management of acute asthma in adults

1. ”ق الوا سبحانك لا علم لنا إلا ما
علمتنا إنك أنت العليم الحكيم ”
صدق الله العظيم ) البقرة – 32 )
بسم الله الرحمن الرحيم

2. Emergency Department and Hospital Management Protocol

4. ACUTE ASTHMA
Gaps in knowledge and care

5. §Exacerbations of asthma are episodes of progressive increase in shortness of breath, cough, wheezing, or chest tightness or some combination of these symptoms.
§Severe asthma exacerbations are potentially life-threatening medical emergencies and treatment requires close supervision
Asthma Exacerbations

6. § It is essential that GPs know how to manage acute asthma and regard each emergency asthma consultation as acute, severe asthma until proven otherwise.
§10 – 25% of ED patients with acute asthma require admission
Asthma Exacerbations

7. §Emergency management is the management plan for acute exacerbation of asthma.
§Severe acute asthma should always be dealt on emergency basis.
§Acute exacerbation of asthma may appear in any class or variant of asthma
Asthma Exacerbations

8. §Acute attacks of asthma may come on suddenly
§Acute attacks of asthma may occur in patients with well-controlled asthma, but usually are an indication of failure of the long-term management plan.
§Acute severe asthma is one of the most common medical emergency situations in childhood
Asthma Exacerbations

9. Severe asthma
7%
Clinical
respiratory
infections
15%
Acute exposure to
allergens or other triggers
14%
Poor asthma
control
(inadequate
treatment)
64%
% OF SUBJECTS WITH ED ADMISSIONS
BY CAUSES OF ASTHMA ATTACK
EMERGENCY VISITS FOR ASTHMA
Policlinico San Matteo, Pavia 2002
Cerveri et al. ATS 2004

10. §Initiation of appropriate therapy at the earliest possible signs of deteriorating control of asthma is important in the successful management of asthma exacerbations
§ It is estimated that 75% of hospital admissions and 90% of asthma deaths are preventable.
Asthma Exacerbations

11. §The severity of asthma exacerbations may range from mild to life threatening.
§Deterioration usually progresses over hours or days, but may occasionally occur precipitously over some minutes.
Asthma Exacerbations

12. •Type 1 or slow onset acute asthma.
• Type 2 or sudden-onset asthma attack (asphyxic or hyperacute asthma)
Asthma Attack Evolution

13. Triggers of asthma exacerbation
1. Viral upper respiratory tract infections
2. Allergen exposure
3. Environmental pollutants
4. Occupational sensitisers/irritants
5. Smoking
6. Medications : e.g aspirin

14. Allergens
Respiratory Viral Infections
Occupational Agents
Asthma Flare
Exercise Stress
Irritants
Smoke
Aspirin
Sulfites

15. §VRIs are recognized as a major cause of wheezing in all age groups and as a major cause of exacerbations in those with established asthma.
§Evidence has shown VRIs to be the cause of asthma exacerbations in approximately 80% of children and in 60% to 80% of adults.
Role of VRIs in Asthma Exacerbations

16. Risk factors for death from Asthma

17. THE DYING ASTHMATIC
•Risk factors for death
–Asthma history
Previous severe asthma, intubation or ICU admit
Lack of an a written asthma action plan
≥ 2 admissions OR ≥ 3 ED visits in last 12 months
Using > 2 Ventolin canisters per month
Admission or ED visit in last month
Difficulty perceiving asthma symptoms
3 or more classes of asthma medication
Current use of oral steroids or recent withdrawal from oral steroids

18. THE DYING ASTHMATIC
•Risk factors for death
–Adverse Psychosocial Factors
Non-compliance
Obesity
Self-discharge
Social isolation
Failure to attend appointments
Learning difficulties
Alcohol or drug abuse
Denial
Major tranquilliser use
Unemployment
Low socioeconomic status
Severe domestic, marital or legal stress.

19. THE DYING ASTHMATIC
•Risk factors for death
–Co-morbid conditions
Cardiovascular disease (CHF)
Other chronic lung disease (COPD)
Chronic psychiatric disease(Psychosis, depression, Deliberate Self Harm)
Intellectual Disability

20. •Patients who are at high risk for asthma-related death require special attention
–Such patients should be counseled to seek medical care early during an exacerbation and instructed about the availability of ambulance services.
–The level of asthma severity does not correlate with the likelihood of sudden-death asthma

21. §Do not underestimate the severity of an attack; severe asthma attacks may be life threatening. Their treatment requires close supervision.
§There are no clinical markers to identify individuals at risk for sudden onset of a near-fatal asthma exacerbation

22. What is
Happening…
Swelling (inflammation),
which makes the airways smaller
and harder for air to go through.
Tightening (constriction)
of the muscles around the
airways, making them smaller.
Too much mucus
is made, trapping the air.
Asthma Episode

25. Triggers
ß-agonist therapy
Inflammatory response
Bronchoconstriction, Airway edema
V/Q Abnormalities
Increased mucus
Airway obstruction
Hypoxemia
Increased work of breathing
Fatigue
CO2retention

27. Acute Asthma in Adults
•Most patients who present with an acute asthma exacerbation have chronic uncontrolled asthma
•The following should be carefully checked:
1.Previous history of near fatal asthma
2.Patient taking three or more medications
3.Heavy use of SABA and frequent ER visits
•Patient should be assessed to determine the severity of acute attacks
•PEF and pulse oximetry measurements are complementary to history taking and physical examination

28. Initial Monitoring
−Pulse oximetry
−PEFR (best of three)
−Pulse, BP
−RR
−1-2 word dyspnea
−Clinical judgement:
oCyanosis
oUse of accessory muscles
oDiaphoresis
oAnxious
−Blood gasses
Know Your Warning Signs!

29. •Wheezing is an unreliable indicator of the severity of an asthma attack and may be absent in a severe attack (Silent chest).
•Cyanosis indicates life-threatening asthma

30. Patient assessment
Clinical features
Clinical features, symptoms, respiratory and cardiovascular signs helpful but non-specific for severity; absence does not exclude severe attack
PEF or FEV1
Measurement of severity and guide for treatment. PEF more convenient. (PEF as %age previous best or predicted)
Pulse oximetry
Determines adequacy of oxygen therapy and need for ABG. Aim to maintain sats >92%
Blood gasses
Necessary for patients with SaO2 < 92% or if features of life threatening asthma
Chest
X-ray
Not routinely recommended in the absence of :-
•Suspected pneumomediastinum or pneumothorax
•Suspected consolidation
•Life threatening asthma
•Failure to respond to treatment as expected
•Requirement for ventilation
Systolic paradox
Systolic paradox (pulsus paradox)is an inadequate indicator of the severity of an attack and should not be used

31. § Are characterized by decrease in expiratory airflow (PEF or FEV1), are more reliable indicators of the severity of airflow limitation than is the degree of symptoms.
§The degree of symptoms may be a more sensitive measure of the onset of an exacerbation the increase in symptoms usually precedes the deterioration in peak flow rate.
Asthma Exacerbations

32. ABG
The 4 stages of blood gas progression in status asthmaticus are : The 1st stage is characterised by hyperventilation with a normal pO2 and low pCO2 The 2nd stage has hyperventilation but hypoxemia so that both pO2 and pCO2 are low The 3rd stage gives a "false-normal" pCO2 as ventilation has decreased. This is extremely serious and indicates respiratory muscle fatigue with the need for admission to the ICU and, probably, intubation with mechanical ventilation The 4th stage has a low pO2 and a high pCO2 as respiratory muscles fail. This is even more serious and requires intubation and ventilatory support

33. SlightModerateAcute severe asthma monitoringSeverethe cross-road of deathSlightModerateSevereNormo- ventilationHyper- ventilationHypoventilationExhaustionRHONCHI

34. ABG
Those in the first 2 stages do not necessarily require hospital admission if 1 hour after initial therapy the PF is at least 75% of predicted or best (Evidence level C). Poorer response or any risk factors should require admission The 3rd and 4th stages require admission to ICU

35. Hypoxemia and the increased work of breathing may result in anaerobic muscle work and accumulation of lactate.
During an asthma attack, metabolic acidosis may initially be compensated for by hyperventilation and a respiratory alkalosis
But as respiratory failure develops, increasing arterial CO2 will result in a respiratory acidosis and a further decrease in arterial pH Increasing levels of CO2 is a ominous sign Hypocarbia → Normal PCO2 = trouble
ABG

36. Levels of severity of acute asthma exacerbations in adults

37. Life-threatening asthma has the following features:
oPEFR less than 33% predicted
oO2 saturation below 92%
oArterial partial pressure O2 (<8 kPa, <60mmHg)
oNormal arterial partial pressure CO2 (4.6-6 kPa, 35- 45 mmHg) or High PaCO2 >45mmHg
oSilent chest
oGyanosis
oFeeble respiratory effort
oBradycardia
oDysrythmia
oHypotension
oExhaustion
oConfusion
oComa
If any of these features are present, immediate hospital admission is mandatory.

38. •Remember that patients with severe or life- threatening attacks may not be distressed and may not have all the clinical symptoms and signs listed. The presence of any should alert the doctor.
√Admit the patient to hospital immediately if:
1.Any life-threatening features are present
2.There are features of acute severe asthma present after initial treatment or
3.The patient has had a previous episode of near- fatal asthma

39. Basic treatment of acute asthma

40. Key Points
Important elements:
–Early treatment is best.
–Recognition of early signs of worsening asthma
–Prompt communication between patient and clinician about: Serious deterioration in symptoms or peak flow Decreased responsiveness to inhaled beta2-agonists Decreased duration of beta2-agonist effect

41. Emergency Department and Hospital Management: Goals Correction of significant hypoxemia Rapid reversal of airflow obstruction Reduction of likelihood of recurrence

42. Manage Asthma Exacerbations
Primary therapies for exacerbations: Repetitive administration of rapid-acting inhaled β2-agonist Early introduction of systemic glucocorticosteroids Oxygen supplementation

44. –Oxygen
•Supplemental oxygen is recommended for all patients
–Maintain O2 saturation > 90% (BTS > 92%)
–> 95% in pregnancy or co-morbid heart disease
–Recent guidelines recommend that oxygen saturation in children should be kept above 95%
Basic treatment of acute asthma

45. Oxygen
Oxygen must be considered as a drug in a situation of acute asthma
– reducing hypoxic pulmonary vasoconstriction
– ventilation-perfusion mismatch All patients with acute severe asthma are hypoxaemic and require oxygen. This should be given via a face mask in a concentration high enough to maintain an adequate arterial oxygen saturation.

46. Oxygen at a rate of 6-8 litres per minute should be used to deliver nebulised drugs. In severe cases, oxygen should be administered before other drugs and before assessment is completed Oxygen should be the initial therapy for acute severe asthma in all health care settings Oxygen saturation should be monitored until a clear response to bronchodilator therapy has occurred

47. The risk of significant carbon dioxide retention is low except in life threatening attacks. The risk of hypercarbia and CO2 narcosis is more in COPD rather than acute severe asthma and in such cases assisted ventilation is required. Sedatives may precipitate the CO2 retention not only in patients with COPD but also in asthma Administration of sedatives and tranquilizers must be avoided.

48. Is oxygen necessary?
In the hospital and ambulance, all nebulised medications tend to be administered with oxygen, in cases of severe asthma it is likely that the patient is hypoxic and requires oxygen therapy.
More importantly, in these cases the use of bronchodilators can cause pulmonary vasodilation and this can result in increased blood flow to areas of poorly ventilated lung.

49. Is oxygen necessary?
Gas exchange may worsen temporarily after bronchodilator therapy This change in pulmonary blood flow caused by the bronchodilators, increases pulmonary ‘shunting’ and this can worsen the patient’s hypoxia. For this reason, oxygen should always be used both during and after bronchodilator therapy in severe asthma.

50. High concentration of inspired oxygen to correct hypoxemia (do not miss COPD) Pulse oximetry should be used to tailor oxygen therapy Failure to achieve oxygen saturations of more than 92% is a good predictor of the need for hospitalization Normal or high PaCO2 is an indication of a severe attack, and need for specialist consultation
Key Points

51. Bronchodilators
b2-agonists
Anticholinergic
drugs
Smooth
muscle
relaxation
Stimulates
b2-adrenergic
receptors of bronchi
reduce tonus
of vagus
Methylxanthines
inhibit phosphodiesterase

52. Short acting Beta2 Agonist
•Mainstay of therapy
•Rapid onset
•Selective b 2:
–Albuterol
–Terbutaline
•Mode of delivery:
–inhaled vs systemic
–intermittent vs continuous
–pMDI with Spacer vs Nebulizer

53. Short acting Beta2 Agonist Albuterol is the inhaled β2-adrenergic agonist most widely used for emergency management Repeated doses is recommended at 15–30 minute intervals. Alternatively, continuous nebulization (Salbutamol at 5–10 mg/hour) may be used for one hour if there is an inadequate response to initial treatment.

54. SABA treatment is recommended for all patients
The repetitive or continuous administration of SABAs is the most effective means of reversing airflow obstruction In the ED, three treatments of SABA spaced every 20–30 minutes can be given safely as initial therapy. Thereafter, the frequency of administration varies according to the improvement in airflow obstruction and associated symptoms and the occurrence of side effects.

55. Oral or parenteral administration of β2-adrenergic agonists is not recommended, since neither has been shown to be more effective than inhaled β2-adrenergic agonists, and both are associated with an increased frequency of side effects

56. Efficacy of the Inhaled Route
- nebulizer
- gas flow
- driving gas

57. 57
Deposition of particles
> 5 μ impaction
1-5 μ sedimentation
< 1 μ like gas

58. 58
1 – 5
Upper / central airways
Clinical effect
Subsequent absorption from lung
< 1
Peripheral airways / alveoli
Some local clinical effect
High systemic absorption
> 5
Particle size (microns)
Regional deposition
Efficacy
Safety
Mouth / oesophageal region No clinical effect
Absorption from GI tract if swallowed

59. How MDI Technology Works

60. 60
Oropharynx
absorbtion
Lung absorbtion
Vena porta
Hepatic inactivation
Gastrointestinal
absorbtion
SYSTEMIC CIRCULATION
Urine elimination
first pass effect
PHARMACOKINETICS OF INHALED DRUGS

61. Advantages of the Inhaled Route Direct respiratory tropism Short onset of action Low doses Less side-effects Simultaneous O2 delivery Humidification of the airways

62. Guidelines on Nebulizer Therapy (British Thoracic Society, Thorax 1997) Driving gas (SpO2 > 90%):
–Air + simultaneous O2 (nasal prong)
–O2 Fill volume of 4 mL (if residual volume > 1 mL) Flow rate 6-8 L/min Nebulization time < 10 min

63. Oxygen-driven nebulisers are preferred for nebulising β2 agonist bronchodilators because of the risk of oxygen desaturation while using air-driven compressors In hospital, ambulance and primary care, nebulised B2 agonist bronchodilators should be driven by oxygen. A flow rate of 6 l/min is required to drive most nebulisers.

64. √The standard regimen for initial care in the emergency department has become SABA nebulised, e.g. salbutamol with O2 8 L/min Salbutamol 1 mL of 5 mg/mL solution + 3 mL saline every 15-30 mins, then 2.5 to 10 mg every one to four hours as needed For critically ill patients, some clinicians prefer continuous nebulization, administering 10 to 15 mg over one hour might be more effective than intermittent administration

65. Dose distteld water can be used in nebulizer jet..?
Don't use distilled water for any reason. It has all of the mineral content removed, making it a virtual sponge that soaks up minerals and nutrients in the body, causing dehydration Saline is a much better "wetting" agent than just water The use of isotonic nebulized saline can be used to enhance expectoration, or mucous removal - Isotonic nebulized saline can be used to humidify airways.

66. 66
MDI spacer
Decrease of oropharyngeal deposition

67. ©2004 Children’s Hospital and Health System / FAM Allies. All rights reserved.
©1998, Respironics Inc.
©1998, Respironics Inc.
Without spacer
With spacer
S

68. Meter-Dose Inhalers with Holding Chambers As effective as nebulizers (Cates et al. Cochrane Database Syst Rev, 2000)
–Similar hospital admission rate
–Similar improvement in PEFR and FEV1
–Children:
• HR more important
• duration of the treatment in the ED Progressive administration of the medication Interesting for children < 3 years

69. Spacer versus Nebulizer
In acute asthma without life threatening features, β2 agonists can be administered by repeated activations of a pMDI via an appropriate large volume spacer or by wet nebulisation driven by oxygen, if available. In acute asthma with life threatening features the nebulised route (oxygen-driven) is recommended

70. Continuous administration of SABA may be more effective in more severely obstructed patients There is evidence suggesting that continuous administration of nebulised β2-agonists may have a better and prolonged bronchodilatory effect compared to intermittent therapy A sustained stimulation of β2-receptors is accomplished, and a possible rebound bronchoconstriction reported during intermittent therapy is prevented

71. Metered dose inhalers with a spacer produce outcomes that are at least equivalent to nebuliser therapy in severe asthma As a guide, 400 mg salbutamol via a spacer can be considered equivalent to a 2.5 mg dose of salbutamol via nebuliser.
If nebulizer is not available :

73. If nebulizer is not available :
The use of a metered-dose inhaler with a valved holding chamber is as effective as the use of a nebulizer Salbutamol 8-12 puffs via MDI (100 mcg/dose) is equivalent to 5 mg via nebulizer B2-agonists can be given through meter dose inhaler via spacer. Here 4-8 puffs given initially then at 5-20 minutes interval up to 4 hours, then it is given 1-4 hourly

74. Rapid-acting inhaled β2-adrenergic bronchodilators are first-line therapy for acute asthma.
Because the optimal doses necessary to achieve maximal bronchodilation have not been defined, dosing is empiric and should be titrated using an objective measure of airflow obstruction, such as FEV1 or peak expiratory flow and clinical response The heart rate usually falls with successful response to high doses of β2-adrenergic bronchodilators in this setting.

75. Rapid-acting inhaled β2-adrenergic bronchodilators remain effective for patients who have self-treated unsuccessfully with the same agents before arrival in the emergency department. For patients with acute asthma, the inhaled route for bronchodilators is as good as or better than giving the same drugs intravenously

76. In moderate to severe acute asthma, combining ipratropium bromide with Salbutamol has some additional bronchodilation effects, in reducing hospitalizations and greater improvement in PEF or FEV1
Anticholinergic Agents

77. Because of its relatively slow onset of action, inhaled ipratropium is not recommended as mono-therapy in the emergency department but can be added to a short-acting β2-adrenergic agonist for a greater and longer-lasting bronchodilator effect
Anticholinergic Agents

80. The adult dosing of ipratropium for nebulization is 500 mcg every 20 minutes for three doses, then as needed. Alternatively, ipratropium can be administered by MDI at a dose of eight inhalations every 20 minutes, then as needed for up to three hours 0.25–0.5 mg nebulizer solution or 4–8 puffs by MDI in children
Anticholinergic Agents

81. Add nebulised ipratropium bromide (0.5 mg 4-6 hourly) to β2 agonist treatment for patients with acute severe or life threatening asthma or those with a poor initial response to β2 agonist therapy Anticholinergic treatment is not necessary and may not be beneficial in milder exacerbations of asthma or after stabilisation

82. •Each unit dose vial contains ipratropium bromide (as ipratropium bromide monohydrate) 0.50 mg and salbutamol 2.5 mg (as salbutamol sulphate) in a 2.5 mL isotonic preservative-free solution for inhalation.
Combivent UDV
(Ipratropium - Salbutamol inhalation solution)

87. •Magnesium Sulphate
–Single dose beneficial in acute severe asthma
–Improves pulmonary function in patients with PEFR < 25% predicted
»Dose: Adult 2g IV over 15-20 minutes
»Dose: Child 25 – 75 mg/kg up to 2g Adjuvant therapies

88. Magnesium sulphate A single dose of IV magnesium sulphate (1.2–2 gm IV infusion over 20 mins) is safe and effective Routine use of IV magnesium sulphate in patients with acute asthma presenting to emergency department is not recommended. Its use should be limited to those with in those with life-threatening exacerbations and those whose exacerbations remain severe after 1 hour of intensive conventional Treatment

89. Magnesium is an airway smooth muscle relaxant. There is some evidence that, in adults, it has bronchodilator effects. Magnesium appears safe when given by the IV or nebulised route A single dose of IV magnesium sulphate is safe and may improve lung function in patients with acute severe asthma. Repeated doses could cause hypermagnesaemia with muscle weakness and respiratory failure.
Management of acute asthma BTS 2009

90. IV magnesium sulphate (1.2-2 g IV infusion over 20 minutes) should only be used following consultation with senior medical staff Intravenous magnesium has an excellent safety profile; however, it is contraindicated in the presence of renal insufficiency, heart block and hypermagnesemia can result in muscle weakness
Management of acute asthma BTS 2009

91. •In patients with acute asthma, isotonic magnesium sulfate, as a vehicle for nebulized salbutamol, increased the peak flow response to treatment in comparison with salbutamol plus normal saline
•Use of isotonic magnesium as an adjuvant to nebulised salbutamol results in an enhanced bronchodilator response in treatment of severe asthma (Lancet. 2003 June)
Inhaled MgSO4

92. Inhaled MgSO4
•Inhaled MgSO4 is more effective than placebo as a bronchodilator, but performs no better than salbutamol and there is no apparent synergy when the two are combined.
•Summary: Evidence suggests that intravenous MgSO4 is beneficial in acute asthma, while the evidence for inhaled MgSO4 is less convincing. Moreover, the role of replacement therapy with oral magnesium remains to be clarified

93. •Inhaled MgSO4 when combined with β2-agonists (usually salbutamol), improved pulmonary function but did not reduce the number of hospital admissions.
•Evidence has suggested that adding ipratropium bromide to β2-agonist therapy is effective in improving pulmonary function and in reducing the number of hospital admissions in the acute setting, especially in severe cases of acute asthma.
•The additive benefit of MgSO4 in the face of combination therapy with ipratropium bromide and β2-agonists remains unclear.

94. •Whereas intravenous MgSO4 treatments appear to be effective, long-term 'replacement' therapy with magnesium does not appear to affect chronic asthma.
•Magnesium deficiency is a common electrolyte disorder in patients with acute severe asthma, but intracellular magnesium content better reflects its homeostasis than does its serum concentration.
•There currently is no proof that using dietary magnesium supplements has a beneficial effect in asthma treatment.

95. Intravenous Aminophylline
•In acute asthma, the use of intravenous aminophylline did not result in any additional bronchodilation compared to standard care with B2-agonists
•Increases side effects with no additional bronchodilation
•NO LONGER INDICATED IN ADULTS

96. “Methylxanthines are NOT generally
recommended.”
-Expert Panel, NAEPP

97. The use of IV aminophylline, in addition to beta- agonists, is not recommended in the treatment of acute exacerbations. These agents are not as potent as the beta agonists when used alone for the treatment of asthma , and provide no further bronchodilation beyond that achieved with inhaled beta agonists alone In addition, these agents appear to increase the incidence of adverse effects when combined with bronchodilators

98. In acute asthma, IV aminophylline is not likely to result in any additional bronchodilation compared to standard care with inhaled bronchodilators and steroids. Use IV aminophylline only after consultation with senior medical staff. Some patients with near-fatal asthma or life threatening asthma with a poor response to initial therapy may gain additional benefit from IV aminophylline (5 mg/kg loading dose over 20 minutes unless on maintenance oral therapy, then infusion of 0.5-0.7 mg/kg/hr). Such patients are probably rare
Management of acute asthma BTS 2009

99. This drug has a narrow therapeutic margin and can cause substantial toxic effects, especially among hypoxemic patients If IV aminophylline is given to patients on oral aminophylline or theophylline,, determine serum theophylline concentration to prevent theophylline toxicity Levels should be checked daily for all patients on aminophylline infusions

100. Systemic Corticosteroids
In the ED, according to Current guidelines early systemic corticosteroids should be administered to all patients with moderate-to-severe exacerbations and to those who do not respond to initial B2-agonist therapy Systemic corticosteroids are recommended for most patiens because they speed the resolution of airflow obstruction and reduce the rate of post-ED relapse The earlier they are given in the acute attack the better the outcome

101. Administration The optimal dose for systemic glucocorticoids in asthmatic exacerbations the equivalent of a prednisone dose of 40 to 60 mg per day in a single or divided dose .
Daily doses of systemic glucocorticosteroids equivalent to 60-80 mg methylprednisolone as a single dose, or 300-400 mg hydrocortisone in divided doses, are adequate for hospitalized patients.
GINA 2008

102. IV and oral corticosteroids (CS) appear to have equivalent effects in most patients with acute asthma
There is a tendency toward greater and more rapid improvement in pulmonary function with medium (parenteral hydrocortisone, 100 mg q6h) and high doses (200 mg q6h), although these effects likely plateau without additional benefit at very high dosing.

104. Steroid tablets are as effective as injected steroids, provided they can be swallowed and retained.
Prednisolone 40-50 mg daily or parenteral hydrocortisone 400 mg daily (100 mg six-hourly) are as effective as higher doses higher doses do not seem to confer added advantage For convenience, steroid tablets may be given as 2- 3 x 20 mg tablets daily rather than 8-12 x 5 mg tablets. Continue prednisolone 40-50 mg daily for at least five days or until recovery.

105. The duration of a systemic therapy necessary to effect complete resolution of symptoms and return of lung function to baseline varies from patient to patient and attack to attack. As a rough guide, most severe attacks that require hospitalization will resolve (with return of lung function to baseline) in 10 to 14 days

106. The total course of systemic corticosteroids for an asthma exacerbation requiring an ED visit of hospitalization may last from 3 to 10 days. For corticosteroid courses of less than 1 week, there is no need to taper the dose. For slightly longer courses (e.g., up to 10 days), there probably is no need to taper, especially if patients are concurrently taking ICSs. ICSs can be started at any point in the treatment of an asthma exacerbation
EPR3

107. Finally, tapering oral glucocorticoids is not necessary if the duration of glucocorticoid treatment is less than three weeks (a duration too brief to cause adrenal atrophy) or if inhaled glucocorticoids are concomitantly prescribed for ongoing therapy (to prevent relapse) Give supplemental doses of oral corticosteroids to patients who take them regularly, even if the exacerbation is mild

108. Oral glucocorticosteroids require at least 4 hours to produce clinical improvement The time delay observed between administration and improvement in lung function or hospital admissions is consistent with belief that the beneficial effect of CS result from changes in gene transcription and altered protein synthesis (genomic effect)

109. Mechanism of Action for Steroid Hormones
Blood vessel Cell membrane
Nucleus
DNA Endoplasmic reticulum

110. Mechanism of Action for Steroid Hormones Carrier protein Steroid hormone

111. Mechanism of Action for Steroid Hormones
Steroid receptor

112. Mechanism of Action for Steroid Hormones
Transcription of mRNA

113. Mechanism of Action for Steroid Hormones
Translation of new protein
New protein produces change in cellular activity

116. Rapid nongenomic effect Opposed, there is evidence that suggests that inhaled corticosteroids can present early therapeutic effects This rapid response suggests a topical effect (airway mucosa vasoconstriction). Locally applied corticosteroids act by potentiating the adrenergic physiologic effect by up-regulating postsynaptic receptors.

117. Conclusions:
Data suggests that ICS present early beneficial effects (1 to 2 h) when they were used in multiple doses administered in time intervals < 30 min over 90 to 120 min.
The nongenomic effect is a possible candidate by covering the link between molecular pathways and the clinical effects of corticosteroids. (CHEST 2006)

118. Proposed mechanism of the acute vasoconstrictor effect of ICS in the airway. CS facilitate the sympathetic neuromuscular signal transmission by rapidly (within 5 min) inhibiting the extraneuronal monoamine transporter (EMT) in vascular smooth-muscle cells.

120. Variables
GENOMIC
NONGENOMIC
Receptor location
Cytoplasm
Membrane
Onset
Slow (h to d)
Rapid ( s to min)
Actions
Regulation of inflamatory gene transcription
Inhibition of local catecholamines disposal
Target-effects
Hyperperfusion 
Hyperpermeability
Leukocyte recruitment:
inhibition
Hyperperfusion 
Rodrigo G,Chest 2006;130;1301-1311

123. •The following agents have been used in investigational and selective cases –
Inhaled diuretics (Nebulized Lasix)
There is currently insufficient evidence to support the routine addition of nebulised furosemide to standard beta agonist therapy in acute asthma in adults
Inhaled heparin

124. Emergency Department and Hospital Management
Not generally recommended: Methylxanthines Antibiotics (except for patients with pneumonia, bacterial sinusitis) “Aggressive” hydration Chest physical therapy
Not recommended: Mucolytics Sedation

125. Antibiotics
Viral infection is the usual cause of asthma exacerbation The role of bacterial infection has been probably overestimated, and routine use of antibiotics is strongly discouraged They should be used when there is associated pneumonia or bacterial bronchitis

126. Antibiotic therapy is not routinely indicated for patients with acute severe asthma unless pneumonia or other evidence of bacterial infection is present. Clinicians must be aware that in patients with asthma, the presence of purulent sputum may not indicate infection but may be due to eosinophils in respiratory secretions
Antibiotics

127. “Aggressive” hydration
Contrary to common belief, patients who have acute severe asthma are not typically dehydrated, and intravenous fluids should be administered only if clinically indicated. Moreover, there is no evidence that intravenous fluids alter the consistency or viscosity of sputum in asthmatic persons or promote its clearance

128. Aggressive hydration is not recommended for older children and adults but may be indicated for some infants and young children .
Intravenous or oral administration of large volumes of fluids does not play a role in the management of severe asthma exacerbations.

129. ●Mucolytics are not recommended . Avoid mucolytic agents(e.g.,acetylcysteine, potassium iodide) because they may worsen cough or airflow obstruction.

130. •Sedation is not generally recommended .
• Anxiolytic and hypnotic drugs are contraindicated in severely ill asthma patients because of their respiratory depressant effect.

131. Emergency Department and Hospital Management of Acute Asthma in Adults
Management Protocol

132. First-line Drugs Oxygen to keep SaO2 > 92% Inhaled β2 Agonists: Salbutamol (Albuterol)
1. MDI: 4-8 puffs (100 μg/puff) q15-20 min with spacer
2. Wet Nebulizer: 2.5-5 mg (0.5-1 ml) in 2.5- 3 ml normal saline q15-20 min Corticosteroids
• Oral: prednisone 40-60 mg
• Intravenous: parenteral hydrocortisone, 100 mg q6h

133. Initial Assessment of Acute Asthma

134. Initial Management of Acute Asthma

135. If there is an adequate response

136. If there is a partial response

137. If there is a poor response

138. Noninvasive positive-pressure ventilation may benefit carefully selected patients
•In acute severe asthma, continuous positive airway pressure decreases the work of breathing, causes bronchodilatation, decreases airway resistance, reexpands atelectatic lung, promotes removal of secretions, relaxes the diaphragm and inspiratory muscles, decreases the adverse hemodynamic effects of large negative-peak and -mean inspiratory pleural pressures, and may offset intrinsic positive end-expiratory pressure (PEEP).

139. •NPPV can be safely used in a patient with severe asthma and hypercapnia whose condition has not improved despite aggressive medical management.
• NPPV should be tried before intubation in alert, cooperative patients who have not improved with aggressive medical therapy.
•However, NPPV should not be attempted in patients who are rapidly deteriorating or in those who are somnolent or confused.

140. •Furthermore, NPPV should be avoided in patients who are hypotensive (systolic blood pressure less than 90 mm Hg), have myocardial ischemia or significant ventricular dysrhythmias, are unable to protect their airway, or have life-threatening hypoxemia (oxygen saturation less than 90% or PaO2 less than 60 mm Hg on a rebreathing face mask).

141. •BiPAP may also decrease the need for intubation and ICU care in adults with status asthmaticus, although the literature is not conclusive
•BiPAP is not a substitute for endotracheal intubation and mechanical ventilation

142. •The decision to intubate an asthmatic patient is difficult and should never be made lightly.
•The timing of intubation is essentially based on clinical judgment.
•Although hypercapnia (PaCO2 greater than 40 mm Hg) is a worrisome finding in patients with acute asthma, after evaluation, most of these patients will not require intubation.
•A high PaCO2 alone is not an indication for intubation if the patient is alert and cooperative

143. Indications for intubation and mechanical ventilation in near-fatal asthma
Refractory hypoxemia (PaO2 <60mmHg) Persistent hypercapnia (PaCO2 >55–77mmHg) Increasing hypercapnia (PaCO2 >5mmHg/h) Signs of exhaustion despite bronchodilator therapy Worsening of mental status Hemodynamic instability Coma or apnea

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145. Ann Thorac Med 2009; 4(4): 216-233

146. Work hard in silence
Let success make the noise
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