Rheumatoid arthritis, Prognostic Features, Management and Complications

NICE has stated that clinical diagnosis is more important than criteria such as those defined by the American College of Rheumatology. 2010 American College of Rheumatology criteria Target population. Patients who

• Have at least 1 joint with definite clinical synovitis
• With the synovitis not better explained by another disease

Classification criteria for rheumatoid arthritis (add the score of categories A-D; a score of 6/10 is needed definite rheumatoid arthritis)

Key RF = rheumatoid factor

• ACPA = anti-cyclic citrullinated peptide antibody

Factor                                                                                               Scoring

A. Joint involvement

   1 large joint                                                                                           0

2 - 10 large joints                                                                                     1

1 - 3 small joints (with or without the involvement of large joints)        2

4 - 10 small joints (with or without the involvement of large joints)      3

10 joints (at least 1 small joint)                                                               5

B. Serology (at least 1 test result is needed for classification)

Negative RF and negative ACPA                                                            0

Low-positive RF or low-positive ACPA                                                 2

High-positive RF or high-positive ACPA                                               3

C. Acute-phase reactants (at least 1 test result is needed for classification)

Normal CRP and normal ESR                                                               0

Abnormal CRP or abnormal ESR                                                          1

Rheumatoid arthritis Prognostic Features

A number of features have been shown to predict a poor prognosis in patients with rheumatoid arthritis, as listed below Poor prognostic features

• Rheumatoid factor positive
• Poor functional status at presentation
• Hla dr4
• X-ray: early erosions (e.g. After < 2 years)
• Extra-articular features e.g. Nodules
• Insidious onset
• Anti-ccp antibodies

In terms of gender, there seems to be a split in what the established sources state is associated with a poor prognosis. However, both the American College of Rheumatology and the recent NICE guidelines (which looked at a huge number of prognosis studies) seem to conclude that female gender is associated with a poor prognosis.

Rheumatoid arthritis management

The management of rheumatoid arthritis (RA) has been revolutionized by the introduction of disease-modifying therapies in the past decade. NICE has issued a number of technology appraisals on the newer agents and released general guidelines in 2009. Patients with evidence of joint inflammation should start a combination of disease-modifying drugs (DMARD) as soon as possible. Other important treatment options include analgesia, physiotherapy, and surgery.

Initial therapy

• In the 2009 NICE guidelines, it is recommended that patients with newly diagnosed active RA start a combination of DMARDs (including methotrexate and at least one other DMARD, plus short-term glucocorticoids)

DMARDs

• Methotrexate is the most widely used DMARD. Monitoring of FBC & lfts is essential due to the risk of myelosuppression and liver cirrhosis. Other important side-effects include pneumonitis
• Sulfasalazine
• Leflunomide
• Hydroxychloroquine

TNF-inhibitors

• The current indication for a TNF-inhibitor is an inadequate response to at least two DMARDs including methotrexate
• Etanercept: recombinant human protein, acts as a decoy receptor for TNF-α, subcutaneous administration, can cause demyelination, risks include reactivation of tuberculosis
• Infliximab: monoclonal antibody, binds to TNF-α and prevents it from binding with TNF receptors, intravenous administration, risks include reactivation of tuberculosis
• Adalimumab: monoclonal antibody, subcutaneous administration

Rituximab

• An anti-cd20 monoclonal antibody results in B-cell depletion
• Two 1g intravenous infusions are given two weeks apart
• Infusion reactions are common

Abatacept

• Fusion protein that modulates a key signal required for activation of T lymphocytes
• Leads to decreased T-cell proliferation and cytokine production
• Given as an infusion
• Not currently recommend by NICE

Rheumatoid Arthritis complications

A wide variety of extra-articular complications occur in patients with rheumatoid arthritis (RA):

• Respiratory: pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans, methotrexate pneumonitis, pleurisy
• Ocular: keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration, keratitis, steroid-induced cataracts, chloroquine retinopathy
• Osteoporosis
• Ischaemic heart disease: ra carries a similar risk to type 2 diabetes mellitus
• Increased risk of infections
• Depression

Less common

• Felty's syndrome (RA + splenomegaly + low white cell count)
• Amyloidosis

Paget’s Diseases of Bone

Paget's disease is a disease of increased but uncontrolled bone turnover. It is thought to be primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity. Paget's disease is common (UK prevalence 5%) but symptomatic in only 1 in 20 patients

Predisposing factors

     §  Increasing age

     §  Male sex

     §  Northern latitude

     §  Family history

Clinical features - only 5% of patients are symptomatic

·         Bone pain (e.g. Pelvis, lumbar spine, femur)

·         Classical, untreated features: bowing of tibia, bossing of skull

·         Raised alkaline phosphatase (alp) - calcium* and phosphate are typically normal

·         Skull x-ray: thickened vault, osteoporosis circumscripta

Indications for treatment include bone pain, skull or long bone deformity, fracture, periarticular Paget's

·         Bisphosphonate (either oral risedronate or iv zoledronate)

·         Calcitonin is less commonly used now Complications

·         Deafness (cranial nerve entrapment)

·         Bone sarcoma (1% if affected for > 10 years)

·         Fractures

·         Skull thickening

·         High-output cardiac failure

Usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation Paget's disease - old man, bone pain, raised ALP. The normal calcium and phosphate combined with a raised alkaline phosphate points to a diagnosis of Paget's

Perioperative Management of Surgical Patients

Preoperative preparation is classified into 3 categories according to an urgent degree.

Emergent operation necessary preparations should be done with the shortest time operate immediately.

e.g. rupture of the liver, large vessel in the abdomen.

Date-limited operation:  the date of operation can be selected, but cannot be over prolonged. Preparation is limited with a certain time, so sufficient preparation should be done within this limit.

Elective operation: the date of the operation does not affect the outcome of treatment.

Patients with compromised pulmonary function preoperatively are susceptible to postoperative complications, including hypoxia, atelectasis, and pneumonia.

Risk factors: COPD, smoking, advanced age, obesity, acute respiratory system infection.

Physical examination: wheezing and prolonged expiration.

The most helpful screening pulmonary function tests are forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). Values less than 50% of predicted outcomes based on age and body size indicate significant airway disease with a high risk for complications.

The blood sugar level should be controlled before the operation, water-electrolyte imbalance and acidosis should be corrected, the nutritional state should be improved.

For a suspected infection, antibiotics should be given preoperatively

Before the operation, blood sugar should be at a steady mild elevated state (5.6～11.3 mmol/L) urine sugar + ~ ++.

The operation should be performed as early as possible to avoid long fasting time and ketogenesis

If the operation lasts long, glucose and insulin are given in infusion fluid with a ratio of 5:1.

Dosage of insulin after operation is determined by the urine sugar value within 4-6 h, ++++: 16 U; +++: 12 U; ++: 6 U: +: 0 U. Urine ketone positive: 6U.

Monitoring

• Vital signs
• Central venous pressure
• Other special monitoring items
• Body fluid balance

Incision classification

• Clean Category I ）
• Possibly contaminated Category II）
• Contaminated Category III）

Postoperative fever classified into the infectious & noninfectious origin, with the latter occurring more earlier (1.4 d versus 2.7 d) and temperature lower than the former

Wound infection

• Incident 3-4%, 3-4 days after operation.
• Redness, swelling, hotness, pain & tenderness of incision.
• With or without fever and increment of WBC
• Discharge should be cultured for choosing antibiotics
• Remove suture at the most obvious tender point and open the incision to release pus, etc. 

 

NUTRITION IN THE SURGICAL PATIENTs

Caloric sources

Three major sources: protein, carbohydrate, and fat

Amount of glycogen is limited, only can supply 3765.6 KJ（900 kcal），comprise ½ of daily requirement

Protein cannot be considered as an energy source.

Body fat is the main energy storage about l5Kg. In starvation fat provides the bulk of calories with little effect on organ function, but certain amount of protein also be oxidized

Anthropometry：

Malnutrition: body weight loss > 15%，t

Viscera protein: albumin, etc.

Incapable of oral ingestion > 5-7 days

Preoperative preparation of malnutrition patient, digestive tract fistula, acute severe pancreatitis, short bowel syndrome, severe infection, large area burning, and hepatic, renal failure, etc.

PN after major operation is beneficial to patient's recovery, especially abdominal surgery

Intestinal inflammatory diseases: ulcerative colitis, Crohn disease

Nutrition support may promote tumor proliferation and development, so it should be used in combination with chemotherapy.

Glucose

Main energy source of PN, only 100 g/24 h can save protein

Advantages: sufficient origin, low price, convenient to know its utilization status through monitoring blood & urine glucose 

Disadvantages:

• High concentration: 25% & 50%，irritable to vein 
• Limit of body utilization: 5 mg/(kg·min)
• Surgical patients combined with DM are more susceptible to   
• Glucose metabolism disturbance
• Under stress, body utilization rate decrease, extra glucose turn into fat, dispose in organs

Electrolytes

Potassium, sodium, chloride, calcium, magnesium and phosphorus 

Vitamins

Water soluble: thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, folic acid, B12

Fat soluble: A, D, E, K

Trace metals

Zinc, Copper, Chronium, Selenium, Manganese, Iron

Technical complications: 

• Related to central venous catheter: pneumothorax, injury of blood vessel, nerve or thoracic duct due to puncture.
• Air embolism
• Insufficient replenishment
• Serum electrolyte disturbance
• Trace metal deficit
• Essential fat acid deficit

Hypo/hyperglycemia

•        Hypoglycemia: over-dosage of extraneous insulin
•        Glucose infusion rate too rapid
•        Decreased utilization of glucose

Liver function damage

•        Liver steatosis due to overfeed of glucose
•        Use fat emulsion as part of energy source

Stone formation in the gall bladder: long-term PN without food stimulation to the gut

Mild abnormalities of serum transaminase, alkaline phosphatase and bilirubin levels may occur in many parenterally nourished patients. Intestine barrier function impaired due to lack of food stimulus to the intestine and glutamine insufficiency

Infectious complications

Sepsis secondary to contamination of the central venous catheter

Causes:

Systemic sepsis

• Hematogenous seeding of the catheter with bacteria
• Failure to observe strict aseptic precautions during preparation & administration of the solutions
• Clinical manifestations:
• Sudden development of glucose intolerance
• Fever
• Infectious complications
• Sepsis secondary to contamination of the central venous catheter

Management

• Other causes of fever also should be investigated
• If fever persists, the infusion catheter should be removed and cultured
• Should evidence of infection persists over 24-48 h without a definable source, the catheter should be replaced in the opposite subclavian vein, and antibiotics also should be administrated

Shock Treatment and Management in Surgical Patients

Shock is defined as peripheral circulatory failure causing tissue perfusion to be inadequate to meet the nutritional requirements of the cells and remove the waste products of metabolism

Effective circulating blood volume:

Blood circulating through the cardiovascular system per unit time depends on adequate blood volume, effective cardiac output, and peripheral vascular resistance

Classification of shock

• Hypovolemic
• Septic
• Cardiogenic
• Neurogenic
• Anaphylactic shock
• Shock Monitoring

Consciousness

Reflection of cerebral perfusion & systemic circulation status

Colour and temperature of the skin

Body surface perfusion

Blood pressure

Not the most sensitive sign reflecting shock

Evidence of shock:

• systolic pressure ＜ 90 mmHg,
• systolic & diastolic pressure difference ＜ 20 mmHg

Pulse

• A rapid feeble pulse appears before blood pressure drop
• Shock index = pulse rate/systolic pressure
• 0.5: no shock; 1.0-1.5: evidence of shock;
• ＞2.0: severe shock

Urine output

• Most sensitive index of the adequacy of vital organ perfusion
• ＜ 25 ml/h: possibility of shock
• Normal blood pressure，but oliguria & low specific gravity suggesting renal failure
• ＞ 0.5 ml/kg/h: shock has been corrected

Special Monitoring of Shock

Central venous pressure (CVP)

• Reflecting systemic blood volume & cardiac function
• Normal value: 5-10 cmH₂O
• < 5 cmH₂O: blood volume insufficient
• >15 cmH₂O: heart failure, venous excessive constriction,
•    pulmonary circulation resistance increase
• >20 cmH₂O: congestive heart failure

Treatment and Management of Shock

General Emergent Management

• Keep the patient recumbent, control massive  bleeding, ensure adequacy of the airway          
• Position：head & trunk elevated 20～ 30 degree，lower limbs elevated 15～20 degree，blood return to the heart increase
• Large bore intravenous catheter placed
• Oxygen administered by nasal tube or mask
• Keep patient warm, without heating

Restore blood volume

• Principal means of treating shock
• Crystalloid first
• Colloids: plasma expander, RBC, whole blood

Vigorous treatment of primary diseases

Management principle: after the rapid restoration of effective circulating blood volume, treating primary disease promptly with surgery

Correct acid-base disturbance

Principle: acid rather than basic

Adrenocorticosteroid

Main functions to shock：

• block alpha receptor, dilate vessel ，decrease peripheral resistance，improve microcirculation
• protect intracellular lysosome
• increase myocardial contractility & cardiac output
• improve mitochondria function and prevent aggregation of WBC
• promote gluconeogenesis change lactate into glucose lessen acidosis

Indications: septic or severe shock

The principle of application: high dose (1-3 mg/kg of dexamethasone), intravenous drip infusion use only 1-2 times to prevent the side-effects

All about General anesthesia

Definition

A controllable and reversible loss of consciousness induced by the intoxication of the central nervous system. Lowered sensitivity to external stimuli (hyporeflexia), analgesia, unconsciousness, muscle relaxation, and amnesia are significant features of general anesthesia.

Tree stages of general anesthesia

• Induction of anesthesia
• Maintenance of anesthesia
• Recovery of anesthesia

Inhalational anesthesia

Inhalation anesthetics are substances that are brought into the body via the lungs and are distributed with the blood into the different tissues. The main target of inhalation anesthetics (or so-called volatile anesthetics) is the brain.

MAC

 Definition: MAC is the “minimum alveolar concentration” of an inhaled anesthetic at atmospheric pressure with 100%O2required to prevent movement in response to a noxious stimulus in 50% of subjects.

§  MAC is analogous to the plasma EC50 (concentration for 50% effect) for intravenous anesthetics.

the alveolar concentration of an anesthetic (Fa)

§   ventilation the first of five factors that govern the pulmonary inhaled anesthetic concentration

§   blood passing through the lung opposes the effect of ventilation by drawing anesthetic from the lung.

§   An increased inspired concentration of anesthetic decreases the effect of uptake (the concentration effect), and at 100% inspired concentration, uptake no longer opposes the effect of ventilation.

the alveolar concentration of an anesthetic (Fa)

§  Metabolism of anesthetics can increase uptake.

§  Anesthetic uptake may be enhanced by movement of anesthetic between tissues (intertissue diffusion)

§  Three factors determine uptake by blood: solubility (the blood-gas partition coefficient),

§  pulmonary blood flow (cardiac output),

§   the difference in anesthetic partial pressure between the lungs and venous blood returning to the lungs

The toxicity of inhaled anesthetics

§   Halothane, enflurane, isoflurane, and desflurane have been reported to induce liver injury in susceptible patients. halothane (20%) ≫ enflurane (2.5%) ≫isoflurane (0.2%) > desflurane (0.02%). Sevoflurane does not produce acylated protein adducts.

§   inorganic fluoride levels〈50umol/L, fluoride-associated renal injury has not been reported.

Common inhaled anesthetics

§   Nitrous oxide: weak inhaled anesthetic potency, have no significant effect on cardiac output, heart rate, and blood pressure. Clinical concentration 50%-70%, oxygen concentration must be higher than 0.3, so as to prevent hypoxemia. To prevent diffused hypoxemia,100% oxygen should be inhaled for 5-10 min after stopping nitrous oxide. increase the pressure of the sealed cavity.

§  Enflurane: higher inhaled anesthetic potency, have an effect on EEG, depress the cardiovascular system, depress the respiratory system, but have no irritation to the airway. To maintain anesthesia with a concentration 0.5%-2%, be careful to use on the patient with epilepsy.

§  Isoflurane: high inhaled anesthetic potency, mildly depress the cardiovascular system and the respiratory system,  have no irritation to the airway. To maintain anesthesia with concentration 0.5%-2% can be used for controlled hypotension.

§  sevoflurane: higher inhaled anesthetic potency, mildly depress the cardiovascular system,  severely depress the respiratory system,  have no irritation to the airway. To maintain anesthesia with a concentration of 1.5%-2.5%.

Intravenous Anesthesia

Intravenous anesthetics are administered via the intravenous route - that is, directly into the patient's bloodstream. This allows them to reach a therapeutic level quickly and affect the brain quickly.

Common intravenous anesthetics

§   Thiopental:  rapid onset of action and short duration, water-soluble barbiturate salts in alkaline solutions PH10-11, usual concentration 2.5%. action on the GABA receptor, decrease cerebral metabolism, depress the cardiovascular system,  the respiratory system, and the sympathetic system.

§   Side effect: larygospasm bronchospasm

§   Induction:4-6mg/kg

§   Treat convulsions:1-2mg/kg

§   Ketamine: significant analgesic effect; It usually does not depress the cardiovascular and respiratory systems, but it does possess some of the adverse psychological effects ;

§   dissociative anesthesia; increase ICP; increase in intraocular pressure; increase salivation; a bronchial smooth muscle relaxant

§   Induction:1-2mg/kg iv,duration 15-20min

§   Basel anesthesia:5-10mg/kg im for children ,duration 30min

§   Etomidate: Etomidate is used primarily for the induction of anesthesia, especially in elderly patients and patients who have a cardiovascular compromise. It has a rapid onset of effect and a rapid offset even after a continuous infusion. Prolonged infusion results in inhibition of adrenocortical synthesis. The major advantage of etomidate is its minimal effect on the cardiovascular and respiratory systems. It is associated with a high incidence of burning on injection, thrombophlebitis, and postoperative nausea and vomiting (PONV). The induction dose is 0.2 to 0.3 mg/kg.

§ propofol: propofol provides rapid onset and offset with context-sensitive decrement times of approximately 10 minutes when infused for less than 3 hours and less than 40 minutes when infused for up to 8 hours. Its mechanism of action of γ-aminobutyric acid (GABA). At therapeutic doses, propofol produces a moderate depressant effect on ventilation. It causes a dose-dependent decrease in blood pressure primarily through a decrease in cardiac output and systemic vascular resistance. A unique action of propofol is its antiemetic effect.

§    induction : 1 to 2 mg/kg

§    maintenance: infusion of 100 to 200 µg/kg/min.

Muscle relaxants

§   This class of drugs has its effect at the neuromuscular junction by preventing the effects of acetylcholine. Normally, when a nerve stimulus acts to contract a muscle, it releases acetylcholine. The binding of this acetylcholine to receptors causes the muscle to contract

Different Mechanism between nondepolarizing and depolarizing relaxants

§   Nondepolarizing muscle relaxants produce neuromuscular blockade by competing with acetylcholine for postsynaptic receptors.  Depolarizing ones produces prolonged depolarization that results in decreased sensitivity of the postsynaptic nicotinic acetylcholine receptor and inactivation of sodium channels so that the propagation of the action potential across the muscle membrane is inhibited.

Depolarizing muscle relaxants

§   Succinylcholine is the only available neuromuscular blocker with a rapid onset of effect and an ultrashort duration of action.

§   Induction:1-2mg/kg peak time:60sec

§   Side effect:sinus bradycardia; increase plasma potassium;increase intragastric pressure, increase ICP; increase in intraocular pressure

Nondepolarizing muscle relaxants

§   Pancuronium: onset time:3-6min;duration :100-120min; Induction:0.1-0.15mg/kg

§   Vecuronium: onset time:2-3min;duration :25-30min; Induction:0.07-0.15mg/kg

§   Rocuronium: onset time:1-1.5min;duration :25-30min; Induction:0.6-1.2mg/kg

§   Cisatracurium: onset time:2-3min;duration :50-60min; Induction:0.15-0.2mg/kg,hofmann elimination

Types of epidemiological studies: Cohort study

A cohort study is a type of observational investigation in which subjects are classified on the basis of the level of exposure to a risk factor and followed to determine subsequent disease outcomes.Cohort study characteristics

  1. Observational study: No manipulation of the study factors
rs

  2. Have a control group.

  3. From ‘cause’ to ‘outcome’.

l  “Prospective” = forward-looking in time

l  Can be a historical perspective

l  Also called follow-up, incidence, panel, or longitudinal study

  4. Could examine the causal association between the exposure and the outcome.

Cohort study types

1. Prospective cohort study: The basic type of cohort study

2. Historical cohort study Or retrospective cohort study

3. Ambispective cohort study

Prospective cohort studies

Prospective cohort studies are conducted by making all observations on exposure and disease status after the onset of the investigation

Retrospective cohort studies

Retrospective cohort studies involve observations on exposure and disease status prior to the onset of the study

Cohort Study design and practice

·         Selection of Subjects

       The Exposed Group

       The Unexposed Group

       The Outcome Event

l    Follow up

l    Data Collection

Selection of exposed group

Exposure determining is based on a descriptive study and case-control study. The degree of exposure may differ depending on the goals of the study.

The investigator should identify an accessible population that is motivated to participate in the study and unlikely to discontinue participation

When the purpose of a cohort study is to investigate a community, such as in the Framingham Heart Study that community is the source of the unexposed persons.

Data Collection

Possible sources of data an exposure status include records, Interviews or Questionnaires, or Direct Measurements Made on Cohort Members.

Records

The available records include Occupational records, medical and pharmacy records, census records and so on

Direct Measurements

Many exposures of interest cannot be determined with any accuracy, or perhaps at all, for individual study subjects from either records or interviews, but can be determined by direct measurement.

Cumulative incidence rate

A number of new cases of disease occurring over a specified period of time in a population at risk at the beginning of the interval.

Cumulative Incidence

the probability (risk) of an individual developing the disease (outcome) during a specific period of time.

Incidence density

A number of new cases of disease occurring over a specified period of time in a population at risk throughout the interval. The probability (risk) of an individual developing the disease (outcome) during a specific period of time, using total person-time as the denominator.  One subject followed one year contributes one person-year (PY). 

Incidence density requires us to add up the period of time each individual was present in the population and was at risk of becoming a new case of the disease.

                                                                               

Incidence density characteristically uses as the denominator person-years at risk.  (Time period can be person-months, days, or even hours, depending on the disease process being studied.)