Anesthesia for patient with rheumatoid arthritis

*notes taken from local master student program

Background:

· Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown cause that primarily affects the peripheral joints in a symmetric pattern.

· Constitutional symptoms, including fatigue, malaise, and morning stiffness, are common.

· Extra-articular involvement of organs such as the skin, heart, lungs, and eyes can be significant.

· RA causes joint destruction and thus often leads to considerable morbidity and mortality.

· The treatment of RA is rapidly advancing with the recent addition of new and innovative therapies.

Pathophysiology:

· RA has an unknown cause.

· Although an infectious etiology has been speculated (eg, Mycoplasma organisms, Epstein-Barr virus, parvovirus, rubella), no organism has been proven responsible.

· RA is associated with a number of autoimmune responses, but whether autoimmunity is a secondary or primary event is still unknown.

· RA has a significant genetic component, and the so-called shared epitope of the HLA-DR4/DR1 cluster is present in up to 90% of patients with RA, although it is also present in more than 40% of controls.

· Synovial cell hyperplasia and endothelial cell activation are early events in the pathologic process that progresses to uncontrolled inflammation and consequent cartilage and bone destruction.

· Genetic factors and immune system abnormalities contribute to disease propagation.

· Major cellular roles are played by CD4 T cells, mononuclear phagocytes, fibroblasts, osteoclasts, and neutrophils, while B lymphocytes produce autoantibodies (ie, rheumatoid factors [RFs]).

· Abnormal production of numerous cytokines, chemokines, and other inflammatory mediators (eg, tumor necrosis factor alpha [TNF-alpha, interleukin (IL)–1, IL-6, transforming growth factor beta, IL-8, fibroblast growth factor, platelet-derived growth factor) have been demonstrated in patients with RA.

· Ultimately, inflammation and exuberant proliferation of synovium (ie, pannus) leads to destruction of various tissues such as cartilage, bone, tendons, ligaments, and blood vessels.

· Although the articular structures are the primary sites, other tissues are also affected.

Mortality/Morbidity:

· RA does not usually follow a benign course.

· It is associated with significant morbidity, disability, and mortality.

· Daily living activities are impaired in most patients.

· Spontaneous clinical remission is uncommon (approximately 5-10%).

· After 5 years of disease, approximately 33% of patients will not be working; after 10 years, approximately half will have substantial functional disability.

· Poor prognostic factors include persistent synovitis, early erosive disease, extra-articular findings (including subcutaneous rheumatoid nodules), positive serum RF findings, family history of RA, male sex, and advanced age.

· Life expectancy for patients with RA is shortened by 5-10 years, although those who respond to therapy may have lower mortality rates.

· Increased mortality rates are associated with poor functional status, age, male sex, socioeconomic factors (eg, level of education), positive RF findings, extra-articular disease, elevated acute phase response (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and increased clinical severity (eg, more involved joints).

· Mortality is increased by causes such as infections, cardiovascular disease, renal disease, GI bleeding, and lymphoproliferative disorders; these events may be directly due to the disease and its complications (eg, vasculitis, amyloidosis) or to therapy-induced adverse effects.

Sex:

· Females are 2-3 times more likely to develop RA than males.

Age:

· The frequency of RA increases with age and peaks in persons aged 35-50 years.

· Nevertheless, the disease is observed in both elderly persons and children.

· Juvenile inflammatory arthritis (JIA) has been classified as polyarticular (multiple joints), pauciarticular (<5 joints), and systemic.

· Systemic JIA is often associated with fever, rash, and organ involvement; it is also called Still disease.

· Children with polyarticular RF-positive arthritis generally have a clinical course similar to those with adult RA.

History:

· developed the following criteria for the classification of RA.

1. Morning stiffness: This occurs in and around the joints and lasts at least 1 hour before maximal improvement.

2. Arthritis of 3 or more joint areas: At least 3 joint areas simultaneously have soft tissue swelling or fluid (not bony overgrowth). The 14 possible areas are right or left proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrist, elbow, knee, ankle, and metatarsophalangeal (MTP) joints.

3. Arthritis of hand joints of at least one area swollen in a wrist, MCP, or PIP joint

4. Symmetric arthritis with simultaneous involvement of the same joint areas on both sides of the body: Bilateral involvement of PIPs, MCPs, and MTPs is acceptable without absolute symmetry.

5. Rheumatoid nodules: Subcutaneous nodules are present over bony prominences or extensor surfaces or in juxta-articular regions.

6. Serum RF: Abnormal amounts of serum RF are demonstrated by any method for which the result has been positive in fewer than 5% of healthy control subjects.

7. Radiographic changes typical of RA on posteroanterior hand and wrist radiographs, which must include erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints: Osteoarthritic changes alone do not qualify.

· A patient can be classified as having RA if 4 of 7 criteria are present.

· Criteria 1-4 must be present for at least 6 weeks, and a physician must observe criteria 2-5.

· Patients often present with constitutional complaints including malaise, fever, fatigue, weight loss, and myalgias.

· They may report difficulty performing activities of daily living (eg, dressing, standing, walking, personal hygiene, using their hands).

· Most patients with the disease have an insidious onset. It may begin with systemic features, such as fever, malaise, arthralgias, and weakness, before the appearance of overt joint inflammation and swelling.

· A small percentage of patients (approximately 10%) have an abrupt onset with the acute development of synovitis and extra-articular manifestations. Spontaneous remission is uncommon, especially after the first 3-6 months.

Physical:

· Joint involvement is the characteristic feature of patients with RA.

· In general, the small joints of the hands and feet are affected in a relatively symmetric distribution.

· Those most commonly affected joints, in decreasing frequency, are the MCP, wrist, PIP, knee, MTP, shoulder, ankle, cervical spine, hip, elbow, and temporomandibular.

· Joints show inflammation with swelling, tenderness, warmth, and decreased range of motion.

· Atrophy of the interosseous muscles of the hands is a typical early finding. Joint and tendon destruction may lead to deformities such as ulnar deviation, bouton and swan-neck deformities, hammer toes, and occasionally joint ankylosis.

· Other commonly observed musculoskeletal manifestations are tenosynovitis and associated tendon rupture (due to tendon and ligament involvement, most commonly involving the fourth and fifth digital extensor tendons at the wrist), periarticular osteoporosis due to localized inflammation and generalized osteoporosis due to systemic chronic inflammation, immobilization-related changes or corticosteroid therapy, and carpal tunnel syndrome.

· Most patients have muscle atrophy from disuse, which is often secondary to joint inflammation.

Effect of RA on organs and organ systems

· Skin: Subcutaneous nodules (rheumatoid nodules) occur in many patients with RA whose RF value is abnormal. They are often present over pressure points (eg, olecranon). Vasculitic lesions of the skin may manifest as palpable purpura or skin ulceration.

· Cardiac: Asymptomatic pericardial effusions are common; symptomatic pericarditis and constrictive pericarditis are rare. Myocarditis, coronary vasculitis, valvular disease, and conduction defects are occasionally observed.

· Pulmonary: RA involvement of the lungs may take several forms, including pleural effusions, interstitial fibrosis, nodules (Caplan syndrome), and bronchiolitis obliterans-organizing pneumonia.

· GI: Intestinal involvement, as with kidney involvement, is often secondary to associated processes such as medication effects, inflammation, and other diseases. The liver is often affected in patients with Felty syndrome (ie, RA, splenomegaly, and neutropenia).

· Renal: The kidneys are not commonly directly affected by RA. Secondary involvement is common, including that due to medications (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], gold, cyclosporin), inflammation (eg, amyloidosis), and associated diseases (eg, Sjögren syndrome with renal tubular abnormalities).

· Vascular: Vasculitic lesions can occur in any organ but are most commonly found in the skin. Lesions may present as palpable purpura, skin ulcers, or digital infarcts.

· Hematologic: Most active patients have an anemia of chronic disease. Several hematologic parameters parallel disease activity, including normochromic-normocytic anemia, thrombocytosis, and eosinophilia, although the latter is uncommon. Leukopenia is a finding in patients with Felty syndrome.

· Neurologic: Entrapment of nerves is common, such as with the median nerve in carpal tunnel syndrome. Vasculitic lesions, mononeuritis multiplex, and cervical myelopathy may cause serious neurological consequences.

· Ocular: Keratoconjunctivitis sicca is common in RA and is often the initial manifestation of secondary Sjögren syndrome. The eye may also have episcleritis, uveitis, and nodular scleritis that may lead to scleromalacia.

· The american college of rheumatology developed criteria to aid in determining the progression, remission, and functional status of patients with RA.

· Progression of RA (clinical and radiological staging)

o Stage 1 (early RA)

§ No destructive changes observed upon roentgenographic examination

§ Radiographic evidence of osteoporosis possible

o Stage II (moderate progression)

§ Radiographic evidence of periarticular osteoporosis with or without slight subchondral bone destruction

§ Slight cartilage destruction possible

§ Joint mobility possibly limited; no joint deformities observed

§ Adjacent muscle atrophy

§ Extra-articular soft tissue lesions (eg, nodules, tenosynovitis) possible

o Stage III (severe progression)

§ Radiographic evidence of cartilage and bone destruction in addition to periarticular osteoporosis

§ Joint deformity (eg, subluxation, ulnar deviation, hyperextension) without fibrous or bony ankylosis

§ Extensive muscle atrophy

§ Extra-articular soft tissue lesions (eg, nodules, tenosynovitis) possible

o Stage IV (terminal progression)

§ Fibrous or bony ankylosis

§ Criteria of stage III

· Remission of RA - Five or more of the following conditions present for at least 2 consecutive months

o Duration of morning stiffness not exceeding 15 minutes

o No fatigue

o No joint pain

o No joint tenderness or pain with motion

o No soft tissue swelling in joints or tendon sheaths

o ESR of less than 30 mm/h for a female or less than 20 mm/h for a male

· Functional status of patients with RA

o Class I - Completely able to perform usual activities of daily living

o Class II - Able to perform usual self-care and vocational activities but limited in avocational activities

o Class III - Able to perform usual self-care activities but limited in vocational and avocational activities

o Class IV - Limited in ability to perform usual self-care, vocational, and avocational activities

Causes:

· The cause(s) of RA is unknown.

· Genetic, environmental, hormonal, immunologic, and infectious factors may play significant roles. Socioeconomic, psychological, and lifestyle factors may influence disease outcome.

Investigation

· No pathognomonic test is available to help confirm the diagnosis of RA; instead, the diagnosis is made using clinical, laboratory, and imaging features.

· Markers of inflammation, such as ESR and CRP, are associated with disease activity; additionally, the CRP value over time correlates with radiographic progression.

· Hematologic parameters include a CBC count and synovial fluid analysis.

· Complete blood cell count

§ Anemia of chronic disease is common and correlates with disease activity; it improves with successful therapy.

§ Hypochromic anemia suggests blood loss, commonly from the GI tract (associated with NSAIDs).

§ Anemia may also be related to disease-modifying antirheumatic drug (DMARD) therapy.

§ Thrombocytosis is common and is also associated with disease activity.

§ Thrombocytopenia may be a rare adverse event of therapy and may occur in patients with Felty syndrome.

§ Leukocytosis may occur but is usually mild.

§ Leukopenia may be a consequence of therapy or a component of Felty syndrome, which may then respond to DMARD therapy.

· Synovial fluid analysis

§ An inflammatory synovial fluid (WBC count >2000/mL) is present with counts generally from 5,000-50,000/mL.

§ Usually, neutrophil predominance (60-80%) is observed in the synovial fluid (in contrast with mononuclear cell predominance in the synovium).

§ Note that because of a transport defect, the glucose levels of pleural, pericardial, and synovial fluids from patients with RA are often low compared to serum glucose levels.

· Immunologic parameters include RF, antinuclear antibodies, and, possibly, other newer antibodies (anti-RA33, anti-CCP).

· Rheumatoid factor

§ RF is present in approximately 60-80% of patients with RA over the course of their disease but is present in fewer than 40% of patients with early RA.

§ RF values fluctuate somewhat with disease activity, although high-titered RF generally remains present even in patients with drug-induced remissions.

· Antinuclear antibodies:

· These are present in approximately 40% of patients with RA, but test results for antibodies to most nuclear antibody subsets are negative.

· Newer antibodies (eg, anti-RA33, anti-CCP)

§ These need further validation before their general use can be recommended.

§ Recent studies of anti-CCP antibodies suggest a sensitivity and specificity similar to RF but an increased frequency of positive results in early RA.

Radiology

· Radiographs: Note that erosions may be present in the feet, even in the absence of pain and in the absence of erosions in the hands.

o Extremities - Hands, wrists, knees, feet, elbows, shoulders, hips, cervical spine

o Others when indicated

· MRI: assessment of cervical spine; early recognition of erosions

· Sonography: This allows recognition of effusions in joints that are not easily accessible (eg, hip joints, shoulder joints in obese patients) and cysts (Baker cysts).

· Bone scanning: Findings may help to distinguish inflammatory from noninflammatory changes in patients with minimal swelling.

· Densitometry: Findings are useful for helping diagnose changes in bone mineral density indicative of osteoporosis.

Medical Care:

· Optimal care of patients with RA requires an integrated approach of pharmacologic and nonpharmacologic therapies.

Nonpharmacologic

· Education is important in helping patients to understand their disease and to learn how to cope with its consequences.

· Physiotherapy and physical therapy are initiated to help improve and sustain range of motion, increase muscle strength, and reduce pain.

· Occupational therapy is initiated (1) to help patients to use joints and tendons efficiently without stressing these structures, (2) to help patients decrease tension on the joints through the use of specially designed splints, and (3) to help patients to cope with daily life through the use of adaptations to the patients' environment and the use of different aids.

· Orthopedic measures include reconstructive and replacement-type surgical measures.

Pharmacologic

· The most important measure to successfully treat RA is the use of DMARDs.

· DMARDs can retard or prevent disease progression and, thus, joint destruction and subsequent loss of function.

· DMARDs can be classified into xenobiotic and biologic agents.

Xenobiotic agents

· The xenobiotic DMARDs, ie, gold salts (eg, aurothiomalate, auranofin, others), D-penicillamine, chloroquine and hydroxychloroquine, sulfasalazine (SSZ), methotrexate (MTX), azathioprine, and cyclosporin A.

· MTX and SSZ are the most active compounds in terms of frequency of remissions and time to onset of action and provide the best risk-benefit ratios.

· MTX alone or in combination with other agents has become the standard of care for moderate-to-severe RA.

· Monitoring of CBC counts and liver enzymes is important because of the drugs' hematologic and hepatic toxicities.

· Approximately 1% of patients develop agranulocytosis to SSZ or pneumonitis to MTX.

· Leflunomide is usually initiated with a loading dose of 100 mg/d for 3 days and is then continued at 20 mg/d.

· CBC counts and liver enzymes also must be monitored.

· Most of these drugs have been shown to improve signs and symptoms (as well as quality of life) and to significantly retard radiographic progression of RA.

· Combination therapy appears to be helpful in patients whose RA insufficiently or completely fails to respond to monotherapy with a DMARD.

· Several compounds have been successfully combined without unexpected added risks; these usually include MTX as one of the drugs, ie, MTX plus cyclosporine A, MTX plus SSZ plus an antimalarial, MTX plus leflunomide, or MTX plus biologics.

· The most important and most common adverse events relate to liver and bone marrow toxicity (MTX, SSZ, leflunomide, azathioprine, gold compounds, D-penicillamine), renal toxicity (cyclosporine A, parenteral gold salts, D-penicillamine), pneumonitis (MTX), allergic skin reactions (gold compounds, SSZ), autoimmunity (D-penicillamine, SSZ, minocycline) and infections (azathioprine, cyclosporine A).

· Antimalarials may cause ocular toxicity.

· Adverse events typically become more rare after the first 2-3 months.

· Most adverse events are reversible with cessation of the drugs or with reduction of the doses.

Biologic agents

· The recognition of TNF-alpha and IL-1 as central proinflammatory cytokines has led to the development of agents that block these cytokines or their effects.

· The first such biologics were the TNF blockers etanercept and infliximab. Etanercept, a bivalent p75–TNF receptor linked to the Fc portion of human IgG, is administered at 25 mg SC twice weekly, with or without concomitant MTX.

· Infliximab, a chimeric monoclonal antibody against TNF-alpha, is administered at doses of 3 mg/kg IV at weeks 0, 2, and 6 and then every 4-8 weeks, usually with MTX.

· These agents bind TNF and thus prevent its interaction with its receptors; infliximab binds to cells that express membrane TNF, while etanercept binds lymphotoxin (formerly termed TNF-beta) in addition to soluble TNF-alpha.

· Failure to respond to one TNF blocker does not preclude response to another.

· As with xenobiotics, the decision to continue or stop biologic agents can often be made within 3 months after initiation of therapy.

· Adverse effects associated with the biologic agents include the generation of antibodies against these compounds, emergence of antinuclear antibodies, occasional drug-induced lupuslike syndromes, and infections (including tuberculosis).

· Rarely, demyelinating disorders and bone marrow suppression may occur.

·  Acute and chronic infections, demyelinating disorders, and recent malignancies are contraindications for TNF blockers.

Glucocorticoids

· Glucocorticoids are potent anti-inflammatory drugs and are commonly used in patients with RA to bridge the time until DMARDs are effective.

· Doses of up to 10 mg of prednisone per day are typically used, but some patients may require higher doses.

· Timely dose reductions and cessation are important because of the adverse effects associated with long-term steroid use.

Nonsteroidal anti-inflammatory drugs

· NSAIDs interfere with prostaglandin synthesis through inhibition of the enzyme cyclooxygenase (COX), thus reducing swelling and pain.

· However, they do not retard joint destruction and, therefore, when used alone, are not sufficient to treat RA.

· Similar to glucocorticoids, they can be reduced in dose or discontinued with successful DMARD therapy.

· Several dozen NSAIDs are available and can be classified into different groups of compounds.

· Commonly used NSAIDs include ibuprofen, naproxen, ketoprofen, piroxicam, and diclofenac.

· In the early 1990s, 2 isoforms of COX were discovered, ie, COX-1 and COX-2.

· Traditional NSAIDs inhibit both COX-1 and COX-2.

· The coxibs (COX-2 inhibitors), a new group of compounds, have recently been developed.

· These compounds have a significant preference for COX-2 over COX-1. COX-1 has a protective role, particularly in the stomach, while COX-2 is strongly up-regulated during inflammation.

· Coxibs, with their selectivity for COX-2, have been shown to be clinically efficacious and are accompanied by significantly reduced GI toxicity, the major adverse event related to the use of nonselective COX inhibitors (ie, NSAIDs).

· Other adverse effects, such as water retention, hypertension, and abnormal transaminase levels, are observed with both nonselective and COX-2–selective drugs.

Analgesics

· Acetaminophen/paracetamol, tramadol, codeine, opiates, and a variety of other analgesic medications can also be employed to reduce pain.

· These agents do not affect swelling or joint destruction.

Anesthesia for rheumatoid arthritis

Preanesthetic assessment

History

· Thorough history to assess the nature and severity of rheumatoid disease, extraarticular manifestations

· Medications history to find nature and possible side effect;

· NSAIDS;aspirin interfere with platelets function and renal function

· Corticosteroids, gold, methotrexate give rise to adrenal insufficientcy, pulmonary impairment , immunosuppression

Examination

· Through systematic examination to assess the extent of systemic involvement

· Airway assessment

· Examine for mouth opening .

Investigation

· Routine investigation

· Neck xr ; to detect the presence of cervicall spine abnormalities

· Assume all rheumatoid arthritis undergoing emergency sx having cervicall spine disease

Anesthetic consideration

choice of anesthesia

· regional anesthesia preffered over general anesthesia because airway problem

· If general anesthesia chosen , awake fibreoptic intubation preffered over larnygoscopy

· if intubation is needed , airway adjunct is preffered over ett intubation

· Avoid intubation if possible

Regional anesthesia concern;

· Difficulty for optimal position of the back

· Difficulty to locate intrathecal/epidural space

· Maybe unwise to give regional anesthesia in cases of anticipated intubation difficulty

· Reason ; suboptimal intubation condition if failed spinal, high block or total spinal

Airway concerns

· Instability of cervicall spine and excessive movement during intubation, cervical cord damage

· Need to anticipate difficulty for airway instrumentation, and maybe impossible for laryngoscopy and visualize vocal cords due to limited neck movement with cervicall spine abnormalities

· Perform gentle intubation with ett one size smaller to reduce the risk of larygeal edema and cricoarthnoid joint dislocation

· monitor and ascertain the presence of stridor and airway obstruction extubation

· Choice of airway; maybbe pruudent to consider awake fibreoptic intubation, avoid ett intubation