Combined Intra-articular Shoulder Injection and Stellate Ganglion Block in Chronic Post-mastectomy Shoulder Pain
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms; Shoulder Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      Background and Purpose: Adhesive capsulitis of the shoulder is commonly found in patients
      after breast cancer treatment. We aimed to determine the effectiveness of combined shoulder
      joint intra-articular injection of platelet rich plasma (PRP) with stellate ganglion block
      (SGB) with ketamine &bupivacaine injection as a new technique for frozen shoulder (FS)
      management after mastectomy.

      Methods: Sixty four patients with chronic post-mastectomy shoulder pain and stiffness were
      randomly allocated into one of two groups: group A; ultrasound guided SGB (1 ml ketamine in a
      dose of 0.5mg/kg plus 5ml bupivacaine 0.5% in total volume 10 ml) and group B; ultrasound
      guided SGB plus posterior approach shoulder injection with PRP. Visual analogue score (VAS)
      at rest and at shoulder movement, range of motions (ROM) of shoulder and disability of arm,
      shoulder and hand (DASH) questionnaire were recorded.
    

Detailed description: 
      Introduction:

      Pain after breast surgery is a significant complication and can persist for several months up
      to years.The most common sites for pain localization are the axilla, medial upper arm and or
      lateral / anterior chest wall. Pain can be severe enough to cause long-term disabilities
      leading to shoulder adhesive capsulitis (frozen shoulder) or complex regional pain syndrome.
      Of course, this could also interfere with daily activities and sleep leading to negative
      influence on the quality of life of the affected women. Scar formation, protective posture
      and tension of the soft tissue after surgery can also cause alteration of the shoulder girdle
      alignment and immobility.

      Adhesive capsulitis of the shoulder is commonly found in breast cancer patients with a
      prevalence can be as high as 86%.Adhesive capsulitis of the shoulder joint is one of the main
      producers of Post-mastectomy chronic shoulder pain syndrome , the shoulder joint becomes
      tight due to capsular inflammation resulting in painful and global ROM restriction. Frozen
      shoulder management has focused around prolonged courses of physiotherapy to maintain
      shoulder mobility. Corticosteroids and anti-inflammatory medications are also considered as
      adjuvant therapies in reducing pain and inflammation.

      The stellate ganglion is a nerve bundle related to the sympathetic nervous system providing
      sensation to the upper body. It is present on either side of the trachea at the 7th cervical
      vertebrae. The stellate ganglion has second and third order neurons that modulate neuropathic
      pain to the central nervous system and body temperature. The stellate ganglion block (SGB) is
      mainly indicated for management of chronic neuropathic painful disorders of the head and
      neck, upper limb, and upper chest by reducing levels of nerve growth factor leading to a
      decrease in norepinephrine level that plays a fundamental role in pain transmission in these
      cases. Ketamine enhances the effect of sympathetic blockade with relief of pain, ischaemia
      and maintains circulation. And so, ketamine is a useful adjuvant to STGB and it clarify the
      need of permanent destruction of the ganglion by chemical/ radiofrequency neurolysis in
      patients with peripheral vascular disease.

      Recently, platelet-rich plasma (PRP) have been used in treatment of many soft tissue
      disorders with positive results being rich in several growth factors and other cytokines that
      can stimulate healing of soft tissues and joints.

      In current study, we aimed to clarify the effectiveness of combined intra-articular PRP
      injection in shoulder joint with SGB over SGB alone in the challenge of management of
      post-mastectomy chronic shoulder pain.

      Patients and methods:

      Study design and participants Our study was a randomized controlled double-blind trial
      conducted in Anesthesia Department of Medical Faculty and Pain Clinics of Mansoura Oncology
      Center, Egypt during the period from August 2017 till April 2018. The study was accepted by
      Institutional Research Board of Mansoura University (Code No: R∕ 17.08.44) and followed the
      2008 Helsinki declaration ethical standards.

      Seventy patients were assessed for eligibility. Six patients were excluded from the study
      (four did not meet the inclusion criteria and two declined to participate in the study)
      (Figure 1). Sixty four patients were included with age of 18 to less than 65 ys who showed
      post-mastectomy shoulder pain.

      Exclusion criteria were patient refusal to participate, Patients with acute shoulder pain
      (trauma, acute postsurgical pain), secondary adhesive capsulitis (prior surgery or
      non-surgically induced states of shoulder affection by adhesive capsulitis), hypersensitivity
      to amide local anesthetics, general contraindications to SGB and cardiac and hepatic, renal
      or respiratory failure. Written informed consents were obtained from individual participants
      included in the study.

      Sample size It was assessed using G-power analysis. Assuming α (type I error) = 0.05 and β
      (type II error) = 0.2 (power = 80 %) yielded a total sample size of 70.

      Randomization Each patient was assigned in a double-blinded manner to one of two groups.
      Group A (n=32) patients were subjected to ultrasound guided SGB using 1 ml ketamine in a dose
      of 0.5mg/kg plus 5ml bupivacaine 0.5% in total volume 10 ml.[9] While group B (n=32) patients
      were subjected to ultrasound guided SGB using ketamine and bupivacaine in the same dose as
      group A plus posterior approach shoulder injection with PRP.

      An individual not involved in the patient care or data collection randomly assigned the
      patients using Research Randomizer program into two blocks; each of block size 32 was also
      randomized using two lists of random numbers. Investigators were not allowed to know
      randomization codes and block size until all calculations and measurements had been entered
      into the database for all patients. All medical caregivers, investigators and patients were
      blinded to group allocation. One hour before the injection procedure of an enrolled patient,
      a nurse (not otherwise participating in the study) opened a sealed opaque envelope containing
      group allocation, and then filled the assigned drug injection for each patient according to
      the protocol of randomization. All data were entered in the database before entering the
      codes of randomization. The principles for intention-to-treat analysis were followed.

      Level of evidence:

      Level IV, clinical study

      Technique Management and Equipment:

      All suitable resuscitation drugs (eg. atropine and adrenaline) and equipment's were available
      including lipid emulsion for local anesthetic toxicity, endotracheal tubes of different
      sizes, ambo bag, and ventilator. Under strict aseptic technique for place, patients, and
      instruments, the different blocks technique done in the operative theater with IV access in
      place, O2 Mask 6L/minute, and full basic monitoring (Noninvasive Blood Pressure Amplifier,
      pulse oximeter, and ECG) attached, then all patients in this study were monitored throughout
      the procedure and up to one hour after the block performance.

      Stellate ganglion block technique The anterior para-tracheal approach C6 was done. The
      patient's neck was extended using a pillow under the shoulder while lying in a supine
      position aiming to keep the esophagus and the transverse process away from each other. Also
      the patient was asked to open mouth slightly to make the neck muscles more relaxed. Under
      complete aseptic technique, a linear probe (5-10 MHz) of Siemens Acuson P300 ultrasound
      machine was initially placed at the cricoid cartilage level. The location of C6 transverse
      process was determined by the prominent anterior tubercle (Chassaignac's tubercle). Placement
      of the ultrasound transducer helped to retract the sternocleidomastoid muscle and carotid
      sheath laterally and the pressure applied by the transducer reduced the distance between the
      tubercle and skin and to depress the lung dome to avoid occurrence of pneumothorax. A typical
      sonographic appearance at the C6 level included the anterior tubercle and transverse process
      of C6, longus capitis muscle, longus colli muscle (LC), carotid artery, and thyroid gland. We
      inserted a 22-gauge needle and directed towards to the Chassaignac's tubercle then redirected
      infero-medially towards the body of C6 until reach out of LC muscle while still staying
      within the prevertebral fascia (figure 2). After negative aspiration for blood and
      cerebrospinal fluid, ultrasound guided injection of 1 ml ketamine in a dose of 0.5mg/kg plus
      5ml bupivacaine 0.5% in total volume 10 ml 10ml volume was used before in a previous study,
      and was injected in divided doses (injectate volume of 10 ml used to ensure full ganglion
      blocked and effective spread of the anesthetic agents at the area of the lower cervical
      sympathetic chain) (figure 3). The solution was allowed to pass caudally toward the stellate
      ganglion by raising the head of the patient's bed. We confirmed the success of block by the
      development of Horner's syndrome at side of injection which included ptosis, myosis, facial
      anhydrosis, enophthalmos and nasal congestion.

      Regulations for PRP Preparation:

      At the time of treatment, PRP was obtained from a sample of patient's blood. Thirty ml venous
      blood was drawn to yield 3-5 cc of PRP. Citrate dextrose A (an anticoagulant) was added to
      prevent platelet activation prior to its use. Preparation of PRP was done by double
      centrifugation process; an initial centrifugation to separate red blood cells followed by a
      second centrifugation to concentrate platelets. The whole blood was initially collected in
      tubes containing anticoagulants. At the initial centrifugation step, whole blood separates
      into three layers: an upper layer that contains white blood cells and platelets, an
      intermediate thin layer (buffy coat layer) that is rich in white blood cells, and a bottom
      layer that consists mostly of red blood cells. For PRP production, both superficial buffy
      coat and upper layers were transferred to an empty sterile tube. Then the second
      centrifugation step was done and should be adequate to help in soft pellets formation
      (erythrocyte platelets) at the bottom of the tube. We removed the upper portion of the volume
      (platelet-poor plasma). Pellets were homogenized in lower third (5 ml of plasma) to produce
      PRP.

      Posterior approach shoulder injection techniques:

      The patient was placed in either the lateral decubitus or sitting position with the
      ipsilateral hand placed on the contralateral shoulder. The ultrasound probe (frequency 6-13
      MHz) was placed just caudal to the acromion over the infraspinatus tendon. The important
      anatomical points to identify were humeral head, infraspinatus tendon, labrum, and joint
      capsule. The posterior approach target was between the cartilage of humeral head underneath
      the capsule and the free edge of labrum. Once the target was obtained, we inserted a 22 gauge
      needle from lateral to medial direction with in-plane technique (figure 3) then injected PRP.

      The two groups were asked to do some stretching exercises at home as finger walk, cross body
      reach and outward and inward rotations. The patients were explained how to do these exercises
      and warm up the shoulder before performing the exercises by moist heating pad for 10-15
      minutes.

      Outcome Variables Primary outcome: Visual analogue score (VAS) was done at rest and at
      shoulder movement before injection, one, two and three months after injection. VAS was
      explained to the patients during assessment as 0 equal no pain and 10 equal worst imaginable
      pain. Shoulder mobility was assessed while the patient was sitting using goniometry.
      Secondary outcome: 1-ROM was measured in degrees in five position (extension, flexion, and
      abduction, internal and external rotation) before and one month after injection. 2-Disability
      of arm, shoulder and hand (DASH) questionnaire was done before injection, one, two and three
      months after injection.

      Statistical analysis:

      The collected data were analyzed using Statistical Package of Social Science (SPSS) program
      for windows (version 16) and Medcalc program. Quantitative parametric data were presented in
      means and standard deviations (SD) while non-parametric data were presented in median and
      range. On testing significance of parametric quantitative data, t-test and ANOVA test were
      used where the later followed by post hoc test. On testing significance of non-parametric
      data, Mann-Whitny test, Wilcoxon rank test and Kruskal-Wallis test were used where the later
      followed by post hoc test. Statistically significant results were considered if p value <
      0.05. If p values < 0.001, results were considered highly statistically significant.
    

Intervention name(s): Platelet rich plasma; ketamine and bupivacaine injection
Intervention type(s): Combination Product; Drug
Intervention description(s): combined platelet rich plasma and 1 ml ketamine in a dose of o.5 ml/kg plus 5ml bupivacaine 0.5% in a total volume 10 ml; 1 ml ketamine in a dose of o.5 ml/kg plus 5ml bupivacaine 0.5% in a total volume 10 ml
Other intervention name(s): PRP
Intervention MeSH terms: Ketamine; Bupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Ketamine; pain; platelet rich plasma; mastectomy; shoulder