0.63 Mg by nebulizer q8h

Drug Category: Long-acting beta2-agonist

 Long-acting bronchodilators are not used for the treatment of acute bronchospasm. They are used for the preventive treatment of nocturnal asthma or exercise-induced asthmatic symptoms, for example. Currently, 2 long-acting beta2-agonists are available in the United States: salmeterol (Serevent) and formoterol (Foradil). Salmeterol is discussed below. Salmeterol is available as a combination of salmeterol and fluticasone (Advair) in the United States. Advair has an expiration date of 30 days once the protective wrapper is removed.

Salmeterol (Serevent Diskus) This long-acting preparation of a beta2-agonist is used primarily to treat nocturnal or exercise-induced symptoms. It has no anti-inflammatory action and is not indicated in the treatment of acute bronchospastic episodes. It may be used as an adjunct to inhaled corticosteroids to reduce the potential adverse effects of the steroids.

<12 years: Not established

>12 years: 1 inhalation of inhalation powder (50 mcg) q12h; data

                  in children are limited

Drug Category: Methylxanthines

These agents are used for long-term control and prevention of symptoms, especially nocturnal symptoms.

Theophylline (Theo-24, Theolair, Theo-Dur, Slo-bid) is available in short- and long-acting formulations. Because of the need to monitor the drug levels (see Precautions below), this agent is used infrequently.

Initial dose: 10 mg/kg PO sustained-release tablets and capsules; not to exceed 300 mg/d

 First dose adjustment: 13 mg/kg PO; not to exceed 450 mg/d

 Second dose adjustment: 16 mg/kg PO; not to exceed 600 mg/d

Drug Category: Mast cell stabilizers

  These agents block early and late asthmatic responses, interfere with chloride channels, stabilize the mast cell membrane, and inhibit the activation and release of mediators from eosinophils and epithelial cells. They inhibit acute responses to cold air, exercise, and sulfur dioxide.

Cromolyn sodium (Intal), nedocromil sodium (Tilade). These nonsteroidal anti-inflammatory agents are used primarily in preventive therapy.

Cromolyn: 20 mg in 2 mL nebulizer solution q6-8h

 Nedocromil: 2-4 inhalations bid/tid; 1.75 mg/actuation 

Intal - cromolyn sodium

   Tilade   - nedocromil

Drug Category: Corticosteroids

Steroids are the most potent anti-inflammatory agents. Inhaled forms are topically active, poorly absorbed, and least likely to cause adverse effects. No study has shown significant toxicity with inhaled steroid use in children at doses less than the equivalent of 400 mcg of beclomethasone per day. They are used for long-term control of symptoms and for the suppression, control, and reversal of inflammation. Inhaled forms reduce the need for systemic corticosteroids. They block late asthmatic response to allergens; reduce airway hyperresponsiveness; inhibit cytokine production, adhesion protein activation, and inflammatory cell migration and activation; and reverse beta2-receptor downregulation and subsensitivity (in acute asthmatic episodes with long-term beta2-agonist use).  

Inhaled steroids include beclomethasone, triamcinolone, flunisolide, fluticasone, and budesonide.

Beclomethasone (Beclovent, Vanceril, QVAR)  Inhibits bronchoconstriction mechanisms; causes direct smooth muscle relaxation; and may decrease the number and activity of inflammatory cells, which, in turn, decreases airway hyperresponsiveness.

Low dose: 84-336 mcg/d (42 mcg/oral inhalation, 2-8 inhalations q24h)

 Medium dose: 336-672 mcg/d (42 mcg/oral inhalations, 8-16

                     inhalations q24h)

 High dose: >672 mcg/d (42 mcg/oral inhalation, >16 inhalations q24h)

Fluticasone (Flovent) has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary adrenocortical axis inhibitory potency when applied topically.

Low dose: 88-176 mcg/d (44 mcg/oral inhalation, 2-4 inhalations q24h)

 Medium dose: 176-440 mcg/d (110 mcg/oral inhalation, 2-4 inhalations

 q24h)

 High dose: >440 mcg/d (110 mcg/oral inhalation, >4 inhalations q24h or 220

 mcg/oral inhalation, 2 inhalations q24h)

Budesonide (Pulmicort Turbuhaler or Respules)  Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary adrenocortical axis inhibitory potency when applied topically. Pulmicort is available in a powder inhaler (200 mcg per oral inhalation) or as a nebulized susp (ie, Respules).

MDI: Low dose: 100-200 mcg/d (1 inhalation q24h)

 Medium dose: 200-400 mcg/d (1-2 inhalation q24h)

 High dose: >400 mcg/d (>2 inhalations q24h)

 Nebulizer (inhalation susp): 0.25-0.5 mg bid; not to exceed 1 mg/d        

Drug Category: Systemic corticosteroids

 These agents are used for short courses (3-10 d) to gain prompt control of inadequately controlled acute asthmatic episodes. They are also used for long-term prevention of symptoms in severe persistent asthma as well as for suppression, control, and reversal of inflammation. Frequent and repetitive use of beta2-agonists has been associated with beta2-receptor subsensitivity and downregulation; these processes are reversed with corticosteroids.

Higher-dose corticosteroids have no advantage in severe asthma exacerbations, and intravenous administration has no advantage over oral therapy, provided that gastrointestinal transit time or absorption is not impaired. The usual regimen is to continue frequent multiple daily dosing until the FEV1 or PEF is 50% of the predicted or personal best values; then, the dose is changed to twice daily. This usually occurs within 48 hours.

Prednisone (Deltasone, Orasone) and prednisolone (Pediapred, Prelone, Orapred) -- Immunosuppressants for the treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

1-2 mg/kg/d PO for 3-10 d; not to exceed 60-80 mg/d 

Methylprednisolone (Solu-Medrol)  May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

1 mg/kg IV q6h 

Drug Category: Leukotriene modifier

 Knowledge that leukotrienes cause bronchospasm, increased vascular permeability, mucosal edema, and inflammatory cell infiltration leads to the concept of modifying their action by using pharmacologic agents. These are either 5-lipoxygenase inhibitors or leukotriene-receptor antagonists.

Zafirlukast (Accolate).  It is a selective competitive inhibitor of LTD4, LTE4 receptors.

5-11 years: 10 mg PO bid

 >12 years: Administer as in adults

 

Montelukast (Singulair)   It is a last agent introduced in its class. The advantages are that it is chewable, it has a once-a-day dosing, and it has no significant adverse effects.

12-23 months: 1 packet of 4 mg oral granules PO hs

 2-6 years: 4 mg PO hs

 6-14 years: 5 mg PO hs

 >14 years: Administer as in adults

Drug Category: Monoclonal antibody

  These agents bind selectively to human IgE on the surface of mast cells

and basophils.

Omalizumab (Xolair)  Recombinant, DNA-derived, humanized IgG monoclonal antibody that binds selectively to human IgE on surface of mast cells and basophils. Reduces mediator release, which promotes allergic response. Indicated for moderate-to-severe persistent asthma in patients who react to perennial allergens in whom symptoms are not controlled by inhaled corticosteroids.

<12 years: Not established

>12 years: 150-375 mg SC q2-4wk; inject slowly over 5-10 s because of viscosity; not to exceed 150 mg per injection site

 Precise dose and frequency established by serum total IgE level (IU/mL)

                                  ASTHMATIC STATE 

The asthmatic state is the attack of asthma, which lasts more than 6–10 hours and resistant to sympatomimetics and methylxantins. It is characterized by total bronchoobstruction on a background of refraction of b2-adrenoreceptors with progress of hypoxia, hypercapnia, decompensative acidosis, dehydration and development of acute cardiac insufficiency of a right-heart type. In the process of development of the asthmatic state three stages are selected: relative indemnification, decompensation and hypoxemic comma.

Diagnostic criteria of asthmatic status

1. Protracted attack of bronchial asthma, which is not cured during 6 hears

    and anymore.

2. Resistens to sympatomimetics.

3. Violation of drainage function of bronchial tubes.

4. Development hypoxemia -  РаО2  - 60 ml Hg, hypercarpnia - РаСО2  60 ml Hg.

                                         Clinic.

 I stage of the asthmatic status (relative compensation). Forced sitting  position, leaning against hands, tachypnoe with the considerably prolonged inspiration, attack cough with much amount of viscid phlegm which is badly deleted. Skinis pale, cyanosys of lips, nasolips triangle, acro- or general cyanosys. A thorax is emphysematous, the excursion  is limited, above lungs percussion box sound. Plenty of the  distance wheezes in comparisone with little amount of  dry wheezes, the loosened breathing in lungs. The border of heart is not determined, are low, systolic murmur on an apex, tachycardia. A liver is enlarged, sickly. Arterial pressure is decreased.

 

                      Help on prehospital stage

1.             Do not use of symdatomimetics!

2.             To provide access of fresh air.

3.             To release from squeezing clothes.

4.             Oxygentherapy:  moistened air through a mask.

5.             2,4 % solution of Euphyllini in dose of a 5 mg/kg of  mass of

                    intravenously streamly on a 15 –20 ml of isotonic  solution of sodium

                   chloride.

6.             2 % solution of No-spani a 1 mg/кг mass on dose intramuscular.

7.             3 % solution of Prednisoloni 2-3 mg/kg of the masses (Hydrocortisoni

                        10-15 mg/kg) intramuscular or intravenously streamly.

8.             Urgent hospitalization.

 

Help on a hospital stage

1.             Do not use sympatomimetics!

2.             To provide access of fresh air.

3.             Oxygentherapy optimum 40 % by the moistened oxygen constantly.

4.             3 % solution of Prednisoloni in dose 2-3 mg/kg of  the mass

                      intravenously streamly on a 5-10 ml of  isotonic  solution of sodium

                     chloride.

5.             2 % solution of No-spani  1 mg/kg of  mass on dose intramuscular

                     or intravenously streamly slowly.

6.             Solution of Corgliconi 0,06 % or Strophantini 0,05 % 0,1 ml per the year

                       of life, but not more than 0,3-0,4 ml on a 5-10 ml isotonic  solution of

                      sodium  chloride  intravenously streamly.

7.             Cocarboxylazae 50-100 mg, 5 % solution of sodium ascorbinati 2,0-5,0

                    ml, Panangini 0,5 ml per year of life of intravenously streamly in

                   separate syringe .

8.             2,4 % solution of Euphyllini 7-10 mg/kg of  mass on a 200 ml of isotonic

                      solution of sodium  chloride intravenously with a next continuous

                      tranfusion on Euphyllinization by intravenously infusion of 2,4 %

                      solution of Euphyllini at a speed of 0,7 mg/kg/hour on isotonic  solution

                     of sodium  chloride, but not more than 24 mg/kg/day for the children

                    upto 9 years and 20 mg/kg/day for children  senior than  9 years.

9.             Heparini 200-300 U/day on 4 intravenous stream injection every 6 hours.

10.        Reopoliglucini 150-200 ml intravenously in drops.

11.        In default of effect in 2 hours o repeate intravenous stream injection of

                     Prednisolone 2-3 mg/kg of  the masses or Hydrocortisoni 10-15 mg/kg

                    of  mass.

12.        Alkaline drink: mineral water, 1 % solution of soda, milk with a soda.

                    Intravenous  injection of 4 % solution of sodium bicarbonatis only under

                    the control of  acid – alkaline equilibrium indexes.

13.        Absence of effect after the repeated injection  of glucocorticoids testifies

                     to transition of the asthmatic state in the ІІ stage.

 

Clinic of the ІІ stage of the asthmatic status (decompensations). Child in consciousness, excited or apathetical. General cyanosis of skin and mucus, a person is puffy, the veins of neck are swelling. Breathing is encreased, noisy with the prolonged inspiration and acute downing in of interribs intervals, supraclavicular and epigastrial areas, jugular pit with a limited excursion of thorax. Percussion: bandbox sound. Breathing is sharply loosened with single unsounding dry wheezes, in the lower areas of lungs breathing is not listened, syndrome of “mute lungs”. Таhycardia, pulse of the weak filling, unrhythmical. The tones of heart are not determined, tones are deaf. Arterial pressure is reduced. A liver is enlarged, sickly.

Help on prehospital stage

1.             To provide access of fresh air.

2.             Oxygentherapy:  moistened air through a mask.

3.             2,4 % solution of Euphyllini in dose of a 5 mg/kg of  mass intravenously

                    streamly on a 15-20 ml of  isotonic  solution of sodium  chloride.

4.             3 % solution of Prednisoloni in dose of a 3-5 mg/kg of  mass or

                   Hydrocortisoni 15-25 mg/kg of  mass intramuscular or intravenously

                   streamly.

5.             Urgent hospitalization.

 

Help on  hospital stage

1.             To provide access of fresh air.

2.             Oxygentherapy: optimum 40 % of the moistened oxygen constantly

                     through a mask.

3.             3 % solution of Prednisoloni in dose of  3-5 mg/kg of  mass or

                   Hydrocortisoni  15-25 mg/kg of  mass of intravenously streamly with the

                   repeated introduction after 1,5-2 hours in default of effect.

4.             2 % solution of No-spani 1 mg/kg of mass in dose intramuscular or

                    intravenously streamly slowly.

5.             Solution of Corgliconi 0,06 % or Strophantini 0,05 % in dose 0,1 ml per

                     the year of life, but not more than 0,3-0,4 ml intravenously streamly on a

                     5-10 ml of  isotonic solution of sodium  chloride.

6.             Cocarboxylazae 50-100 mg, panangini 0,5 ml per year of life, 5 %

                    solution of  sodium  ascorbinati 2,0-5,0 ml intravenously streamly in

                    separate syringes.

7.             2,4 % solution of Euphyllini 7-10 mg/kg of mass on a 200 ml of isotonic

                    solution of sodium  chloride of intravenously in drops. If Euphyllini was

                   already entered at treatment of I stage of the asthmatic status, continue

                   Euphyllinization at a speed of 0,7 mg/kg/hour on isotonic solution of

                   sodium chloride 50 ml/ hour.

8.             Heparini 200-300 Units/kg/days, divided in 4 injections, every 6 hours

                      intravenously streamly.

9.             In default of effect after the repeated introduction of glucocorticoids

                    urgent intubation with bronchoscopy sanation and after that- artificial

                    ventilation.

10.        On artificial ventilation Euphyllinization must be continued, repeat

                    introductions of Prednisoloni every 1,5-2 hours in  dose of  6-10 mg/kg

                   of  mass.

11.        Mucolitic drugs endotrachially with the following lavagge of bronchial

                     tubes with bronchoscopy.

12.        Intravenously 4 % solution of sodium bycarbonatis only under the

                      control of indexes acid – alkaline equilibrium.

13.        Haemosorbtion, plazmopheresis. 

It is not recommended to enter:

1.Antihistaminic drugs – Suprastini,Tavegili, Claritini.

2.Sedative drugs – Seduxeni, Sodium oxytirati , Aminasini.

3.Drugs with ephedrini – Solutani, Broncholitini.

4.Unselective b2- -adrenomimetics - Astmopent, Alupent, Izadrin.

5.Prolonged b2- -adrenomimetics – Salmeterol, Seretid.

ATTACK OF BRONCHIAL ASTHMA IN CHILDREN

OF EARLY AGE

As a result of anatomo-physiologic features of breathing organs  in the children of early age  the pathophysiologic mechanisms of bronchoobstruction and  edema of mucus membrane of bronchial tubes and hypersecretion of bronchial glands come forward on the first plan. It is the reasone of  more gradual beginning and slow  development of disease, “moist” character of asthma, less efficiency of sympatomimetics.

Clinic. Trouble, crabbiness of child at the moderate phenomena of general intoxication and normal temperature of body. Cyanosis  of lips, nasolibs triangle, acrocyanosis. Dyspnoe, noisy, with the prolonged inspiration and   distance wheezes. Downing in of interribs intervals, supraclavicular areas, jugular pit. Attacks of underproductive, sometimes attack cough. A thorax is emphizematous, at percussion above lungs bandbox sound, at auscultation breathing is hard, with the prolonged inspiration and dissipated dry and different moist wheezes. Таchycardia. A liver is often enlarged. There can be eozinophylia in the general analysis of   blood, sometimes there is moderate neutrophyl leucytosis. On the X-ray examination of thorax organs pulmonary  picture is strengthening , areas of promoted pneumatisation without of infiltrative changes in lungs.

                            Further Inpatient Care

Admit patients for treatment of acute severe episodes if they are unresponsive to outpatient care (eg, they have worsening bronchospasm, hypoxia, evidence of respiratory failure).

Once the patient is admitted, further investigations (eg, PFTs, allergy testing, and investigations to rule out other associated conditions and complications) can be performed.

                                Further Outpatient Care

Regular follow-up visits (1-6-mo intervals) are essential to ensure control and appropriate therapeutic adjustments.

Outpatient visits should include the following:

Ø Interval history of asthmatic complaints, including history of acute episodes

Ø (eg, severity, measures and treatment taken, response to therapy)

Ø History of nocturnal symptoms

Ø History of symptoms with exercise and exercise tolerance

Ø Review of medications, including use of rescue medications

Ø Review of home-monitoring data (eg, symptom diary, peak flow meter

Ø readings, daily treatments)

Ø Patient evaluation should include the following:

Ø Assessment for signs of bronchospasm and complications

Ø Evaluation of associated conditions (eg, allergic rhinitis)

Ø Pulmonary function testing (in appropriate age group)

Ø Address issues of treatment adherence and avoidance of environmental

Ø triggers and irritants.

Long-term asthma care pathways that incorporate the aforementioned factors can serve as roadmaps for ambulatory asthma care and help streamline outpatient care by different providers.

In the author's asthma clinic, a member of the asthma care team sits with each patient to review the written asthma care plan and to write and discuss in detail a rescue plan for acute episode, which includes instructions about identifying signs of acute episode, using rescue medications, monitoring, and contacting the asthma care team. These items are reviewed at each visit.

Inpatient & Outpatient Medications

ü Bronchodilators (short- and long-acting)

ü Controlling medications (nonsteroidal, steroidal, newer agents such

             as leukotriene modifiers)

ü Medications for the treatment of associated conditions (antiallergy

               medications, nasal steroids for allergic rhinitis)

ü Rescue medications for use in acute episodes (short burst of steroids)

                              Transfer

         Any patient with a high risk of asthma should be referred to a specialist. The following may suggest a high risk:

§  History of sudden severe exacerbations

§  History of prior intubation for asthma

§  Admission to an ICU because of asthma

§  Two or more hospitalizations for asthma in the past year

§  Three or more emergency department visits for asthma in the past year

§  Hospitalization or an emergency department visit for asthma within the

§  past month

§  Use of 2 or more canisters of inhaled short-acting beta2-agonists per month

§  Current use of systemic corticosteroids or recent withdrawal from

       systemic corticosteroids

The choice between a pediatric pulmonologist and an allergist may depend on local availability and practices. A patient with frequent ICU admissions, previous intubation, and a history of complicating factors or comorbidity (eg, cystic fibrosis) should be referred to a pediatric pulmonologist. When allergies are thought to significantly contribute to the morbidity, an allergist may be helpful.

 

Prevention

The goal of long-term therapy is to prevent acute exacerbations.

The patient should avoid exposure to environmental allergens and irritants that are identified during the evaluation.

Complications

§  Pneumothorax, status asthmaticus with respiratory failure

§  Fixed (nonreversible) airway obstruction

§  Death 

Prognosis

Of infants who wheeze with URTIs, 60% are asymptomatic by age 6 years; however, children who have asthma (recurrent symptoms continuing at age 6 y) have airway reactivity later in childhood.

Some findings suggest a poor prognosis if asthma develops in children younger than 3 years, unless it occurs solely in association with viral infections.