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hwernhwern
Status Asthmaticus in ChildrenStatus Asthmaticus in Children
Heinrich WernerHeinrich Werner
Pediatric Critical CarePediatric Critical Care
University of Kentucky ChildrensUniversity of Kentucky ChildrensHospitalHospital
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Status asthmaticusStatus asthmaticus
ObjectivesObjectives
The participant will increase his/herThe participant will increase his/her
Awareness of rising morbidity/mortality of severe asthma inAwareness of rising morbidity/mortality of severe asthma in
childrenchildren
Ability to define who is at risk for dyingAbility to define who is at risk for dying
Understanding of the pathologic, metabolic and biomechanicalUnderstanding of the pathologic, metabolic and biomechanical
eventsevents
Ability to predict respiratory failure and to determine theAbility to predict respiratory failure and to determine the
need for early transferneed for early transfer
Ability to tailor the therapeutic regimen according to severityAbility to tailor the therapeutic regimen according to severity
and progression of status asthmaticusand progression of status asthmaticus
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Status asthmaticusStatus asthmaticus
Status Asthmaticus in ChildrenStatus Asthmaticus in Children
EpidemiologyEpidemiology
PathophysiologyPathophysiology
Presentation and AssessmentPresentation and AssessmentTreatmentTreatment
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Status asthmaticusStatus asthmaticus
Status Asthmaticus in ChildrenStatus Asthmaticus in Children
EpidemiologyEpidemiology
PrevalencePrevalence
MorbidityMorbidity
MortalityMortalityRisk factorsRisk factors
PathophysiologyPathophysiology
Presentation and assessmentPresentation and assessment
TreatmentTreatment
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Status asthmaticusStatus asthmaticus
PrevalencePrevalence
The prevalence of pediatric asthma in theThe prevalence of pediatric asthma in theUS is increasingUS is increasing
0
10
20
30
40
50
60
0-4 yrs 5-14 yrs 15-34 yrs
1975
1980-81
1985
1989
1990-92
1993-95
Rate of self-reported asthma/1,000 populationRate of self-reported asthma/1,000 population
Mannino DM. MMWR 1998;47(1):1-27Mannino DM. MMWR 1998;47(1):1-27
: Epidemiology: Epidemiology
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Status asthmaticusStatus asthmaticus
MorbidityMorbidity
0
10
20
30
40
50
60
70
1
980
1
982
1
984
1
986
1
988
1
990
1
992
Rateper10,0
00
population
1 year
1-4 years
5-14 years
15-24 years
!ospital dis"har#e rates for asthma!ospital dis"har#e rates for asthma
MMWR 1996;45(17):350-3MMWR 1996;45(17):350-3
The morbidity of pediatric asthma in theThe morbidity of pediatric asthma in the
US is increasingUS is increasing
: Epidemiology: Epidemiology
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Status asthmaticusStatus asthmaticus
MortalityMortality
0
1
2
3
4
5
6
7
1979-80 1981-83 1984-86 1987-89 1990-92 1993-95
Rateper1,0
00,0
00
population
0-4 years5-14 years
15-34 years
The mortality of pediatric asthma in the USThe mortality of pediatric asthma in the US
is increasingis increasing
Rates of death in "hildren from asthmaRates of death in "hildren from asthma
Mannino. MMWR 1998;47(1):1-27Mannino. MMWR 1998;47(1):1-27
: Epidemiology: Epidemiology
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Status asthmaticusStatus asthmaticus
Risk factors for fatal asthmaRisk factors for fatal asthma
MedicalMedicalPrevious attack with rapid/severe deterioration or respiratoryPrevious attack with rapid/severe deterioration or respiratory
failure or seizure/loss of consciousnessfailure or seizure/loss of consciousness
PsychosocialPsychosocial
Denial, non-complianceDenial, non-compliance
Depression or other psychiatric disorderDepression or other psychiatric disorder
Dysfunctional familyDysfunctional family
Inner city residentInner city resident
EthnicEthnic
Non-white childNon-white child
: Epidemiology: Epidemiology
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Status asthmaticusStatus asthmaticus
Status Asthmaticus in ChildrenStatus Asthmaticus in Children
EpidemiologyEpidemiology
PathophysiologyPathophysiology
CytokinesCytokines
Airway pathologyAirway pathology
Autonomic nervous systemAutonomic nervous system
Pulmonary mechanicsPulmonary mechanics
Cardiopulmonary interactionsCardiopulmonary interactions
MetabolismMetabolism
Presentation and assessmentPresentation and assessmentTreatmentTreatment
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Status asthmaticusStatus asthmaticus
PathophysiologyPathophysiology
Asthma is primarily an inflammatory diseaseAsthma is primarily an inflammatory disease
$u"ous plu##in#$u"ous plu##in#
%mooth mus"le%mooth mus"le
spasmspasm &ir'ay edema&ir'ay edema
: Pathophysiology: Pathophysiology
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Status asthmaticusStatus asthmaticus
Inflammatory cytokinesInflammatory cytokines
Activated mast cells and lymphocytesActivated mast cells and lymphocytes
produce pro-inflammatory cytokinesproduce pro-inflammatory cytokines
(histamine, leukotrienes, PAF), which are(histamine, leukotrienes, PAF), which are
increased in asthmatics airways andincreased in asthmatics airways and
bloodstreambloodstream
: Pathophysiology: Pathophysiology
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Status asthmaticusStatus asthmaticus
Irritable and damaged airwayIrritable and damaged airway
HypersecretionHypersecretion
Epithelial damage with
exposed nerve endings
Epithelial damage with
exposed nerve endings
Hypertrophy of goblet cells
and mucus glands
Hypertrophy of goblet cells
and mucus glands
: Pathophysiology: Pathophysiology
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Status asthmaticusStatus asthmaticus
AirwayAirway
The irritable and inflamed airway is susceptible toThe irritable and inflamed airway is susceptible toobstruction triggered byobstruction triggered by
AllergensAllergens
InfectionsInfections
Irritants including smokeIrritants including smoke
ExerciseExercise
Emotional stressEmotional stress
GE refluxGE reflux
DrugsDrugs
Other factorsOther factors
: Pathophysiology: Pathophysiology
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Status asthmaticusStatus asthmaticus
Autonomic nervous systemAutonomic nervous system
Bronchodilation Bronchoconstriction
SympatheticSympathetic Circulating catecholaminesCirculating catecholaminesstimulate -receptorsstimulate -receptors
--
ParasympatheticParasympathetic Vagal signals stimulateVagal signals stimulatebronchodilating Mbronchodilating M22 --receptorsreceptors
Vagal signals stimulateVagal signals stimulatebronchoconstricting Mbronchoconstricting M33--
receptorsreceptors
Nonadrenergic-Nonadrenergic-
noncholinergicnoncholinergic
(NANC)(NANC)
Release of bronchodilatingRelease of bronchodilating
neurotransmitters (VIP, NO)neurotransmitters (VIP, NO)
Release of tachykinins (substanceRelease of tachykinins (substance
P, neurokinin A)P, neurokinin A)
: Pathophysiology: Pathophysiology
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Status asthmaticusStatus asthmaticus
Lung mechanicsLung mechanics
HyperinflationHyperinflation
Obstructed small airways cause prematureObstructed small airways cause premature
airway closure, leading to air trapping andairway closure, leading to air trapping and
hyperinflationhyperinflation
HypoxemiaHypoxemia
Inhomogeneous distribution of affected areasInhomogeneous distribution of affected areas
results in V/Q mismatch, mostly shuntresults in V/Q mismatch, mostly shunt
: Pathophysiology: Pathophysiology
S h i iP th h i l
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Status asthmaticusStatus asthmaticus
Severe airflowSevere airflow
obstructionobstruction
IncompleteIncomplete
exhalationexhalation
Increased lungIncreased lung
volumevolume
Increased elasticIncreased elastic
recoil pressurerecoil pressure
IncreasedIncreasedexpiratory flowexpiratory flow
Expanded smallExpanded small
airwaysairways
Decreased expiratoryDecreased expiratoryresistanceresistance
Compensated:Compensated:
Hyperinflation, normocapniaHyperinflation, normocapnia
Decreased expiratoryDecreased expiratoryresistanceresistance
Decompensated:Decompensated:
Severe hyperinflation, hypercapniaSevere hyperinflation, hypercapnia
WorseningWorsening
airflowairflow
obstructionobstructionFrom text in :From text in :
Tuxen. Am RevTuxen. Am Rev
Respir DisRespir Dis
1992;146:11361992;146:1136
: Pathophysiology: Pathophysiology
St t th tiSt t th ti P th h i lP th h i l
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Status asthmaticusStatus asthmaticus
Cardiopulmonary interactionsCardiopulmonary interactions
Left ventricular loadLeft ventricular load
Spontaneously breathing children with severeSpontaneously breathing children with severe
asthma have negative intrapleural pressureasthma have negative intrapleural pressure
(as low as -35 cmH(as low as -35 cmH22O) during almost theO) during almost theentire respiratory cycleentire respiratory cycle
Stalcup S. N Engl J Med 1977;297:592-6Stalcup S. N Engl J Med 1977;297:592-6
Negative intrapleural pressure causesNegative intrapleural pressure causes
increased left ventricular afterload, resultingincreased left ventricular afterload, resultingin risk for pulmonary edemain risk for pulmonary edema
Buda AJ. N Engl J Med 1979;301(9):453-9Buda AJ. N Engl J Med 1979;301(9):453-9
: Pathophysiology: Pathophysiology
St t th tiSt t th ti P th h i lP th h i l
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Status asthmaticusStatus asthmaticus
Cardiopulmonary interactionsCardiopulmonary interactions
Right ventricular loadRight ventricular load
Hypoxic pulmonary vasoconstriction and lungHypoxic pulmonary vasoconstriction and lung
hyperinflation lead to increased righthyperinflation lead to increased right
ventricular afterloadventricular afterloadDawson CA. J Appl Physiol 1979;47(3):532-6Dawson CA. J Appl Physiol 1979;47(3):532-6
: Pathophysiology: Pathophysiology
St t th tiStatus asthmaticus Pathoph siolog: Pathophysiology
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Status asthmaticusStatus asthmaticus
Cardiopulmonary interactionsCardiopulmonary interactions
Pulsus paradoxusPulsus paradoxus
P. paradoxus is the clinical correlate of cardiopulmonaryP. paradoxus is the clinical correlate of cardiopulmonary
interaction during asthma. It is defined as exaggeration ofinteraction during asthma. It is defined as exaggeration of
the normal inspiratory drop in systolic BP : normally < 5the normal inspiratory drop in systolic BP : normally < 5
mmHg, but > 10 mmHg in pulsus paradoxus.mmHg, but > 10 mmHg in pulsus paradoxus.
()pir()pir *nspir
NlNl
P. paradoxP. paradox
*nspir()pir()pir
: Pathophysiology: Pathophysiology
Status asthmaticusStatus asthmaticus : Pathophysiology: Pathophysiology
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Status asthmaticusStatus asthmaticus
Pulsus paradoxus correlates withPulsus paradoxus correlates with
severityseverity
All patients who presented with FEVAll patients who presented with FEV11of < 20%of < 20%
(of their best FEV(of their best FEV11 while well) had pulsuswhile well) had pulsus
paradoxusparadoxus
Pierson RN. J Appl Physiol 1972;32(3):391-6Pierson RN. J Appl Physiol 1972;32(3):391-6
: Pathophysiology: Pathophysiology
Status asthmaticusStatus asthmaticus : Pathophysiology: Pathophysiology
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Status asthmaticusStatus asthmaticus
Cardiopulmonary interactionsCardiopulmonary interactions
+e#atie intrapleural+e#atie intrapleural
pressurepressure
ulmonary edemaulmonary edema ulsus parado)usulsus parado)us
!yperinflation!yperinflation
!ypotension!ypotension
<ered hemodynami"s<ered hemodynami"s
: Pathophysiology: Pathophysiology
Status asthmaticusStatus asthmaticus : Pathophysiology: Pathophysiology
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Status asthmaticusStatus asthmaticus
MetabolismMetabolism
./ mismat"h./ mismat"h
!ypo)ia!ypo)ia
ehydrationehydration
a"tatea"tate etonesetones
$etaoli" a"idosis$etaoli" a"idosis
*n"reased 'or*n"reased 'or
of reathin#of reathin#
: Pathophysiology: Pathophysiology
Status asthmaticusStatus asthmaticus
: Presentation: Presentation
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Status asthmaticusStatus asthmaticus
PresentationPresentation
CoughCough
WheezingWheezing
Increased work of breathingIncreased work of breathing
AnxietyAnxiety
RestlessnessRestlessness
Oxygen desaturationOxygen desaturation
Audible wheezes : reasonable airflowAudible wheezes : reasonable airflowAudible wheezes : reasonable airflowAudible wheezes : reasonable airflow
Silent chest : ominous!Silent chest : ominous!Silent chest : ominous!Silent chest : ominous!
: Presentation: Presentation
Status asthmaticusStatus asthmaticus : Assessment: Assessment
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Status asthmaticusStatus asthmaticus
AssessmentAssessment
Findings consistent with impending respiratoryFindings consistent with impending respiratory
failure:failure:
Altered level of consciousnessAltered level of consciousness
Inability to speakInability to speak Absent breath soundsAbsent breath sounds
Central cyanosisCentral cyanosis
DiaphoresisDiaphoresis
Inability to lie downInability to lie down Marked pulsus paradoxusMarked pulsus paradoxus
: Assessment: Assessment
Status asthmaticusStatus asthmaticus : Assessment: Assessment
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Status asthmaticusStatus asthmaticus
Clinical Asthma ScoreClinical Asthma Score
00 11 22Cyanosis orCyanosis or NoneNone In airIn air In 40%In 40%
PaOPaO22 >70 in air>70 in air < 70 in air< 70 in air < 70 in 40%< 70 in 40%
Inspiratory B/SInspiratory B/S NlNl Unequal orUnequal or AbsentAbsent decreaseddecreased
Expir wheezingExpir wheezing NoneNone ModerateModerate MarkedMarked
Cerebral functionCerebral function NlNl DepressedDepressed ComaComa
AgitatedAgitated
Wood DW. Am J Dis Child 1972;123(3):227-8Wood DW. Am J Dis Child 1972;123(3):227-8
5 impendin# resp failure5 impendin# resp failure: Assessment: Assessment
Status asthmaticusStatus asthmaticus : Assessment: Assessment
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Status asthmaticus
Chest X-RayChest X-Ray
Not routinely indicatedNot routinely indicated
Exceptions:Exceptions: Patient is intubated/ventilatedPatient is intubated/ventilated
Suspected barotraumaSuspected barotrauma
Suspected pneumoniaSuspected pneumonia
Other causes for wheezing are being suspectedOther causes for wheezing are being suspected
: ssess e t
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ABGABG
Early status asthmaticus: hypoxemia,Early status asthmaticus: hypoxemia,
hypocarbiahypocarbia
Late: hypercarbiaLate: hypercarbia
Decision to intubate should not depend onDecision to intubate should not depend onABG, but on clinical assessmentABG, but on clinical assessment
Frequent ABGs are crucial in the ventilatedFrequent ABGs are crucial in the ventilated
asthmaticasthmatic
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Status Asthmaticus in ChildrenStatus Asthmaticus in Children
EpidemiologyEpidemiology
PathophysiologyPathophysiology
Presentation and assessmentPresentation and assessment
TreatmentTreatmentConventionalConventional
General, -agonists, steroids, anticholinergicsGeneral, -agonists, steroids, anticholinergics
AdvancedAdvanced
Mechanical ventilation, ketamine, inhalational anestheticsMechanical ventilation, ketamine, inhalational anesthetics
Unusual/UnprovenUnusual/UnprovenTheophylline, magnesium, LTRAs, heliox, bronchoscopyTheophylline, magnesium, LTRAs, heliox, bronchoscopy
Status asthmaticusStatus asthmaticus : Treatment: Treatment
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OxygenOxygen
Deliver high flow oxygen, asDeliver high flow oxygen, as
severe asthma causes V/Qsevere asthma causes V/Q
mismatch (shunt)mismatch (shunt)
Oxygen will not suppress respiratory drive inOxygen will not suppress respiratory drive in
children with asthmachildren with asthmaSchiff M. Clin Chest Med 1980;1(1):85-9Schiff M. Clin Chest Med 1980;1(1):85-9
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FluidFluid
Judicious use of IV fluid necessaryJudicious use of IV fluid necessary
Most asthmatics are dehydrated onMost asthmatics are dehydrated on
presentations - rehydrate topresentations - rehydrate to eueuvolemiavolemia
OverOverhydration may lead to pulmonaryhydration may lead to pulmonaryedemaedema
SIADH may be common in severe asthmaSIADH may be common in severe asthmaBaker JW. Mayo Clin Proc 1976;51(1):31-4Baker JW. Mayo Clin Proc 1976;51(1):31-4
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AntibioticsAntibiotics
Most infections precipitating asthmaMost infections precipitating asthma
are viralare viral
Antibiotics are not routinelyAntibiotics are not routinely
indicatedindicated
Johnston SL. Pediatr Pulmonol Suppl 1999;18:141-3Johnston SL. Pediatr Pulmonol Suppl 1999;18:141-3 ??
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-Agonists-Agonists
-receptor agonists stimulate -receptor agonists stimulate 22-receptors on bronchial smooth muscle and mediate muscle relaxation-receptors on bronchial smooth muscle and mediate muscle relaxation
EpinephrineEpinephrine
IsoproterenolIsoproterenol
TerbutalineTerbutaline
AlbuterolAlbuterol
Relatively Relatively 22selectiveselective
Significant Significant 11cardiovascularcardiovascular
effectseffects
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-Agonists-Agonists
Less than 10% of nebulized drug reach theLess than 10% of nebulized drug reach the
lung under ideal conditionslung under ideal conditionsBisgaard H. J Asthma 1997;34(6):443-67Bisgaard H. J Asthma 1997;34(6):443-67
Drug delivery depends onDrug delivery depends on
Breathing patternBreathing pattern
Tidal volumeTidal volume
Nebulizer type and gas flowNebulizer type and gas flow
Status asthmaticusStatus asthmaticus : Treatment: Treatment
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-Agonists -Agonists
Delivery of nebulized drugDelivery of nebulized drug
Only particlesOnly particles
betweenbetween0.8 3 0.8 3 mmareare
deposited in alveolideposited in alveoli Correct gas flow rate isCorrect gas flow rate is
crucialcrucial
Most devices require 10-12Most devices require 10-12
L/min gas flow to generateL/min gas flow to generatecorrect particle sizecorrect particle size
Status asthmaticusStatus asthmaticus : Treatment: Treatment
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-Agonists -Agonists
Continuous nebulization is superior toContinuous nebulization is superior to
intermittent nebulizationintermittent nebulization
More rapid improvementMore rapid improvement
More cost effectiveMore cost effective
More patient friendlyMore patient friendly
Papo MC. Crit Care Med 1993;21:1479-86Papo MC. Crit Care Med 1993;21:1479-86
Ackerman AD. Crit Care Med 1993;21:1422-4Ackerman AD. Crit Care Med 1993;21:1422-4
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-Agonists -Agonists
DosageDosage
Intermittent nebulizationIntermittent nebulization
2.5 - 5 mg (0.5 - 1 ml of 0.5% solution), dilute with N2.5 - 5 mg (0.5 - 1 ml of 0.5% solution), dilute with N
to 3 mlto 3 ml
Prediluted: 2.5 mg as 3ml of 0.083% solutionPrediluted: 2.5 mg as 3ml of 0.083% solutionHigh dose: use up to undiluted 5% solutionHigh dose: use up to undiluted 5% solution
Continuous nebulizationContinuous nebulization
4-40 mg/hr4-40 mg/hr
High dose: up to undiluted 5% solution ( 150 mg/hHigh dose: up to undiluted 5% solution ( 150 mg/h
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-Agonists -Agonists
Intravenous - AgonistIntravenous - Agonist
Consider for patients with severe air flowConsider for patients with severe air flow
limitation who remain unresponsive tolimitation who remain unresponsive to
nebulized albuterolnebulized albuterolTerbutaline is i.v. -agonist of choice in USTerbutaline is i.v. -agonist of choice in US
Dosage: 0.1 - 10Dosage: 0.1 - 10 g/kg/ming/kg/min
Stephanopoulos DE. Crit Care Med 1998;26(10):1744-8Stephanopoulos DE. Crit Care Med 1998;26(10):1744-8
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-Agonists -Agonists
Side effectsSide effects
TachycardiaTachycardia
Agitation, tremorAgitation, tremor
HypokalemiaHypokalemia
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-Agonists -Agonists
Cardiac side effectsCardiac side effects
Myocardial ischemia known to occur with i.v.Myocardial ischemia known to occur with i.v.
isoproterenolisoproterenol
No significant cardiovascular toxicity with i.v.No significant cardiovascular toxicity with i.v.terbutaline (prospective study in children withterbutaline (prospective study in children with
severe asthma)severe asthma)Chiang VW. J Pediatr 2000;137(1):73-7Chiang VW. J Pediatr 2000;137(1):73-7
Tachycardia (and tremor) show tachyphylaxis,Tachycardia (and tremor) show tachyphylaxis,
bronchodilation does notbronchodilation does notLipworth BJ. Am Rev Respir Dis 1989;140(3):586-92Lipworth BJ. Am Rev Respir Dis 1989;140(3):586-92
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SteroidsSteroids
Asthma is an inflammatory diseaseAsthma is an inflammatory disease Steroids are a mandatory element of firstSteroids are a mandatory element of first
line therapy regimenline therapy regimen (few exceptions only)(few exceptions only)
-20
0
20
40
60
80
100
120
140
-5 0 6 12 18 24
!ours
6(.1
%teroids
la"e3o
Fanta CH: Am J Med 1983;74:845Fanta CH: Am J Med 1983;74:845
Effect of i.v.Effect of i.v.
hydrocortisonehydrocortisone
vs. placebovs. placebo
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SteroidsSteroids
Hydrocortisone 4-8 mg/kg x 1, then 2-4Hydrocortisone 4-8 mg/kg x 1, then 2-4
mg/kg q 6mg/kg q 6
Methylprednisolone 2 mg/kg x1, then 0.5-1Methylprednisolone 2 mg/kg x1, then 0.5-1
mg/kg q 4-6mg/kg q 4-6
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SteroidsSteroids
Significant side effectsSignificant side effects HyperglycemiaHyperglycemia
HypertensionHypertension
Acute psychosisAcute psychosis
Unusual or unusually severe infectionsUnusual or unusually severe infectionsSteroids contraindicated with active orSteroids contraindicated with active or
recent exposure to chickenpoxrecent exposure to chickenpox
Allergic reactionAllergic reaction
Reported with methylprednisolone,Reported with methylprednisolone,
hydrocortisone and prednisonehydrocortisone and prednisone**
** Vanpee D. Ann Emerg Med 1998;32(6):754. Kamm GL. Ann Pharmacother 1999;33(4):451-60.Vanpee D. Ann Emerg Med 1998;32(6):754. Kamm GL. Ann Pharmacother 1999;33(4):451-60. SchonwaldSchonwaldS. Am J Emerg Med 1999;17(6):583-5. Judson MA. Chest 1995;107(2):563-5.S. Am J Emerg Med 1999;17(6):583-5. Judson MA. Chest 1995;107(2):563-5.
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Anticholinergics - IpratropiumAnticholinergics - Ipratropium
Quaternary atropine derivativeQuaternary atropine derivative
Not absorbed systemicallyNot absorbed systemically
Thus minimal cardiac effectsThus minimal cardiac effects(But you will find a fixed/dilated pupil if the nebulizer mask slips over(But you will find a fixed/dilated pupil if the nebulizer mask slips over
an eye!)an eye!)
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AnticholinergicsAnticholinergics
Change in FEVChange in FEV11is significantly greater whenis significantly greater when
ipratropium was added to -agonists (199 adultsipratropium was added to -agonists (199 adultsRebuck AS: Am J Med 1987;82:59Rebuck AS: Am J Med 1987;82:59
Highly significant improvement in pulmonaryHighly significant improvement in pulmonary
function when ipratropium was added tofunction when ipratropium was added to
albuterol (128 children). Sickest asthmaticsalbuterol (128 children). Sickest asthmatics
experienced greatest improvementexperienced greatest improvementSchuh S. J Pediatr 1995;126(4):639-45Schuh S. J Pediatr 1995;126(4):639-45
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IpratropiumIpratropium
Dose-Response Curve in Children (n=19, age 11-Dose-Response Curve in Children (n=19, age 11-17 yrs)17 yrs)
0
081
082083
084
7.5 25 75 250
ose 9mi"ro#rams:ose 9mi"ro#rams:
&era#e in"rease in (.&era#e in"rease in (.119oer 4 hrs:9oer 4 hrs:
Davis A: J Pediatr 1984;105:1002Davis A: J Pediatr 1984;105:1002
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IpratropiumIpratropium
Nebulize 250 - 500Nebulize 250 - 500 g every 4-6 hoursg every 4-6 hours
Schuh S. J Pediatr 1995;126(4):639-45Schuh S. J Pediatr 1995;126(4):639-45
Goodman and Gilman's. 9th ed. New York: McGraw-Hill; 1996Goodman and Gilman's. 9th ed. New York: McGraw-Hill; 1996
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Intubation, VentilationIntubation, Ventilation
Absolute indications:Absolute indications:
Cardiac or respiratory arrestCardiac or respiratory arrest
Severe hypoxiaSevere hypoxia
Rapid deterioration in mental stateRapid deterioration in mental state
Respiratory acidosis does not dictateRespiratory acidosis does not dictate
intubationintubation
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Why hesitate to intubate theWhy hesitate to intubate the
asthmatic child?asthmatic child? Tracheal foreign bodyTracheal foreign body
aggravates bronchospasmaggravates bronchospasm
Positive pressure ventilationPositive pressure ventilation
increases risk of barotraumaincreases risk of barotraumaand hypotensionand hypotensionTuxen DV. Am Rev Respir Dis 1987;136(4):872-9Tuxen DV. Am Rev Respir Dis 1987;136(4):872-9
> 50% of morbidity/mortality during severe asthma> 50% of morbidity/mortality during severe asthma
occurs during or immediately after intubationoccurs during or immediately after intubationZimmerman JL. Crit Care Med 1993;21(11):1727-30Zimmerman JL. Crit Care Med 1993;21(11):1727-30
Status asthmaticusStatus asthmaticus : Treatment: Treatment
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IntubationIntubation
Preoxygenate, decompress stomachPreoxygenate, decompress stomach
Sedate (consider ketamine)Sedate (consider ketamine)
Neuromuscular blockade (may avoidNeuromuscular blockade (may avoid
large swings in airway/pleural pressure)large swings in airway/pleural pressure)
Rapid orotracheal intubation (considerRapid orotracheal intubation (consider
cuffed tube)cuffed tube)
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Immediately after intubationImmediately after intubation
Expect hypotension, circulatory depressionExpect hypotension, circulatory depression
Allow long expiratory timeAllow long expiratory time
Avoid overzealous manual breathsAvoid overzealous manual breaths
Consider volume administrationConsider volume administration
Consider pneumothoraxConsider pneumothorax
Consider endotracheal tube obstruction (++Consider endotracheal tube obstruction (++
secretions)secretions)
Status asthmaticusStatus asthmaticus : Treatment: Treatment
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Mechanical ventilationMechanical ventilation
Positive pressure ventilation worsensPositive pressure ventilation worsenshyperinflation/risk of barotraumahyperinflation/risk of barotrauma
Thoughtful strategies include:Thoughtful strategies include:Pressure-limited ventilation, TV 8-12 ml/kg, short TPressure-limited ventilation, TV 8-12 ml/kg, short T ii, rate, rate
8-12/min (permissive hypercapnia)8-12/min (permissive hypercapnia)Cox RG. Pediatr Pulmonol 1991;11(2):120-6Cox RG. Pediatr Pulmonol 1991;11(2):120-6
Pressure support ventilation using PS=20-30 cmHPressure support ventilation using PS=20-30 cmH22O (mayO (may
decrease hyperinflation by allowing active exhalation)decrease hyperinflation by allowing active exhalation)
Wetzel RC. Crit Care Med 1996;24(9):1603-5Wetzel RC. Crit Care Med 1996;24(9):1603-5
Status asthmaticusStatus asthmaticus : Treatment: Treatment
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KetamineKetamine
Dissociative anesthetic with strongDissociative anesthetic with strong
analgesic effectanalgesic effect
Direct bronchodilating actionDirect bronchodilating action
Useful for induction (2 mg/kg i.v.) as well asUseful for induction (2 mg/kg i.v.) as well as
continuous infusion (0.5 - 2 mg/kg/hr)continuous infusion (0.5 - 2 mg/kg/hr)
Induces bronchorrhea, emergence reactionInduces bronchorrhea, emergence reaction
Status asthmaticusStatus asthmaticus : Treatment: Treatment
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Inhalational anestheticsInhalational anesthetics
Halothane, isoflurane have bronchodilatingHalothane, isoflurane have bronchodilating
effecteffect
Halothane may cause hypotension,Halothane may cause hypotension,
dysrhythmiadysrhythmia
Requires scavenging system, continuousRequires scavenging system, continuous
gas analysisgas analysis
Status asthmaticusStatus asthmaticus : Treatment: Treatment
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TheophyllineTheophylline
Role in children with severe asthmaRole in children with severe asthma
remains controversialremains controversial
Narrow therapeutic rangeNarrow therapeutic range
High risk of serious adverse effectsHigh risk of serious adverse effects
Mechanism of effect in asthma remainsMechanism of effect in asthma remains
unclearunclear
Status asthmaticusStatus asthmaticus : Treatment: Treatment
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TheophyllineTheophylline
May have a role in selected, critically ill childrenMay have a role in selected, critically ill childrenwith asthma unresponsive to conventionalwith asthma unresponsive to conventional
therapy:therapy: Randomized, placebo-controlled, blinded trial (n=163) in children withRandomized, placebo-controlled, blinded trial (n=163) in children with
severe status asthmaticussevere status asthmaticus
Theophylline group had greater improvement in PFTs and OTheophylline group had greater improvement in PFTs and O22saturationsaturation No difference in lengthNo difference in length
of PICU stayof PICU stay
Theophylline group had signifi-Theophylline group had signifi-
cantly more N/Vcantly more N/V
Yung M. Arch Dis Child 1998;79(5):405-10.Yung M. Arch Dis Child 1998;79(5):405-10.
0
1020
30
40
50
60
Prior 6 hr 12 hr 24 hr
FEV 1 (%)
Placebo
Theophylline
Status asthmaticusStatus asthmaticus : Treatment: Treatment
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MagnesiumMagnesium
Smooth-muscle relaxation by inhibition ofSmooth-muscle relaxation by inhibition of
calcium uptake (=bronchodilator)calcium uptake (=bronchodilator)
Dosage recommendation: 25 - 75 mg/kg i.v.Dosage recommendation: 25 - 75 mg/kg i.v.over 20 minutesover 20 minutes
Status asthmaticusStatus asthmaticus
: Treatment: Treatment
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MagnesiumMagnesium
Several anecdotal reportsSeveral anecdotal reportsOnly one randomized pediatric trialOnly one randomized pediatric trial Randomized, placebo-controlled, blinded trial (n=31) in childrenRandomized, placebo-controlled, blinded trial (n=31) in children
with acute asthma in ER (MgSOwith acute asthma in ER (MgSO4425 mg/kg i.v. for 20 min)25 mg/kg i.v. for 20 min)
Magnesium group had significantly greater improvement inMagnesium group had significantly greater improvement in
FEVFEV11/PEFR/FVC/PEFR/FVC Magnesium group more likelyMagnesium group more likely
to be discharged hometo be discharged home
No adverse effectsNo adverse effects
Ciarallo L. J Pediatr 1996;Ciarallo L. J Pediatr 1996;129129(6):809-14.(6):809-14.
0
10
20
30
40
50
60
50 min 80 min 110 min
Placebo
Magnesium
Status asthmaticusStatus asthmaticus
Leukotriene receptor antagonistsLeukotriene receptor antagonists
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Leukotriene receptor antagonistsLeukotriene receptor antagonists
(LTRAs)(LTRAs)
Asthmatic children have increasedAsthmatic children have increased
leukotriene levels (blood, urine) duringleukotriene levels (blood, urine) during
an attack. Level falls as attack resolvesan attack. Level falls as attack resolvesSampson AP. Ann N Y Acad Sci 1991;629:437-9.Sampson AP. Ann N Y Acad Sci 1991;629:437-9.
LTRA administration is associated withLTRA administration is associated with
improvement in lung function inimprovement in lung function in
asthmaticsasthmatics
Gaddy JN. Am Rev Respir Dis 1992;146(2):358-63.Gaddy JN. Am Rev Respir Dis 1992;146(2):358-63.
Status asthmaticusStatus asthmaticus
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LTRAsLTRAs
Steroid administration to asthmatics hasSteroid administration to asthmatics has
little effect on leukotriene levelslittle effect on leukotriene levelsO'Shaughnessy KM. Am Rev Respir Dis 1993;147(6 Pt 1):1472-6.O'Shaughnessy KM. Am Rev Respir Dis 1993;147(6 Pt 1):1472-6.
Thus, LTRAs may offer additional benefitsThus, LTRAs may offer additional benefits
to asthmatics on steroidsto asthmatics on steroidsReiss TF. Arch Intern Med 1998;158(11):1213-20.Reiss TF. Arch Intern Med 1998;158(11):1213-20.
Status asthmaticusStatus asthmaticus
Intravenous LTRAs in moderateIntravenous LTRAs in moderate
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Intravenous LTRAs in moderateIntravenous LTRAs in moderate
to severe asthmato severe asthma
A single dose of i.v.A single dose of i.v.
montelukastmontelukast
(Singulair(Singulair) was) was
associated withassociated with
significantsignificant
improvement in lungimprovement in lung
function compared tofunction compared to
standard therapystandard therapy
Camargo CA, Jr. Am J Respir Crit Care Med 2003;167(4):528-33.Camargo CA, Jr. Am J Respir Crit Care Med 2003;167(4):528-33.
Status asthmaticusStatus asthmaticus
A i i i
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LTRAs Remaining questionsLTRAs Remaining questions
Will they offer added benefit in the acute, severeWill they offer added benefit in the acute, severeasthmatic child already onasthmatic child already on -agonists, steroids,-agonists, steroids,anticholinergicsanticholinergics ?? More rapid improvement in lung function/clinical score?More rapid improvement in lung function/clinical score?
Reduced/shortened hospitalization?Reduced/shortened hospitalization?
Fewer PICU admissions?Fewer PICU admissions?
Cost ?Cost ?
Adverse effects ?Adverse effects ?
Status asthmaticusStatus asthmaticus
H li O (H li )
: Treatment: Treatment
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Helium - Oxygen (Heliox)Helium - Oxygen (Heliox)
Helium lowers gas density (if at leastHelium lowers gas density (if at least
60% helium fraction)60% helium fraction)
Reduces resistance during turbulent flowReduces resistance during turbulent flow
Renders turbulent flow less likely toRenders turbulent flow less likely tooccuroccur
Status asthmaticusStatus asthmaticus
H liH li
: Treatment: Treatment
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HelioxHeliox
Anecdotal reports of improved respiratoryAnecdotal reports of improved respiratory
mechanics in non-intubated and intubatedmechanics in non-intubated and intubated
asthmatic childrenasthmatic children
Prospective, randomized, blinded cross-overProspective, randomized, blinded cross-overstudy of heliox in non-intubated childrenstudy of heliox in non-intubated children
with severe asthma (n=11) : no effect onwith severe asthma (n=11) : no effect on
respiratory mechanics or asthma scorerespiratory mechanics or asthma score
Carter ER. Chest 1996;109(5):1256-61.Carter ER. Chest 1996;109(5):1256-61.
Status asthmaticusStatus asthmaticus
H liH li
: Treatment: Treatment
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HelioxHeliox
Helium-oxygen (80:20) decreased pulsusHelium-oxygen (80:20) decreased pulsus
paradoxus and increased PEFR in aparadoxus and increased PEFR in a
controlled trial of adult patientscontrolled trial of adult patientsManthous CA. Am J Respir Crit Care Med 1995,151:310-314Manthous CA. Am J Respir Crit Care Med 1995,151:310-314
Heliox may worsen dynamic hyperinflationHeliox may worsen dynamic hyperinflationMadison JM. Chest 1995,107:597-598Madison JM. Chest 1995,107:597-598
Status asthmaticusStatus asthmaticus
Bronchoscopy bronchialBronchoscopy bronchial
: Treatment: Treatment
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Bronchoscopy, bronchialBronchoscopy, bronchial
lavagelavageMarked mucus plugging may renderMarked mucus plugging may render
bronchodilating and anti-inflammatorybronchodilating and anti-inflammatory
therapy ineffectivetherapy ineffective
Plastic bronchitis has been described inPlastic bronchitis has been described inasthmatic childrenasthmatic children
Combined bronchoscopy/lavage has beenCombined bronchoscopy/lavage has been
used in desperately ill asthmatic childrenused in desperately ill asthmatic children
Status asthmaticusStatus asthmaticus
SS
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SummarySummary
Severe asthma in children is increasing in prevalenceSevere asthma in children is increasing in prevalence
and mortalityand mortality
Aggressive treatment with -agonist, steroids andAggressive treatment with -agonist, steroids and
anticholinergic is warranted even in the sick-appearinganticholinergic is warranted even in the sick-appearing
childchild Avoid intubation if possibleAvoid intubation if possible
Mechanical ventilation will worsen bronchospasm andMechanical ventilation will worsen bronchospasm and
hyperinflationhyperinflation
Use low morbidity approach to mechanical ventilationUse low morbidity approach to mechanical ventilation
Status asthmaticusStatus asthmaticus
P tiP ti
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PreventionPrevention
Steps toward preventionSteps toward prevention
1.1. Identify patients as at riskIdentify patients as at risk
2.2. Tell them about their risksTell them about their risks
3.3. Organize treatment planOrganize treatment plan
4.4. Facilitate access to continued careFacilitate access to continued care
Status asthmaticusStatus asthmaticus
C S i (1)Case Scenario (1)
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Case Scenario (1)Case Scenario (1)
A 6 y o black male with previous history of asthma isA 6 y o black male with previous history of asthma is
admitted with severe respiratory distress. He is wheezing,admitted with severe respiratory distress. He is wheezing,
RR is 40/min, HR 145/min. He sits upright, leans forward,RR is 40/min, HR 145/min. He sits upright, leans forward,
has retractions and looks very anxious. He correctly tellshas retractions and looks very anxious. He correctly tells
you his name and phone #, but has to take a breath afteryou his name and phone #, but has to take a breath after
every few words.every few words.
Discuss your initialDiscuss your initial therapeutictherapeuticapproach.approach.
Status asthmaticusStatus asthmaticus
C S i (2)Case Scenario (2)
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Case Scenario (2)Case Scenario (2)Which of the following are mandatory in this child with severeWhich of the following are mandatory in this child with severe
asthma?asthma?(You may chose none, more than one or all)(You may chose none, more than one or all)
Arterial blood gas analysis (to detect onset of respiratoryArterial blood gas analysis (to detect onset of respiratory
acidosis)acidosis)
Continuous pulse oximetryContinuous pulse oximetry Chest radiograph (to rule out pneumomediastinum/ thorax)Chest radiograph (to rule out pneumomediastinum/ thorax)
Frequent determination of peak expiratory flow rateFrequent determination of peak expiratory flow rate
White blood cell count with differential (to assess need forWhite blood cell count with differential (to assess need for
antibiotics)antibiotics)
Status asthmaticusStatus asthmaticus
Case Scenario (3)Case Scenario (3)
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Case Scenario (3)Case Scenario (3)
Given his current presentation: does this child need to beGiven his current presentation: does this child need to be
intubated and mechanically ventilated?intubated and mechanically ventilated?
Discuss indications for intubation/mechanical ventilationDiscuss indications for intubation/mechanical ventilation
in the child with severe status asthmaticus.in the child with severe status asthmaticus.
Status asthmaticusStatus asthmaticus
Case Scenario (4)Case Scenario (4)
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Case Scenario (4)Case Scenario (4)When nebulizing drugs during status asthmaticus, the followingWhen nebulizing drugs during status asthmaticus, the following
statement about gas flow rates is CORRECT:statement about gas flow rates is CORRECT:
A.A. The higher the gas flow rate through the nebulizer, theThe higher the gas flow rate through the nebulizer, the
more particles will be deposited in the patients alveolarmore particles will be deposited in the patients alveolar
spacespace
B.B. Most devices require a gas flow rate of 10-12 L/min toMost devices require a gas flow rate of 10-12 L/min to
generate optimal particle sizegenerate optimal particle size
C.C. Gas flow rates above 5 L/min should be avoided toGas flow rates above 5 L/min should be avoided to
maintain laminar flow in the nebulizer outputmaintain laminar flow in the nebulizer output
D.D. The nebulizer device should not be driven by 100% oxygenThe nebulizer device should not be driven by 100% oxygen
Status asthmaticusStatus asthmaticus
Case Scenario (5)Case Scenario (5)
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Case Scenario (5)Case Scenario (5)In addition to administration of continuously nebulized beta-In addition to administration of continuously nebulized beta-
agonist and intermittent anticholinergic agonist, which of theagonist and intermittent anticholinergic agonist, which of the
following is almost mandatory? Discuss pros and cons for each.following is almost mandatory? Discuss pros and cons for each.
A.A. Intravenous bolus of aminophylline, followed byIntravenous bolus of aminophylline, followed by
infusioninfusion
B.B. Intravenous corticosteroidIntravenous corticosteroid
C.C. Intravenous broad spectrum antibioticIntravenous broad spectrum antibiotic
D.D. Intravenous beta-agonist infusionIntravenous beta-agonist infusion
E.E. Inhaled helium-oxygen mixtureInhaled helium-oxygen mixture
Status asthmaticusStatus asthmaticus
Case Scenario (6)Case Scenario (6)
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Case Scenario (6)Case Scenario (6)
After 3 hours of therapy in the PICU, including high doseAfter 3 hours of therapy in the PICU, including high dose
continuous albuterol, intermittent ipratropium, I.v.continuous albuterol, intermittent ipratropium, I.v.
methylprednisolone as well as two infusions of magnesiummethylprednisolone as well as two infusions of magnesium
sulfate, the child becomes obtunded. His Osulfate, the child becomes obtunded. His O22saturationssaturations
begin to drop below 85%. Is this an indication forbegin to drop below 85%. Is this an indication for
intubation/mechanical ventilation?intubation/mechanical ventilation?
If so, describe your approach to intubating this child.If so, describe your approach to intubating this child.
How to prepare? Drugs? ETT size, route? Anticipated problems /How to prepare? Drugs? ETT size, route? Anticipated problems /
complications? Initial pattern of ventilation?complications? Initial pattern of ventilation?
Status asthmaticusStatus asthmaticus
Case Scenario (7)Case Scenario (7)
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Case Scenario (7)Case Scenario (7)
After you connect the child to the ventilator, he developsAfter you connect the child to the ventilator, he develops
marked arterial hypotension.marked arterial hypotension.
What is your differential diagnosis?What is your differential diagnosis?
What should you do?What should you do?
Status asthmaticusStatus asthmaticus
Suggested Reading (part 1):1 Laitinen LA Heino M Laitinen A et al Damage of airway epithelium and bronchial reactivity in patients with asthma
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1. Laitinen LA, Heino M, Laitinen A, et al. Damage of airway epithelium and bronchial reactivity in patients with asthma.
Am Rev Respir Dis 1985;131(4):599-606.
2. Beakes DE. The use of anticholinergics in asthma. J Asthma 1997;34(5):357-68.
3. Barnes PJ. Beta-adrenergic receptors and their regulation. Am J Respir Crit Care Med 1995;152(3):838-60.
4. Miro A, Pinsky M. Cardiopulmonary Interactions. In: Fuhrman B, Zimmerman J, editors. Pediatric Critical Care.Second ed. St. Louis: Mosby; 1998. p. 250-60.
5. Stalcup SA, Mellins RB. Mechanical forces producing pulmonary edema and acute asthma. N Engl J Med
1977;297(11):592-6.
6. Rebuck AS, Pengelly LD. Development of pulsus paradoxus in the presence of airway obstruction. N Engl J Med
1973;288(2):66-9.
7. Papo MC, Frank J, Thompson AE. A prospective, randomized study of continuous versus intermittent nebulized
albuterol for severe status asthmaticus in children. Crit Care Med 1993;21:1479-86.
8. Katz RW, Kelly HW, Crowley MR, et al. Safety of continuous nebulized albuterol for bronchospasm in infants andchildren [published erratum appears in Pediatrics 1994 Feb;93(2):A28]. Pediatrics 1993;92(5):666-9.
9. Schuh S, Johnson DW, Callahan S, et al. Efficacy of frequent nebulized ipratropium bromide added to frequent high-do
albuterol therapy in severe childhood asthma. J Pediatr 1995;126(4):639-45.
10. Fanta CH, Rossing TH, McFadden ER. Glucocorticoids in acute asthma: A critical controlled trial. Am J Med
1983;74:845-51.
Status asthmaticusStatus asthmaticus
Suggested Reading (part 2):i Gi S i i i i
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11. Klein-Gitelman MS, Pachman LM. Intravenous corticosteroids: adverse reactions are more variable than
expected in children. J Rheumatol 1998;25(10):1995-2002.
12. Stephanopoulos DE, Monge R, Schell KH, et al. Continuous intravenous terbutaline for pediatric status
asthmaticus. Crit Care Med 1998;26(10):1744-8.13. Chiang VW, Burns JP, Rifai N, et al. Cardiac toxicity of intravenous terbutaline for the treatment of severe
asthma in children: a prospective assessment. J Pediatr 2000;137(1):73-7.
14. Ciarallo L, Sauer AH, Shannon MW. Intravenous magnesium therapy for moderate to severe pediatric
asthma: results of a randomized, placebo-controlled trial. J Pediatr 1996;129(6):809-14.
15. Pabon H, Monem G, Kissoon N. Safety and efficacy of magnesium sulfate infusions in children with status
asthmaticus. Pediatr Emerg Care 1994;10:200-3.
16. Yung M, South M. Randomised controlled trial of aminophylline for severe acute asthma. Arch Dis Child
1998;79(5):405-10.
17. Tuxen DV, Lane S. The effects of ventilatory pattern on hyperinflation, airway pressures, and circulation in
mechanical ventilation of patients with severe airflow obstruction. Am Rev Respir Dis 1987;136(4):872-9.
18. Wetzel RC. Pressure-support ventilation in children with severe asthma. Crit Care Med 1996;24(9):1603-5.
19. Ibsen LM, Bratton SL. Current therapies for severe asthma exacerbations in children. New Horiz
1999;7(3):312-25.
20. Werner HA. Status asthmaticus in children: a review. Chest 2001;119(6):1913-29.