AF control

The initial management of patients with AF and a rapid ventricular rate involves two decisions:

• Determining the urgency of initial therapy (eg, intravenous versus oral rate control therapy, and/or immediate versus elective cardioversion).
• Choosing between a rate control and a rhythm control strategy.

Rate vs rhythm - AFFIRM and RACE trial has shown that rate and rhythm control have similar outcomes.

Rate control

Beta-blockers, usually metoprolol. IV for acute control, oral for chronic control

Complications: worsening heart failure, bronchospasms(COPD), hypotension, reduced exercise tolerance.

CCB, usually verapamil. Verapamil increases refractoriness and decreases conduction velocity in the AV node. These drugs can be used intravenously for acute rate control and can produce long-term rate slowing when used orally.

Digoxin, lows the ventricular rate during AF primarily by vagotonic inhibition of AV nodal conduction. It is generally less effective for rate control than beta blockers or calcium channel blockers, particularly during exercise when vagal tone is low and sympathetic tone is high (see 'Comparative efficacy' below [10,17,18,34-39]. Furthermore, digoxin has no ability to terminate AF. In HF, increases contractility and reduction in ventricular rate.

Plasma digoxin levels should be monitored periodically. Although the correlation between drug concentration and ventricular rate control is poor, the presence of a low serum digoxin concentration is useful in that it allows a higher dose to be administered.

Junctional escape beats (detected by the equality of all of the longest observed R-R intervals on the electrocardiogram) are common when digitalis has successfully slowed the ventricular rate. Giving more digoxin in this setting will increase the degree of AV nodal block and produce periods of a regular junctional escape rhythm. The change from single junctional escapes to periodic junctional rhythm usually signifies the development of digoxin toxicity.

Rhythm control

Reversion to NSR - pharmacological or direct cardioversion

DC cardioversion is indicated in patients who are hemodynamically unstable, a setting in which the AF is typically of short duration. In stable patients in whom spontaneous reversion due to correction of an underlying disease is not likely, either DC or pharmacologic cardioversion can be performed (table 2 and table 3A-B). Electrical cardioversion is usually preferred because of greater efficacy and a low risk of proarrhythmia. The overall success rate (at any level of energy) of electrical cardioversion for AF is 75 to 93 percent and is related inversely both to the duration of AF and to left atrial size [13]. (See "Restoration of sinus rhythm in atrial fibrillation: Therapeutic options".)A number of antiarrhythmic drugs are more effective than placebo, converting 30 to 60 percent of patients [14]. Evidence of efficacy from randomized trials is best established for ibutilide, flecainide, dofetilide, propafenone, and amiodarone

No structural heart disesae - fleclanide
Structural heart disease - amiodarone or sotalol

How to sedate a patient.

Summary:

• For severely violent patients requiring immediate sedation, give a rapidly acting typical antipsychotic or benzodiazepine alone (droperidol or midazolam) or a combination of a typical antipsychotic and a benzodiazepine (eg, haloperidol and lorazepam).
• For patients with agitation from drug intoxication or withdrawal, give a benzodiazepine.
• For patients with undifferentiated agitation, we prefer benzodiazepines, but typical antipsychotics are a reasonable choice.
• For agitated patients with a known psychiatric disorder, we prefer typical antipsychotic agents, but atypical antipsychotics are a reasonable choice.

Therefore,

• Haloperidol (5mg IM) + lorazepam (2mg IM) /diazepam[Pref. IV or oral (5-10mg)/midazalam[ I.V.: Initial: 0.5-2 mg slow I.V. over at least 2 minutes; slowly titrate to effect by repeating doses every 2-3 minutes if needed; usual total dose: 2.5-5 mg; use decreased doses in elderly.]
• or olanzapine (S/L wafer)
• Consider resperidone.
  
• Haloperidol has been used effectively for many years to control violent and agitated patients [69,70]. It can be given IV, IM, or orally, although its IV use is not approved by the United States Food and Drug Administration (FDA). It is usually given in doses of 2.5 to 10 mg. The onset of action is within 30 to 60 minutes. The dose should be decreased by one half in the elderly. Some clinicians give repeat doses as frequently as every 15 to 20 minutes in patients with severe agitation until the desired level of sedation is achieved, but according to the manufacturer doses may be repeated every 30 minutes.
• Lorazepam is commonly used due to its rapidity of action, effectiveness, short half-life, and intramuscular (IM) or intravenous (IV) route of administration [58]. The usual dose is 0.5 to 2 mg IV or IM. Some experts give doses as frequently as every 10 minutes for severely agitated patients, although standard sources of drug information suggest a dosing interval of 30 minutes. The half-life of lorazepam is 10 to 20 hours.
• Olanzapine and risperidone are the preferred medications for acutely agitated geriatric patients with dementia [82]. However, deaths have been reported following such use and the US FDA has released an advisory [83,84]. In the elderly patient, the dose for these medications should be decreased.

Thalassemia

Beta thal

• hetergenous disease


• Mutations - B+ (decreased pdc), B0 (no pdc).


• Phenotype is variable - unidentified modifying genes


• Beta-minor - B/B+ or B/B0, usually asymptomatic, microcytic (MCV<>
• Beta-intermedia -symptomatic thal but able to survive to the 2nd decade with no chronic transfusion therapy
• Beta-major - B0/B0 or B+/B+
• Diagnosis — The diagnosis of beta thalassemia minor or intermedia should be entertained in patients of any age with microcytic, hypochromic red cells. the beta thalassemias show considerable heterogeneity, patients may or may not have symptoms referable to anemia, may have variable degrees of splenomegaly and variable degrees of hemolysis.

The major differential diagnosis in such patients includes iron deficiency and the anemia of chronic inflammation, as follows:

• Patients with iron deficiency will have low levels of serum iron and ferritin and increased levels of transferrin (total iron binding capacity). A cause for blood loss will be obvious in most patients.
• Patients with the anemia of chronic inflammation will have low levels of serum iron and transferrin. Levels of ferritin will be normal or increased. An inflammatory, infectious, or malignant disease is usually the underlying cause.
• Patients with thalassemia will have normal to increased levels of serum iron and ferritin. Levels of transferrin will be normal or decreased. At least one of the patient's parents will also be affected. A family history of "iron deficiency anemia" not responding to treatment with iron is common.

The diagnosis of a beta thalassemic condition is confirmed on hemoglobin electrophoresis (table 1 and table 3). Hemoglobin A will be the major hemoglobin present. Levels of hemoglobin A2 are increased in virtually all patients, while levels of hemoglobin F are increased in about 50 percent of patients.

If hemoglobin S is present on electrophoresis along with hypochromic, microcytic red cells, and iron deficiency is absent, one of the sickle cell/thalassemia conditions is present.

• Hb A - 2 alpha, 2 beta
• Hb A2 - 2 alpha, 2 delta
• Hb F - 2 alpha and 2 gamma

Alpha thal

• 4 functional genes. two on each chromosome
• Loss of 1 - alpha thal, silent carrier.
• Loss of 2 - alpha thal minor
• Loss of 3 - alpha thal major, hemoglobin H disease. moderate degree of anemia, their red cells are microcytic, and their hemoglobin electrophoresis pattern shows 5 to 30 percent hemoglobin H (beta-4 tetramers). Chronic hemolytic anemia.
  
• Loss of 4 - hydrops fetalis

Diagnosis —

• The peripheral blood film in Hb H disease shows hypochromia and microcytosis ( readily detectable inclusion .
• Bone marrow examination reveals erythroid hyperplasia with poorly hemoglobinized erythroblasts carrying inclusion bodies.
• The diagnosis of hemoglobin H disease is confirmed by finding Hb H in circulating red cells, in concentrations from 5 to 30 percent, using a number of hemoglobin electrophoretic or chromatographic techniques (table 1 and figure 1). In addition, Hb Barts (gamma-4), a fast-moving hemoglobin, can be detected in concentrations of about 20 to 40 percent at the time of birth of a child with hemoglobin H disease [55]. This latter test has been successfully employed in California as a screening test for hemoglobin H disease [61].
• DNA-based genotyping is required for precise diagnosis, and is especially important in prenatal testing and genetic counseling (see 'Genetic counseling and antenatal diagnosis' below).

DVT therapy and prophylaxis

Prophylaxis

• 40mg clexane DAILY or 5000units of heparin BD
• TED stockings
• early mobilisation

Therapy

• 1mg/kg/BD (half-dose if renally impaired)
• Heparin requires infusion