Feasibility Study of Combined Peripheral Nerve Block and Physiotherapy for CRPS

A Novel Treatment Approach to Complex Regional Pain Syndrome (CRPS): A Feasibility Study of Combined Peripheral Nerve Block and Physiotherapy

Chronic pain is a debilitating condition affecting 1 of 5 Canadians and costs over 40 billion in healthcare and loss of productivity each year. Since its prevalence is increasing, especially as the population ages, effective low-cost treatment is key to reduce impact of chronic pain on patients' quality of life and on healthcare cost. Due to the complexity of chronic pain and differences between the multitudes of pain conditions, developing effective treatments is challenging. This is especially true for Complex Regional Pain Syndrome (CRPS). CRPS is characterized by severe pain out of proportion to tissue trauma, with local autonomic and inflammatory changes resulting in inability to work, depression, sleep disorders, and suicidal ideation. Although its prevalence is low in Canada, CRPS is considered one the most debilitating and least understood pain conditions. As most current treatment options have low evidence of effectiveness, there is no definitive treatment available and most often, patients are struggling to maintain an acceptable quality of life. Thus, there is a pressing need to identify new and improved treatments for adults with CRPS. An early hypothesis of CRPS pathophysiology posited that sympathetic nervous system over-activity led to many of the signs and symptoms of CRPS. As such, sympathetic nerve blocks, including stellate ganglion and lumbar sympathetic blocks, have been repeatedly investigated as a potential treatment of CRPS, but a recent meta-analysis suggests that these blocks provided no benefits for those suffering with CRPS. Newer evidence suggests that a peripheral microvascular dysfunction may underlie CRPS pathophysiology. However, no clinical trials have investigated the efficacy of a treatment targeting this peripheral pathway. The goal of this project is to assess the efficacy of a single-shot axillary brachial plexus block plus physiotherapy as a novel treatment protocol for CRPS. Our primary hypothesis is that providing a brachial plexus block in conjunction with a physiotherapy program would be superior to physiotherapy alone in treating pain and function in CRPS. Since this is a novel treatment protocol for CRPS, the purpose of our proposed study is to determine the feasibility of conducting a fully powered clinical trial.

Chronic pain is a debilitating condition affecting 1 of 5 Canadians and costs over 40 billion in healthcare and loss of productivity each year. Since its prevalence is increasing, especially as the population ages, effective low-cost treatment is key to reduce impact of chronic pain on patients' quality of life and on healthcare cost. Due to the complexity of chronic pain and differences between the multitudes of pain conditions, developing effective treatments is challenging. This is especially true for Complex Regional Pain Syndrome (CRPS). CRPS is characterized by severe pain out of proportion to tissue trauma, with local autonomic and inflammatory changes resulting in inability to work, depression, sleep disorders, and suicidal ideation. Although its low prevalence (X%1 in 5000) in Canada, CRPS is considered one the most debilitating and least understood pain conditions. As most current treatment options have low evidence of effectiveness, there is no definitive treatment available and most often, patients are struggling to maintain an acceptable quality of life. Thus, there is a pressing need to identify new and improved treatments for adults with CRPS. An early hypothesis of CRPS pathophysiology posited that sympathetic nervous system over-activity led to many of the signs and symptoms of CRPS. As such, sympathetic nerve blocks, including stellate ganglion and lumbar sympathetic blocks, have been repeatedly investigated as a potential treatment of CRPS, but a recent meta-analysis suggests that these blocks provided no benefits for those suffering with CRPS. Newer evidence suggests that a peripheral microvascular dysfunction may underlie CRPS pathophysiology. However, no clinical trials have investigated the efficacy of a treatment targeting this peripheral pathway. Current evidence of the efficacy of peripheral nerve block in treating CRPS are mostly derived from small case studies involving cost- and labour-intense regimens. The goal of this project is to assess the efficacy of a single-shot axillary brachial plexus block plus physiotherapy as a novel treatment protocol for CRPS. Our primary hypothesis is that providing a brachial plexus block in conjunction with a physiotherapy program would be superior to physiotherapy alone in treating pain and function in CRPS. Since this is a novel treatment protocol for CRPS, the purpose of our proposed study is to determine the feasibility of conducting a fully powered clinical trial. The specific aims of the feasibility trial are to assess: 1) the capacity (recruitment and staffing) required for conducting a fully powered trial, 2) the design of the novel treatment protocol, and 3) the patient response to treatment and trial protocol. Statement of Relevance The incidence of CRPS in the US is estimated to be 5.4-26.2 per 100,000 person-years 3. Although unknown, the incidence of CRPS in Ontario is likely similar considering similar prevalence of chronic pain with the US. Like others, Ontarians living with CRPS, is unknown, it is known to be have a severely debilitating symptoms, leading to decreased very poor quality of life and substantial lost productivity, which can be long-term if not quickly and properly treated. Historically, proposed treatments have been variable, resource intensive and results have been mixed. Therefore, specialized pain clinics in Ontario and across Canada are struggling to provide effective and quality care for this patient population. To date there is no definitive treatment for CRPS, thus, pain specialists have no other choice to trial several treatment options to possibly find one beneficial for their patients. By testing the effectiveness of providing a single shot brachial plexus block following by physiotherapy, on an outpatient basis, with the combination of home-based structured physiotherapy, the investigators hope to define a reproducible, outpatient, effective treatment for CRPS. If the investigators can demonstrate superiority of a brachial plexus block with physiotherapy over physiotherapy alone, the investigators will be laying the groundwork for further research into not only a new treatment protocol of CRPS that is feasible and scalable for pain clinics in Ontario and around the world but also translating animal models of CRPS pathophysiology to humans

Participants who are randomized to the experimental group (EXP arm) will receive a single-shot axillary brachial plexus block with bupivicaine 0.25% at the Kingston Health Sciences Centre Chronic Pain Clinic (KHSC-CPC). Prior to treatment, the physiotherapist will perform an initial assessment physical exam for clinical purpose (i.e., independent from study assessments). Under the brachial plexus block, the physiotherapist will perform manual therapy. The patient will then complete a 6-week specialized home exercise program, including graded motor imagery.

Participants who are randomized to not receive a block (CON arm) will also return to the KHSC-CPC for an independent assessment by the physiotherapist, followed by manual therapy (not under anesthesia), and then will complete the same 6-week specialized home exercise program, including graded motor imagery.

Participants will receive a single-shot axillary brachial plexus block. For the procedure, a 22g or larger peripheral intravenous cannula will be placed, and skin will be sterilized with chlorhexidine. Using aseptic technique, the anesthesiologist will anesthetize the skin and tract with 5cc of 1% lidocaine using a 25g 1.5" needle. After this, a 50mm or 100mm Pajunk needle will be guided under ultrasound with an in-plane technique to anesthetize the median, ulnar, radial, and musculocutaneous nerves. Identification of the axillary artery, vein and surrounding vessels will be done to ensure an intravascular injection is avoided. Once proper location is confirmed, the anesthesiologist will inject 1.5mg/kg (lean body weight) of 0.25% bupivacaine, in divided doses, after negative aspiration. Participants in the EXP arm and the CON arm will complete the same physiotherapy program.

Participants in the EXP arm and the CON arm will complete the same The physiotherapy program which will include manipulation under anesthesia (MUA) immediately following an initial visit (with or without block confirmation to break up adhesions, possibly overcoming microvascular dysfunction). After the MUA session, participants will take part in a specialized 6-week home exercise program (HEP). This 6-week program which will include graded motor imagery. During each session, the physiotherapist will work with the participants to increase ROM and limb function using manual therapy, stretching, and strengthening exercises specific to the affected joint(s)) and most importantly using GMI. At the end of each session, the physiotherapist will prescribe exercises to complete at home.

Assess the ability to recruit 60 patients (30 per arm) to complete the study protocol Protocol data: Attrition (with reasons) will be monitored by the research coordinator. Data completeness will be computed from data entered from surveys and electronic diaries. Treatment compliance data (visit attendance and average hours/day of home exercise completed weekly) will be collected. Staff time will be monitored using logs by each team member (e.g., physician, physiotherapist, blind assessor, nurses). Patient satisfaction: A custom patient satisfaction questionnaire will also be completed with post-treatment clinical assessment questionnaire to capture patients' impression of the study protocol (e.g., time commitment, treatment length).

Inclusion Criteria: Aged 18 years or older Meets the Budapest criteria for CRPS of the upper extremity Able to consent to treatment. Exclusion Criteria: Allergy to local anesthetic Allergy to chlorhexidine Infection at site of injection Previous treatment of current CRPS with a regional anesthetic technique within 6 months Unable to tolerate regional anesthesia or physiotherapy Another pain condition that affects the same limb Patient refusal or inability to consent.