned after six weeks (median: 38 days, 30–112 days) and the second one after six months (median: 8 months, 7–12 months). The first follow-up included 17 out of 21 patients (19% drop out), whereas the following one showed a drop out of 33% (14/21).

In this context, Table 1 provides an appropriate overview of patient’s specifics according to sex, age and relevant medical history. Table 2 summarizes the median values at all examinations times of each evaluation implemented by the Numerical Analog Scale, the Knee Society Score of Insall et al., the Knee Score of Ranawat and Shine and the neutral zero method (ROM), respectively. In the median, the patients reported an improvement on the NAS (7 to 5) and the Knee Society Score of Insall (pain 25 to 15) in terms of pain during hospitalization. Both markers have increased to the 2nd follow up, but have not reached the initial level again. All changes were without statistical significance. Figure 2 illustrates the development of the pain history at all examination times Fig. 3 shows the change in movability measured by the neutral zero method (ROM) and the Knee Society Score of Insall et al. Here too, the patients in the median showed an improvement in the range of motion, especially during stationary observation (92 to 105). The ROM increased to the first follow up, but then fell again for the second follow-up. All changes were without statistical significance. The same trend is also shown with regard to the functionality where the drop down to the 2 follow up was not so impressive here and the patients were stable to the level. Patient’s functional changes assessed by the relevant subscore of Insall et al. (function score) as well as the Knee Score of Ranawat and Shine are represented graphically by Fig. 4. All changes were without statistical significance.

The treatment of patients with chronic complaints after TKA is a challenging task. Therefore, an adequate therapy is only possible due to an interdisciplinary team of experienced orthopaedic surgeons with great knowledge in the field of endoprosthetics, qualified physiotherapists and pain therapists.

With the presented pilot study on multimodal in-patient therapy of chronic complaints according to TKA, the improvement of pain, function and mobility could be shown. While the results deteriorate after hospital discharge, they rebalanced during the follow-up period with no relapse to their initial level. Further prospective studies are necessary to obtain precise statements on the success prospects through the therapy plan of the University Hospital Leipzig.