status asthmaticus in children

7/18/2019 status asthmaticus in children

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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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EpidemiologyEpidemiology

PathophysiologyPathophysiology

Presentation and AssessmentPresentation and AssessmentTreatmentTreatment


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PrevalencePrevalence

MorbidityMorbidity

MortalityMortalityRisk factorsRisk factors


Presentation and assessmentPresentation and assessment

TreatmentTreatment


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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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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



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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



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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



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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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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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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



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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



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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



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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)



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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


S h i iP th h i l


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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


St t th tiSt t th ti P th h i lP th h i l


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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


St t th tiSt t th ti P th h i lP th h i l


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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


St t th tiStatus asthmaticus Pathoph siolog: Pathophysiology


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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


Status asthmaticusStatus asthmaticus : Pathophysiology: Pathophysiology


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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




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+e#atie intrapleural+e#atie intrapleural

pressurepressure

ulmonary edemaulmonary edema ulsus parado)usulsus parado)us

!yperinflation!yperinflation

!ypotension!ypotension

&ltered hemodynami"s&ltered hemodynami"s




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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#



: Presentation: Presentation


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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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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



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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



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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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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



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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



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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



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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)



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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



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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



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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



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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



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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



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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


: 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


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.



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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.


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.


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 ?


H li O (H li )



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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


H liH li



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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.


H liH li



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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


Bronchoscopy bronchialBronchoscopy bronchial



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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


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


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


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.


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)




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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.




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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




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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




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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?




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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?


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.


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.

status asthmaticus in children

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