Intra-articular & Allied Injections Sureshwar Pandey, Anil Kumar Pandey
INDEX
Page numbers followed by f refer to figure.
A
Abductor pollicis longus 37
Acetonide, triamcinolone 71
Achilles tendinitis 55
Acupressure 8587
Acupuncture, complications of 86
Adventitious superficial pretendinous achilles bursa 55
Allergic rhinitis, recurrent 71
Alopecia 14
Analgesic 8, 79
Ankylosing spondylitis, peripheral synovial swelling of 12
Ankylosis, fibrous 12, 71
Anorexia 92f
Anserinus bursa 49
Apophysitis 12
calcaneal 12, 55, 56f
Arthritis 86
crystal 51
degenerative 51
gouty 51, 58
infective 78
rheumatoid 12, 17, 51, 58, 70
traumatic 16, 51
Arthropathy 79
Arthrosis, degenerative 71
Asthma 93f
Atrophy 79
B
Backache 14
Bacteraemia 78
Bell's palsy 75
Bhadrasan 91
Bhujangasan 93f
Blood transfusion 80
Botulinum toxin 82, 83
role of 82
Budha's position 45
Bupivicaine 8
C
Calcaneal spur syndrome 55
Cerebellar artery
anterior inferior 77
superior 77
Cerebellopontine angle 77
Chloroquine 8
Chymopapain 60
Coccydodynia 67, 68f
Coccyx, painful 67
Colles fracture 36
Computer controlled local anaesthetic delivery system 25
Corticosteroid 3, 19, 80
cocktail injection 77
infiltration 14
injection 11, 12, 13, 70
intra-articular 7
ophthalmic indications of 75
therapy 16, 79
Crohn's disease 87
Cytostatica 8
D
De-Quervain's disease 12, 37, 38, 38f, 86, 87
Dermatitis 14
Dextrose 8
Diatrizoate meglumine 61
Discography 61
Disseminated lupus erythematosus 14
Dyspepsia 92f
E
Elbow 32
Electrolyte balance 80
Epicondylitis
lateral 10, 12, 33
medial 12, 35
Epidermoid 77
Epidural injections, complications of 65
Extensor
pollicis brevis tendon 37
tendon, ganglion of 39f
Extracorporeal shock-wave therapy 34
F
Fibro-fatty nodules 14, 68, 68f
Fibrositis, recurrent 69
Fractures, intra-articular 12, 16
Freiberg's infarction 15
G
Ganglion 37
intra-articular 39f
Gastrointestinal system 94f
Glucocorticoids 2
Glucosamine 8
Glucosaminoglycan 17
Golfer's elbow 10, 12, 35
H
Haemarthrosis 12
Haemostatic disorder 16
Haglund deformity 55
Hallux rigidus 15
Hallux valgus 15
Hansen's disease 66
Hansen's neuritis 14, 26
Hansen's neuropathy 66
Hansen's pathology 75
Hathyoga 91
Heel syndrome, painful 53, 55f
Hexacetonide, triamcinolone 80
Hyaluronan solution 17
Hyaluronate 17
Hyaluronic acid 19
intra-articular 17
role of 17, 19
Hyaluronidase 7
Hydrocortisone acetate 6
I
Indoprofen 8
Infection
management of 79
sites of 61f
International Yoga Day 90
Intra-articular injections, complications of 78
Iothalamate meglumine 61
Ischiogluteal bursitis 15
J
Jaw, postoperative ankylosis of 72
Joints
acromioclavicular 73, 74f
ankle 51, 52f
around clavicle 73
degenerative arthrosis of 12
disruption, severe 16
elbow 32, 33f, 34f
facet 65
hip 42, 43f
interphalangeal 40, 40f, 58
knee 23f, 45, 46f48f, 49
metacarpophalangeal 40
metatarsophalangeal 58
neuropathic 16
post-immobilization stiffness of 12
post-traumatic stiffness of 12
recurrent subluxation of 72
sacroiliac 59, 69f, 70
shoulder 27, 28f30f
sprained ligaments of 13
sternoclavicular 73, 74f
strained ligaments of 13
subtalar 54f, 58
surface, aseptic necrosis of 26
unstable 16
wrist 36, 37f
K
Karma yoga 91
Keloid 14
Kidney function 80
Knee 9
primary osteoarthritis of 12
Kyphoplasty 66
L
Lactic acid 8
Leucoderma 14
Ligaments
nonspecific inflammation of 14
post-traumatic adhesions of 13
Little league elbow syndrome 35
Lumbar disc disease 60, 61f
Lung diseases 93f
M
Makarasan 93f
Meningioma 77
Meralgia paresthetica 14, 43, 43f
Methylprednisolone acetate 81
Metrizamide 61
Mickel's cave 77
Morphine 8
Morrant-Baker cyst 48
Morton's toe 15
Mucopolysaccharide polysulfuric acid ester 8
N
Nerve
peripheral 14, 59, 66
root injection, method of 66
trigeminal 76f
Neuralgia, trigeminal 75, 76, 76f, 77
Neuritis
adhesive 14
herpetic 60, 61f
peripheral 14
Neuroma
acoustic 77
painful 14
Nodule, fibrotic 13
O
Old pelvic fracture 69
Olecranon bursitis 34, 34f
Osgood-Schlatter disease 12, 49, 50f
Osteoarthritis 19
management of 17
Osteoporosis, severe 16
P
Padmasan 91, 92f
Pellegrini-Stieda disease 13
Periarthritic infiltration 28, 29f
Periarthritis shoulder 12
Perinural adhesions, post-traumatic 14
Peroneus longus tendon 53, 54f
Phenylbutazone 8
Pitcher's elbow 35
Plantar fasciitis 14, 55, 56, 57f
Platelet-rich plasma 17, 20
Polymethylmethacrylate 66
Popliteal nerve 67
lateral 49, 50f
Post-achilles bursitis 55, 56f
Pre-achilles bursitis 55, 55f
Psoriatic arthropathy 12
Pyaemia 78
R
Radiculitis 14
Reflex sympathetic dystrophy syndrome 15
Reiter's syndrome 12
Retromastoid cranioctomy 77
Rhinitis, atrophic 71
S
Sacral hiatus 63, 63f
Sarpasan 91
Sciatic nerve 69, 69f
Sclerosis, multiple 77
Septicaemia 78
Shock 80
Shoulder syndromes, painful 87
Sidhasan 91
Sodium pentosan polysulfate 8
Somatostatin 8
Sphenopalantine neuralgia 77
Spine 59
Spondylitis
ankylosing 70, 93f
rheumatoid 70
Spondylosis
cervical 93f
lumbar 93f
Sports injuries, acute 21
Staphylococcus aureus 78
Stenosing tenosynovitis 37
Steroid 79
Sukhasan 91
Suprapatellar pouch 47f
Surya namaskar 94f
Synovitis 72
traumatic 51
T
Tailor's bunion 15
Temporomandibular joint 72f
Tendon 13
injuries, chronic 21
ruptures 79
Tennis elbow 33
extra-articular 12, 33
Tenosynovitis, bicipital 31
Tenoxicam 8
Thoracic region 62
Tibial tuberosity, apophysitis of 49
Tibialis posterior
tendon 53f
tendo-vaginitis of 58
Trigeminal ganglion balloon compression 77
U
Ulnar nerve 67
V
Vajrasan 92f
Vascular compression 77
Vertebroplasty 66
Vitamin
B complex 79
C 79
X
Xiphisternum 73
Y
Yoga 90
Z
Zygapophyseal joint 65
×
Chapter Notes

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Principles of Intra-articular and Allied InjectionsCHAPTER 1

Chapter Outline
  • ◆ Mode of action of glucocorticoids
  • ◆ Immune responses
  • ◆ Anti-inflammatory properties
  • ◆ Potency
“Change is inevitable, progress is a choice.”
—Dean Lindsay
 
INTRODUCTION
It is more than five decades from now that Philip Hench and his colleagues introduced the corticosteroids with a lot of fan and fair (triumphal and trumpeted introduction indeed) for managing rheumatoid arthritis at the Mayo clinic in 1949.
In fact, Kendall and Hench in America and Reichstein in Switzerland jointly won the Nobel Prize for the introduction of cortisone, which was used for the first time in 1948 for treating rheumatoid arthritis. Soon after it was observed by Philip Hench and his colleagues at Mayo clinic (1949) that hydrocortisone was active at tissue level in reducing the inflammatory changes. However, now responsible physicians always want to ward off the steroids or wean them off (if it has already being used) as far as possible. Of course, its one use still remains and perhaps will remain (till some harmless substitute come in the medical arena) universally employed and that is its intra-articular, periarticular and intra-lesional injections/infiltrations.
The joint aspiration was practiced as early as in 1930s. Perhaps the first intra-articular injections were of formalin and glycerin, lipidol, lactic acid and petroleum jelly which yielded some benefit (Pemberton R 1935; Ropes MW and Bauer W 1953).
Joe Hollander (1951) was the first to introduce the local infiltrative use and intra-articular injection of hydrocortisone acetate to control pain and limit the inflammatory process, whether induced by trauma, collagen arthropathy or crystallopathy or similar conditions. He observed much better clinical response in a series of more than 100,000 hydrocortisone acetate injection in 4,000 patients. Oral use of corticosteroids is very popular with the physicians even general practitioners, but its local use demands a skilled approach, a knowledge placement and careful precautions to avoid infections. The surgeons2 or rheumatologists or gynecologists or dermatologists or ophthalmologists need to know absolutely where, when, how, why and why not to use it.
Hollander was perhaps one of the first to use compound F (hydrocortisone acetate) into an inflamed joint due to rheumatoid arthritis and had also used prednisolone tertiary butyl acetate to prolong the benefit. Hydrocortisone acetate (an acetate ester of hydrocortisone) is a very fine white odorless crystalline powder and is practically insoluble in water (considerably less soluble than the hydrocortisone in aqueous media). It melts at a temperature of 216–220°C. One gram dissolves in 230 mL of alcohol and 150 mL of chloroform.
The preparation most commonly, effectively and widely used till recently is hydrocortisone tertiary acetate ester of triamcinolone acetinide (TATBA). The chemical formula of hydrocortisone acetate is C23H32O6. The injection available is a sterile suspension of hydrocortisone acetate in sodium chloride solution, containing a dispersing agent.
The usual dose of hydrocortisone acetate for intra-articular injection is 25 mg for an average joint with a variation from 0.5 to 50 mg. Several joints can be injected simultaneously.
 
MODE OF ACTION OF GLUCOCORTICOIDS
Glucocorticoids diffuse across the cell membrane and form a complex with specific cytoplasmic receptors. These complexes enter the nucleus of the cell, bind to the DNA and stimulate transcription of mRNA and later protein synthesis of various enzymes. On the whole, this is the basic biochemical action of the steroid which accounts for the various and numerous effects after the systemic use.
As such the mode of action of adrenocortical steroids has been mainly discussed around:
  1. Immune responses.
  2. Anti-inflammatory properties.
However, they also influence the carbohydrate, protein and fat metabolism. They also affect the working of cardiovascular system, skeletal system, skeletal muscles and the central nervous system.
 
IMMUNE RESPONSES
The mode of immune responses, as yet, has not been clearly defined. They are believed to modify the clinical course of different diseases in which hypersensitivity is believed to play an important role. They do not interfere with the normal mechanism of development of cell-mediated immunity. Probably, they prevent or suppress the inflammatory responses that take place as a consequence of hypersensitivity reactions.
 
ANTI-INFLAMMATORY PROPERTIES
Researches are still on to understand clearly the anti-inflammatory properties of corticosteroids. However, for the clinicians it is perhaps enough to understand that corticosteroids inhibit the inflammatory responses, whether the inciting agent is radiant, mechanical, chemical, infectious or immunological. It must be borne in mind that there is only suppression of the inflammatory effect, while the underlying causes of the diseases remain unaffected. It is this property of3 corticosteroids that provides them almost unique potential for therapeutic disaster. Hence, the epitomized remark, at times, stands true that corticosteroids, if misused, permit a patient to walk slowly all the way to the autopsy room. However, the recent works in more detail have projected variable positive thinking about the role of intra-articular corticosteroids.
Corticosteroids exert their anti-inflammatory action by interrupting the inflammatory and immune cascade at several levels including: impairment of antigen opsonization, interference with inflammatory cell adhesion and migration through vascular endothelium, interruption of cell-cell communication by alteration of release or antagonism of cytokines (interleukin –1), impairment of leukotriene and prostaglandin synthesis, inhibition of production of neutrophil superoxide, metalloprotease and metalloprotease activator (plasminogen activator) and decreased immunoglobulin synthesis (Gaffney et al. 1995).
Intra-articular steroids, probably, reduce the number of lymphocytes, macrophages and mast cells, which in turn reduces phagocytosis, lysosomal enzyme release and the release of inflammatory mediators (Snibbe and gambardella 2005). Thus inflammation is reduced, especially due to reductions in the release of interleukin-1, leukotrienes and prostaglandins (Uthman et al. 2003) and the pain is relieved.
Against earlier reported that corticosteroids injections may suppress cartilage proteoglycan synthesis, worsen cartilage lesion or even cause degenerative lesion in normal cartilage (Raynauld 1999), recent reports have shown that low dose intra-articular corticosteroids (sufficient to suppress catabolism) normalized proteoglycan synthesis and significantly reduced the incidence and severity of cartilage erosions and osteophyte formation (Raynauld JP et al. 2003). In humans, repeated corticosteroid injection in knees of patients with chronic arthritis presented no evidence of destruction or accelerated deterioration (Friedman and Moore, 1980).
The local or intra-articular injection of the corticosteroids does not appear to have significant systemic effects. However, it does not mean that it is all full proof. Slowly there may be a gross damage of the articular cartilage following injudicious repeated use of intra-articular corticosteroids.
The local mode of action is again not clearly defined. Though pioneers have devoted their time and mind to illustrate the exact mode of action of intra-articular hydrocortisone acetate and allied substance (Table 1 on page 94) the controversy still exists. Kantrowitz et al. (1975) suggested that the anti-inflammatory property of corticosteroid emanate from their capacity to inhibit production of prostaglandin (a potent mediator of inflammatory response) in the synovium.
Clinical effects of suppression of nonspecific inflammation and reduction of swelling and pain to varying extent have been noticed in most of the cases with intra-articular injection of the corticosteroids. However, in certain cases it appears as only a palliative therapy and at another few occasions it proves to be ineffective.
It has been noticed that at times even a placebo injection into the joint or even just pricking into the joint helps in relieving the chronic pain to varying extent. This may be explained, more or less on the comparable lines of using electrical stimulation and acupuncture to relieve the chronic pain. Probably, they act by closing a hypothetical GATE in the spinal cord, thereby blocking pain stimuli from reaching the brain. Puncturing stimulates small nerve fibers sending4 impulses through the OPEN GATE that registers in brain as acute pain. When the signals reach the central biasing mechanism of the brainstem, they trigger counter impulses, which travel down the spinal cord and close the GATE against the chronic pain. However, this is just a hypothesis. Various research works, being done to find the effective ways and means of tackling the problem of pain, point to a new attractive approach basing upon the opposite principles of stimulating the inhibitory systems. Of course, it is too early to provide an objective evaluation of such possibilities. Low doses of intra-articular steroids have been noticed to reduce the size, severity and progression of both, lesions of the cartilage and osteophyte formation (William 1985, Pelletier et al. 1994).
Though Moskowitz et al. (1985) and Behrens (1975) have raised the possibilities of adverse effects of intra-articular corticosteroids on the articular cartilage, varying benefits from such injections cannot be denied (Freidman 1980, Dieppe et al. 1980, Pandey 1982), rather its judicious use can always be beneficial (Pandey 1982).
It has been a general tendency to use intra-articular steroids in late stage of osteoarthritis or other similar arthritic conditions, but this strategy needs to be changed in light of the experimental evidences, which indicate that intra-articular steroids exert a chondroprotective effect—it is probably by the suppression of stromelysin synthesis, a metalloprotease implicated in osteoarthritic cartilage degradation. However, though pain relief by intra-articular corticosteroids can be dramatic, its long-term chondroprotective effects need further authentication.
Hydrocortisone the natural hormone, being too much soluble was found to disperse too quickly, and thus, could not leave its prolonged effects locally. Hence, its chemically improved ester form hydrocortisone acetate (C23H32O6), the primary alcohol group of C23 being the one esterified, was developed and found to be suitable. It is considerably less soluble than hydrocortisone in aqueous media, rather for all practical purposes hydrocortisone acetate may be taken as insoluble in water. It melts at a temperature of 216–220°C. One gram dissolves in 230 mL of alcohol and 150 mL of chloroform. When prepared in microcrystalline form and mixed with other agents it forms a stable suspension, which can be injected locally where it remains deposited for several weeks, gradually releasing the hydrocortisone to produce its anti-inflammatory effects for longer period. The successful attempt to restore the comfort and mobility of rheumatoid affected joints by local injection of hydrocortisone acetate (compound F) into the inflamed joint was by Hollander, the Philadelphia rheumatologist in 1951. He used prednisolone tertiary butyl acetate to prolong the benefit. McCarty, the Hollander's colleague rheumatologist in Philadelphia, showed that the very long-lasting synthetic corticosteroid derivatives, especially triamcinolone hexacetonide (TATBA or THA), could produce remarkable and lasting remissions of the rheumatoid arthritis effects when given as multiple injections at certain intervals, especially in smaller joints (e.g in hands). He equated the result to the ‘medical synovectomy’. With the pioneering work of these two rheumatologists ushered the art and science of local injection therapy for the rheumatic disorders. Of course, the experiences of ameliorating pain by injecting local anesthetic agents into and around the painful spots in the muscles and painful ligaments in the sprains have definite role in establishing the local injection therapy for rheumatoid disorders and allied conditions.
Gradually, there has been great swing in favor of injecting methylprednisolone acetate (chemical name being 6-methyl-delta-1-hydrocortisone) in place of5 hydrocortisone acetate, wherever it is indicated. It is 6-methyl derivative of prednisolone. Methylprednisolone acetate possess the general properties of the glucocorticoid methylprednisolone, but is less soluble, and therefore, less readily metabolized. Thus, after injection into various sites its action is prolonged. It is more or less white odorless crystalline powder which melts at about 215 °C with slight decomposition and is practically insoluble in water. Its molecular formula is “C22H30O5” and has the molecular weight of 374.46.
Like other glucocorticoids, methylprednisolone causes profound and varied metabolic effects. These compounds have also been seen to modify the body's immune response to diverse stimuli.
The rate of systemic absorption of an intra-articular corticosteroid is proportionate to the solubility of the compound. More insoluble compounds are better suited for intra-articular use, since the local duration of action is prolonged and the chances of systemic absorption remain minimum. Methyl-prednisolone acetate and the triamcinolone hexacetonide are widely used for intra-articular injection, followed by the use of triamcinolone acetonide.
 
POTENCY
The potency of 4 mg of methylprednisolone can be obtained from 4.4 mg of methylprednisolone acetate. The anti-inflammatory effect of 20 mg of hydrocortisone is available from the 4.4 mg of methylprednisolone acetate. Mineralocorticoid activity of methylprednisolone is minimal. 200 mg of methylprednisolone is equivalent to 1 mg of desoxycorticosterone. Intra-articular injection of Dysprosium-165-ferric hydroxide macroaggregates has been used for medical synovectomy and has been proved to be an effective treatment for chronic rheumatoid synovitis of the knee with minimum radiographic evidence of lesion of bone and cartilage (stage I or stage II radiographic changes).
The low rates of systemic spread of the isotope offer a definite advantage over previously used agents for radiation synovectomy, e.g. chemical such as osmic acid and alkylating agents, e.g. (thiotepa and nitrogen mustard); several radionuclides in colloidal or particulate form, e.g. yttrium-90, gold-198, ebrium-169, rhenium-186 and phosphorus-32 (Sledge et al. 1987). Dysphrosium-165 is a rare earth element with a half-life of 2.3 hours. It decays mainly by beta emissions. The maximum extent of penetration of the beta emission into the soft tissue is 5.7 mm, which probably approximates the entire synovial lining of the joint.