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Acute

exacerbation of
asthma in adult
.

August 2015

Asthma cigarettes in 1800s


an anti-muscarinic alkaloid
N Engl J Med 2012; 366:827-834

Asthma Acute asthmatic


attack

Asthma

Definition : GINA updated 2012

A chronic inflammatory disorder of the


airways in which many cells and cellular elements
play a role.
The chronic inflammation is associated with
airway hyperresponsiveness that
leads to recurrent episodes of wheezing,

breathlessness, chest tightness,


and coughing, particularly at night or in the

early morning.
These episodes are usually associated with
widespread, but variable, airflow

GINA 2015
Asthma is a heterogeneous disease, usually
characterized by chronic airway
inflammation. It is defined by the history of
respiratory symptoms such as wheeze,
shortness of breath, chest tightness
and cough that vary over time and in
intensity, together with variable
expiratory airflow limitation.
Asthma is usually associated with airway
hyperresponsiveness to direct or indirect stimuli, and
with chronic airway inflammation

Asthma Pathophysiology
On-and-Off
Symptoms
Variable airflow limitation
Bronchial hyperresponsive

Inflammation

What can be easily measured clinically

Acute asthmatic attack


(Exacerbation of asthma)
Episodes of progressive
increase in shortness of
breath, cough, wheezing
or chest tightness + decrease
GINA 2015
in lung function
Airflow limitation, measured by
PEF or FEV1, is a more reliable
severity index than symptoms

Exacerbation can also occurred


in
patients
with
well-controlled
PEF (L/min)
asthma
Exacerbation

AM

PM

AM

PM

AM

PM

AM

PM

AM

PM

AM

PM

PEF (L/min)

Exacerbation

AM

PM

AM

PM

AM

PM

AM

PM

Asthma management GINA 2015


Chapter 3 : Treating asthma to control
symptoms and minimize risk
Part A General principles
Part B Medication and strategies
Part C Guided asthma self-Mx
Part D Mx asthma with comorbid/
special pop
Chapter 4 : Management of worsening
asthma and exacerbations

GINA 2015

Add tiotropium

Acute asthmatic
attack

Spasm
Swelling
Secretion

http://www.nhlbi.nih.gov/health/health-topics/topics/asthma/

Pathophysiology of
asthmatic
acute asthmaEarly
attack :
Airway obstruction

Hypoxemia (V/Q
Uneven
distribution of
mismatch)

Hyperinflation

Increased wasted
Ventilation

ventilation
Increased work of breathing

V/Q mismatch

Increase O2 consumption and CO2 production


Respi muscle
fatigue

Hypoxemia and hypercarbia

Respiratory acidosis and metabolic acidosis

Late :
Hypercarbia /
Ventilatory
failure

Mx of asthma
exacerbation

Mx of acute asthmatic attack


(Ddx and) evaluation of
severity
Supportive Rx
O2 supplement
Bronchodilator
Ventilatory support (ETT)
Other adjunctive Rx
Specific Rx
Steroid
(Bronchodilator)
Re-evaluate clinical
response

Mx of acute asthmatic attack


(Ddx and) evaluation of
severity
Supportive Rx
O2 supplement
Bronchodilator
Ventilatory support (ETT)
Other adjunctive Rx
Specific Rx
Steroid
(Bronchodilator)
Re-evaluate clinical
response

Differential diagnosis
Is it asthma?
Asthma mimicker
COPD exacerbation
Congestive heart failure
Anaphylaxis
Foreign body obstruction
Not all wheezing is asthma!
Vocal cord dysfunction

Is it Asthma?
History
Age : Onset at young age (Some
exception Late onset asthma)
History of allergy : Allergic rhinitis,
Sinusitis, Allergic dermatitis
Hx of aggravating factors : Cold air, Dust
mites, Smokes / air pollution
Family history of asthma

Physical examination

Is it Asthma?
History
Physical examination
Signs of allergic rhinitis :
Allergic shiner, Nasal crease
No obvious sign of chronic airtrapping (EXCEPT in uncontrolled
long standing asthma)

Lab

Is it Asthma?
History
Physical examination
Lab
PEF variation
Spirometry : bronchodilator
response
Bronchial hyperresponsive test

Asthma VS COPD Why bother?


Some similar managements
Bronchodilators
Systemic glucocorticoids
ATB in eligible cases

BUT !!!

Asthma VS COPD Why bother?


ASTHMA

Younger age , fully recoverable


BUT can also be MORTAL if suboptimal treated
More rapid change : Flip-flop of
symptoms
Monitoring of PEF is mandatory!!
NIV is not recommended
Asthma patients requiring MV
should be intubated

ACOS Asthma and COPD


Overlap Syndrome
For acute
exacerbation :
Likely to be
more safe if treat
as asthma
NIV ?

Evaluation of severity
History (Indicate more
severe disease)
Hx previous intubation
Hx admission from asthma
within 1 year
Use of B2 agonist > 1
canister / mo
Current steroid use

GINA 2015 factors those


increase asthma-related death
A history of near-fatal asthma requiring ETT + MV
Hospitalization or ER visit for asthma in the past
year
Currently using / recently stopped oral
corticosteroids
Not currently using inhaled corticosteroids
Over-use of SABAs (>1 canister of salbutamol/mo)
A history of psychiatric dis or psychosocial problems
Poor adherence with medications / action plan
Food allergy in a patient with asthma

UpToDate accessed 11 Jul 2015

History of high risk of


NFA

High risk for near fatal asthma when compared to hospitalized


controlled patients
Turner MT. AJRCCM 1998;157:1804-9

Meta-analysis
Patients with history of
mechanical ventilation
use
increase risk of nearfatal asthma
OR 4.738 [2.49-9.03]

GG Alvarez, et al. Can Respir J 2005; 12(5):265-70

Evaluation of severity (2)

Physical
Signsexam
of impending
respiratory failure
Unable to supine
Incomplete
sentences
Accessory muscle
use
Abdominal
paradox

More severe /
respiratory
failure
Unconscious
Air-hunger
RR < 12 /
min
BP drop

Immediat
e
Intubatio
n!

Signs of severe
exacerbation

GINA 2015

Evaluation of severity (3)


Laboratory
PEF**
(< 200 Liter/min = Severe)
ABG (Optional)
CXR
To find the cause in severe case
UpToDate accessed 11 Jul 2015 e.g. pneumonia

Reported
dyspnea
score

40% of patients
PEF

60% of patients

Perception of dyspnea
is generally poor
Kendrick AH. BMJ. 1993 Aug 14;307(6901):422-4.

CHEST 2002; 121:329333

Pts with
poor
perception
visit ER
more
frequent!

POD = Perception of dyspnea

Measured by breathing against


a resistance device and report sensation
as Borg scale, then compared to
100 normal subjects

Predicted PEF
ATS scale

Use predicted value supplied by the manufacturer

EU scale

ABG: who is needed to be tested ?


hypercapnia
ABG is not warranted for Usually
all case
in asthma occurs only
**Availability of oximetry when PEF < 25%
(100-150 LPM)

UpToDate
accessed 11 Jul
2015

Indication To evaluate pCO2 and


pH
Patients with FEV1 <40% predicted
(indicated)

Chest radiography

Routine chest
radiography is not
required
Performed if Findley
failure
to 1981; 80:535LJ. Chest
response
Unrecognized
pneumothoraxGershel JC. N Engl J Med 1983; 309: 336pneumomediastinum
Severe airflow
obstruction required

Treatment of acute severe asthma

Goal of treatment
1 Correction of arterial hypoxemia
2 Reversal of airflow obstruction
with minimal side effect

Mx of acute asthmatic attack


(Ddx and) evaluation of
severity
Supportive Rx
O2 supplement
Bronchodilator
Ventilatory support (ETT)
Other adjunctive Rx
Specific Rx
Steroid
(Bronchodilator)
Re-evaluate clinical
response

Supportive Rx
Oxygen supplement
Bronchodilator
Ventilatory support
Other adjunctive Rx

Oxygen supplement
Keep Sat O2
just 90% (up
to 95%)
Low-flow O2
and titrate
against pulse
oximeter

Rodrigo GJ, et al. Chest 2003; 124:13121317.


Moloney E, et al. Chest 2002; 121:18061811.
GINA 2015

Caution of O2 in acute asthma

Rodrigo GJ et al. Chest 2003; 124:1312


1317

Perrin K. Thorax. 2011


Nov;66(11):937-41.

Bronchodilator



(parenteral or
inhaled?)

MDI spacer small volume
nebulizer
continuous intermittent
nebulization

Parenteral and inhaled


bronchodilator

Terbutaline SC, IM or IV

Salbutamol NB

Nebulized
bronchodilator

Aerosolized 2 agonist : at least equal to


William SJ. Comparison of inhaled and intravenous turbutaline in acute severe asth
and often superior
to parenteral therapy
Thorax 1988; 43: 19023
Cheong B. Intravenous beta-agonist in acute severe asthma. BMJ 1988;297:488-50
Aerosolized form of 2 agonist are first
choice
No evidence to support the routine use of IV
beta2-agonists in patients with severe asthma
exacerbation

Terbutaline 0.25 mg SC q 20 minutes up to 3 doses (Rare


response reported)

Theophylline /
Aminophylline

Not effective in acute asthma


Methylxanthines appear to
increase the incidence of
adverse effects
Add on therapy to SABA not
UpToDate accessed 11 Jul 2015
GINA 2015
helpful



(parenteral or
inhaled? )

MDI spacer small volume
nebulizer
continuous intermittent
nebulization

Type of inhaled bronchodilator


Short acting Beta-2 agonist
(SABA)
Short acting anticholinergic
(Anti-muscarinic)
(SAMA)
Beta-2 agonist anticholinergic
combination

Beta-2 agonist
5 mg / mL

100 mcg / puff

Salbutamol (Ventolin)

Usual dose of
Beta2 agonist

MDI : Salbutamol 2.4 mg (2400 g) per


hr
4 puff q 10 min interval by MDI with
spacer
NB : Salbutamol (2.5 mg) NB every 20
min
Salbutamol 0.5 mL (to 1 mL) + NSS to 3
mL
[ dose NB

Anticholinergic
Increased vagal tone in
asthmatic airway
Role of anticholinergic is less well
defined (than B2A)

Beta-2 agonist
anticholinergic
combination

Berodual Forte (unit dose vial)


Berodual solution
Fenoterol 1.25 mg + IB 0.5 mg /vial Fenoterol 0.5 mg + IB 0.25 mg /mL

Berodual (Fenoterol and Ipratropium


bromide)

Adding IB to SABA
in mod-severe asthma

Rodrigo GJ. Thorax. 2005 Sep;60(9):740-6.

Decrease
hospitalization
Improvement of FEV1
Compare to SABA
alone

When to use combined


B2A and Anticholinergic
Not respond to 3rd dose of
SABA alone

Thai asthma CPG 2012

Usual dose of combined


B2A and Anticholinergic
Berodual solution : 1 mL + NSS 3
mL NB (1:3)
[up to 2 4 mL in severe case]
(0.5 mg of IB NB q 20 min x 3 doses at
ER)
Usually discontinued during
admission
UpToDate accessed 11 Jul 2015



(parenteral or
inhaled? )

MDI spacer small volume
nebulizer
continuous intermittent
nebulization

pMDI with spacer versus NB

Volumetric
spacer

Handheld (Small volume)


Nebulizer

MDI bronchodilator
Equally effective delivery of aerosolized
medication or MDI
(with spacer)
MDI therapy is at least effective as nebulized form
Turner M. Arch Intern Med 1997:
158:1736-44.

Less evidence in severe and near-fatal cases


Most physician [and some patients] accustomed
to use nebulized medication for treatment acute
severe asthma

MDI bronchodilator

4 puff (2-6 puff) of MDI q 20 min


Cheaper cost (The differences in
cost between MDI and nebulizer)
Turner MO. A review and economic evaluation of bronchodilator delivery methods in
hospitalized patients. Arch Intern Med 1996;156:2113-8



(parenteral or
inhaled? )

MDI spacer small volume
nebulizer
continuous intermittent
nebulization

Continuous
nebulization
Frequent refill of normal nebulizer
Nebulizer with infusion pump
Large-volume nebulizer with high-output
extended aerosol respiratory therapy

Continuous versus intermittent NB

Meta-analysis of RCT of adult with


acute severe asthma
No significant difference
in
PFT
(FEV1)
Rodrigo GJ, Rodrigo C. Chest 2002;
122:160165.
and hospitalization rate

In cases with worse lung function


Reduced hospitalizations, better
lung function with continuous
compared with intermittent
nebulization

Camargo CA. Cochrane Database Syst Rev 2003.

Ventilatory support
Ventilatory failure (Late consequence)
from respiratory muscle fatigue
ETT is recommended
Non-invasive ventilator (CPAP, BiPAP) is
risky due to the flip-flop nature of asthma
(Pt can get worse all of a sudden)
NIV may be considered case-by-case by
an expert under close monitoring!

BiPAP improves
outcome
BiPAP use in
asthma:
Improve lung function
Reduce the need for
hospitalization
CHEST 2003; 123:10181025

IV trial
N
r
o
f
ded
e
e
n
s
i
toring
i
n
o
m
lose
c
/
e
v
i
Intens

Adjunctive therapy
Inhaled corticosteroid
Magnesium
Adrenaline

Intravenous magnesium sulfate


Mechanism : inhibit smooth
muscle cell calcium channel
and muscle contraction

Spivey WH, Skobeloff EM, Levin RM. Effect of magnesium chloride


on rabbit bronchial smooth muscle. Ann Emerg Med 1990;
19:11071112

Intravenous magnesium sulfate


Meta-analysis : not support
routine use
Silverman RA et al. Chest 2002;
122:48997
Rodrigo G. Am J Emerg Med 2000;
18:216221
Koepsell T. Ann Emerg Med 1999;
36:191197

May be used in severe cases


Reduces hospital admissions
in some patients

2 g IV drip in 20 min

Adults with FEV1 <2530%


Adults and children who fail to
respond
Children whose FEV1 fails to
reach 60% after 1 h of Rx

GINA
2015

Mx of acute asthmatic attack


(Ddx and) evaluation of
severity
Supportive Rx
O2 supplement
Bronchodilator
Ventilatory support (ETT)
Other adjunctive Rx
Specific Rx
Steroid
(Bronchodilator)
Re-evaluate clinical
response

Specific Rx
Systemic corticosteroid *****
Reduce admission and relapse
rate
IV or Oral corticosteroids
IV dexamethasone
4-10 mg IV q 6h
Oral prednisolone
50 mg/day

Systemic corticosteroid
Early corticosteroid administration
Within 1 hour of presentation to the ER

prevent hospitalization

Rower BH, et al. Early


Emergency Department
Treatment of Acute
Asthma with Systemic
Corticosteroid.
Cochrane Database of
Systematic Reviews
2001

Systemic corticosteroid
administration prevent
relapse, NNT = 10

Effects up to 3 weeks

Rowe BH, et al. Cochrane Database


Syst Rev. 2007 Jul 18;(3):CD000195.

Corticosteroid
Systemic corticosteroid should be considered in
management of almost all asthma exacerbation
ESPECIALLY
Initial SABA fails to achieve lasting improvement
Patient taking oral corticosteroid (OCS)
A history of previous exacerbations requiring
OCS
Oral and IV corticosteroid are equivalent
GINA 2015

Systemic
corticosteroid
Duration of systemic corticosteroid
Thai asthma CPG 2012

5 days of corticosteroid may be equally effective


(No difference of morning PEF compare to 10 days of
steroid)
Jones AM, et al. Respir Med 2002; 96:950954
GINA 2015

Systemic and inhaled CS


Variable

Systemic
corticosteroid

Inhaled corticosteroid

Effect

Systemic anti-inflammation

Topical

Time delay

Late improvement in
outcome (>6 h)

Early improvement in
outcome

Mechanism

Corticosteroid induce
transcriptional effect :
synthesis new protein

Corticosteroid up-regulate
receptor
Mucosal vasoconstriction
Decongestion

Acun a AA, et al. Eur Respir J 2002; 19:872878


Fe lez MA et al.. Am J Respir Crit Care Med 1994; 150:369373
Rodrigo G, Rodrigo C. Inhaled flunisolide for acute severe asthma. Am J Respir Crit Care Med 1998;
157:698703

Role of ICS in acute asthma


A meta-analysis concluded that inhaled
CCS compared with placebo reduced
hospital admission rates in patients with
acute asthma
However it is unclear if there is a benefit
of ICS when used in comparison or in
addition to systemic corticosteroids
Edmonds ML et al. Cochrane Database Syst Rev. 2012 Dec
12;12:CD002308.

Role of ICS (GINA 2014)

High dose: 12 puff of budesonide / day


Higher cost

Role of ICS in acute asthma


A therapeutic benefit from addition
of ICS to Rapid onset bronchodilator
is demonstrated in patients with
most severe asthma
Rodrigo GJ, Rodrigo C. Triple inhaled drug
protocol for the treatment of acute severe
asthma.
Chest 2003; 123:19081915

In summary : Systemic steroid is a


mainstay,
ICS may be added in selected cases

Core treatments of acute asthma


Agents

Administration

Oxygen

High flow to maintain SaO2 >92-95%


(via nasal prong, mask, ET)

2-agonist

MDI: Initial dose 4-8 puffs (salbutamol 100g /p) can be


repeated q 15-20 min up to 3 times
Wet NB: Initial dose 5-10 mg of salbutamol
repeated q 15-20 min
For severe attack NB can run continuously

Corticosteroid

Prednisolone 50 mg orally or methylprednisolone 125 mg IV

Summary of dosages

Agents

Administration

Anticholinergic

MDI dose 4-8 puff (20 mcg/puff) q 15-20 min to be


repeated 3 times
Increase dose to 1 puff q -1 min to max 20 puff
NB dose: initial 0.25-0.5 mg (1 ml in 3 ml saline) q
15-20 min or continuous

Magnesium sulfate

Intravenous infusion 25 mg/kg/hr [1 Vial = 1g]


(Up to 2 g IV drip in 20 min)
Dose 0.3-0.5 ml (1:1000) (SC) q 15-20 min

Adrenaline
Intravenous 2 agonist

Salbutamol 4 g/kg over 2-5 min and then infusion


0.1-0.2 g/kg/min

Aminophylline

Loading 3-6 mg/kg iv over 30 min


(To be halved in patients already on theophylline)

Summary of dosages

Mx of acute asthmatic attack


(Ddx and) evaluation of
severity
Supportive Rx
O2 supplement
Bronchodilator
Ventilatory support (ETT)
Other adjunctive Rx
Specific Rx
Steroid
(Bronchodilator)
Re-evaluate clinical
response

Re-evaluate clinical response


Acute asthma
Evaluation
Bronchodilator (SABA +/- SAMA)
Systemic corticosteroid is administrated in
patients whose severity factors are identified

Re-evaluation & PEFR


Discharge

Admit

PEF General concepts


OPD - Controlled asthma
PEF 80% predicted

ER - Patients with acute attack


stable enough to D/C home
PEF 70 (60)% predicted
No wheezing and acceptable HR
& RR

What to be
considered

Clinical status (including the


ability to lie flat) and lung
function 1 hour after Rx
More reliable predictors of the
need for hospitalization than
the patients status on arrival
GINA 2015

GINA 2015

When to discharge

GINA 2015

Ramathibodi CPG

Conditions to be considered

Unconscious
Air hunger
RR< 12/min
Unstable
hemodynamic

Hx of
intubation
Hx of steroid
(ICS, oral)
Admission in 1
y
Salbutamol >1
History
canister/month
PR > 130
RR > 30
Wheezing

+
PEF

Emergency Intubation

Incomplete
sentence
Accessory
muscle use
Abdominal
paradox
Unable to lie
Physical exam
down

Severity Steroid

Incomplete
Continue treatment
resolution

Acute asthma
A

Unconscious
Air hunger
RR< 12/min
Unstable
hemodynamic

B
Hx of intubation
Hx of steroid
(ICS, oral)
Admission in 1 y
Salbutamol >1
canister/month

Assessment 1

Intubation

Initial PEFR

Assessment 2

PR > 130
RR > 30
Wheezing

1st MDI w/ spacer


Plus steroid if any B,D

PEF

Incomplete
sentence
Accessory
muscle use
Abdominal
paradox
Unable to lie
down

1st MDI spacer


A

Plus steroid if any of B,D


Unconscious
Air hunger
RR< 12/min
Unstable
hemodynamic

PR > 130
RR > 30
Wheezing

Assessment 3
A+C+D+PEF

2nd, 3rd MDI w/ spacer as needed

PEF

Incomplete
sentence
Accessory
muscle use
Abdominal
paradox
Unable to lie
down

(15-20 min with interval assessment)

Assessment 4
PEF>70%

PEF>70%
+any C

PEF 50-70%
+any of C

A+C+D+PEF
PEF 50-70
+any A,D

PEF <50%

Unconscious
Air hunger
RR< 12/min
Unstable
hemodynamic

PR > 130
RR > 30
Wheezin
g

Assessment 4
PEF>70%

PEF>70%
+any C

PEF 50-70%
+any of C

Incomplete sentence
Accessory muscle
use
Abdominal paradox
Unable to lie down

PEF

A+C+D+PEF
PEF 50-70
+any A,D

PEF <50%

4th MDI w/ spacer


PEF>70%

Discharge

PEF 50-70%
+any of C

Admit ward

Admit ICU (IMU)

Clinical record form

Initial PEF

Clinical record form

After D/C
Follow-up at OPD


Within 5-7 days after D/C

Re-evaluate controller drugs

Step-up therapy usually needed


Previously well-controlled patients
with just one episode of attack (with
known precipitated cause) may be OK
to continue the previous controller

Asthma
reading

Further

Thai asthma
guidelines (2555)

Thank you
for your attention