status asthmaticus in children

©hwerner©hwerner

Status Asthmaticus in ChildrenStatus Asthmaticus in ChildrenStatus Asthmaticus in ChildrenStatus Asthmaticus in Children

Heinrich WernerHeinrich Werner

Pediatric Critical CarePediatric Critical Care

University of Kentucky Children’s University of Kentucky Children’s HospitalHospital

Status asthmaticusStatus asthmaticus

ObjectivesObjectivesObjectivesObjectivesThe participant will increase his/herThe participant will increase his/her

Awareness of rising morbidity/mortality of severe asthma in Awareness of rising morbidity/mortality of severe asthma in childrenchildren

Ability to define who is at risk for dying Ability to define who is at risk for dying Understanding of the pathologic, metabolic and Understanding of the pathologic, metabolic and

biomechanical eventsbiomechanical events Ability to predict respiratory failure and to determine the Ability to predict respiratory failure and to determine the

need for early transferneed for early transfer Ability to tailor the therapeutic regimen according to Ability to tailor the therapeutic regimen according to

severity and progression of status asthmaticusseverity and progression of status asthmaticus



EpidemiologyEpidemiology

PathophysiologyPathophysiology

Presentation and AssessmentPresentation and Assessment

TreatmentTreatment



EpidemiologyEpidemiologyPrevalencePrevalence

MorbidityMorbidity

MortalityMortality

Risk factorsRisk factors


Presentation and assessmentPresentation and assessment

TreatmentTreatment


PrevalencePrevalencePrevalencePrevalenceThe prevalence of pediatric asthma in the The prevalence of pediatric asthma in the

US 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 populationMannino DM. MMWR 1998;47(1):1-27Mannino DM. MMWR 1998;47(1):1-27

: Epidemiology: Epidemiology


MorbidityMorbidityMorbidityMorbidity

0

10

20

30

40

50

60

70

1980

1982

1984

1986

1988

1990

1992

Rat

e pe

r 10

,000

pop

ulat

ion

< 1 year

1-4 years

5-14 years

15-24 years

Hospital discharge rates for asthmaHospital discharge rates for asthma

MMWR 1996;45(17):350-3MMWR 1996;45(17):350-3

The morbidity of pediatric asthma in the The morbidity of pediatric asthma in the US is increasingUS is increasing



MortalityMortalityMortalityMortality

0

1

2

3

4

5

6

7

1979-80 1981-83 1984-86 1987-89 1990-92 1993-95

Rat

e pe

r 1,

000,

000

popu

lati

on

0-4 years5-14 years15-34 years

The mortality of pediatric asthma in the US The mortality of pediatric asthma in the US is increasingis increasing

Rates of death in children from asthmaRates of death in children from asthma

Mannino. MMWR 1998;47(1):1-27Mannino. MMWR 1998;47(1):1-27



Risk factors for fatal asthmaRisk factors for fatal asthmaRisk factors for fatal asthmaRisk factors for fatal asthmaMedicalMedical

Previous attack with rapid/severe deterioration or respiratory Previous attack with rapid/severe deterioration or respiratory failure or seizure/loss of consciousnessfailure or seizure/loss of consciousness

PsychosocialPsychosocialDenial, non-complianceDenial, non-compliance

Depression or other psychiatric disorderDepression or other psychiatric disorder

Dysfunctional familyDysfunctional family

Inner city residentInner city resident

EthnicEthnicNon-white childNon-white child





PathophysiologyPathophysiologyCytokinesCytokines

Airway pathologyAirway pathology

Autonomic nervous systemAutonomic nervous system

Pulmonary mechanicsPulmonary mechanics

Cardiopulmonary interactionsCardiopulmonary interactions

MetabolismMetabolism


TreatmentTreatment


PathophysiologyPathophysiologyPathophysiologyPathophysiology

Asthma is primarily an inflammatory diseaseAsthma is primarily an inflammatory disease

Mucous pluggingMucous plugging

Smooth muscle Smooth muscle spasmspasm Airway edemaAirway edema

: Pathophysiology: Pathophysiology


Inflammatory cytokinesInflammatory cytokinesInflammatory cytokinesInflammatory cytokines

Activated mast cells and lymphocytes Activated mast cells and lymphocytes produce pro-inflammatory cytokines produce pro-inflammatory cytokines (histamine, leukotrienes, PAF), which are (histamine, leukotrienes, PAF), which are increased in asthmatics’ airways and increased in asthmatics’ airways and bloodstreambloodstream



Irritable and damaged airwayIrritable and damaged airwayIrritable and damaged airwayIrritable and damaged airwayHypersecretionHypersecretion

Epithelial damage with exposed nerve endingsEpithelial damage with exposed nerve endings

Hypertrophy of goblet cells and mucus glandsHypertrophy of goblet cells and mucus glands



AirwayAirwayAirwayAirwayThe irritable and inflamed airway is susceptible to The irritable and inflamed airway is susceptible to

obstruction triggered byobstruction triggered byAllergensAllergens

InfectionsInfections

Irritants including smokeIrritants including smoke

ExerciseExercise

Emotional stressEmotional stress

GE refluxGE reflux

DrugsDrugs

Other factorsOther factors



Autonomic nervous systemAutonomic nervous systemAutonomic nervous systemAutonomic nervous system

Bronchodilation Bronchoconstriction

SympatheticSympathetic Circulating catecholamines Circulating catecholamines stimulate ß-receptorsstimulate ß-receptors

--

ParasympatheticParasympatheticVagal signals stimulate Vagal signals stimulate bronchodilating Mbronchodilating M2 2 - -

receptorsreceptors

Vagal signals stimulate Vagal signals stimulate bronchoconstricting Mbronchoconstricting M33--

receptorsreceptors

Nonadrenergic-Nonadrenergic-noncholinergic noncholinergic (NANC)(NANC)

Release of bronchodilating Release of bronchodilating neurotransmitters (VIP, NO)neurotransmitters (VIP, NO)

Release of tachykinins (substance Release of tachykinins (substance P, neurokinin A)P, neurokinin A)



Lung mechanicsLung mechanicsLung mechanicsLung mechanics

HyperinflationHyperinflationObstructed small airways cause premature Obstructed small airways cause premature

airway closure, leading to air trapping and airway closure, leading to air trapping and hyperinflationhyperinflation

HypoxemiaHypoxemiaInhomogeneous distribution of affected areas Inhomogeneous distribution of affected areas

results in V/Q mismatch, mostly shuntresults in V/Q mismatch, mostly shunt



Severe airflow Severe airflow obstructionobstruction

Incomplete Incomplete exhalationexhalation

Increased lung Increased lung volumevolume

Increased elastic Increased elastic recoil pressurerecoil pressure

Increased Increased expiratory flowexpiratory flow

Expanded small Expanded small airwaysairways

Decreased expiratory Decreased expiratory resistanceresistance

Compensated:Compensated:Hyperinflation, normocapniaHyperinflation, normocapnia

Decreased expiratory Decreased expiratory resistanceresistance

Decompensated: Decompensated: Severe hyperinflation, hypercapniaSevere hyperinflation, hypercapnia

Worsening Worsening airflow airflow

obstructionobstructionFrom text in : From text in : Tuxen. Am Rev Tuxen. Am Rev Respir Dis Respir Dis 1992;146:11361992;146:1136



Cardiopulmonary interactionsCardiopulmonary interactionsCardiopulmonary interactionsCardiopulmonary interactions

Left ventricular loadLeft ventricular loadSpontaneously breathing children with severe Spontaneously breathing children with severe

asthma have negative intrapleural pressure asthma have negative intrapleural pressure (as low as -35 cmH(as low as -35 cmH22O) during almost the O) during almost the

entire respiratory cycle entire respiratory cycle Stalcup S. N Engl J Med 1977;297:592-6Stalcup S. N Engl J Med 1977;297:592-6

Negative intrapleural pressure causes Negative intrapleural pressure causes increased left ventricular afterload, resulting increased left ventricular afterload, resulting in 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




Right ventricular loadRight ventricular loadHypoxic pulmonary vasoconstriction and lung Hypoxic pulmonary vasoconstriction and lung

hyperinflation lead to increased right hyperinflation 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




Pulsus paradoxusPulsus paradoxusP. paradoxus is the clinical correlate of cardiopulmonary P. paradoxus is the clinical correlate of cardiopulmonary

interaction during asthma. It is defined as exaggeration of interaction during asthma. It is defined as exaggeration of the normal inspiratory drop in systolic BP : normally < 5 the normal inspiratory drop in systolic BP : normally < 5 mmHg, but > 10 mmHg in pulsus paradoxus.mmHg, but > 10 mmHg in pulsus paradoxus.

ExpirExpir Inspir

NlNl

P. paradoxusP. paradoxus

InspirExpirExpir



Pulsus paradoxus correlates with Pulsus paradoxus correlates with severityseverityPulsus paradoxus correlates with Pulsus paradoxus correlates with severityseverity

All patients who presented with FEVAll patients who presented with FEV11 of < 20% of < 20%

(of their best FEV(of their best FEV1 1 while well) had pulsus while well) had pulsus

paradoxusparadoxus

Pierson RN. J Appl Physiol 1972;32(3):391-6Pierson RN. J Appl Physiol 1972;32(3):391-6




Negative intrapleuralNegative intrapleuralpressurepressure

Pulmonary edemaPulmonary edema Pulsus paradoxusPulsus paradoxus

HyperinflationHyperinflation

HypotensionHypotension

Altered hemodynamicsAltered hemodynamics



MetabolismMetabolismMetabolismMetabolism

V/Q mismatchV/Q mismatch

HypoxiaHypoxia

DehydrationDehydration

LactateLactate KetonesKetones

Metabolic acidosisMetabolic acidosis

Increased workIncreased workof breathingof breathing



PresentationPresentationPresentationPresentation

Cough Cough Wheezing Wheezing Increased work of breathingIncreased work of breathing Anxiety Anxiety 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


AssessmentAssessmentAssessmentAssessment

Findings consistent with impending respiratory Findings 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


Clinical Asthma ScoreClinical Asthma ScoreClinical Asthma ScoreClinical Asthma Score 00 1 1 2 2

Cyanosis or Cyanosis 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 AbsentAbsentdecreaseddecreased

Expir wheezingExpir wheezing NoneNone ModerateModerate MarkedMarked

Cerebral functionCerebral function NlNl DepressedDepressed ComaComaAgitatedAgitated

Wood DW. Am J Dis Child 1972;123(3):227-8Wood DW. Am J Dis Child 1972;123(3):227-8

5 = impending resp failure5 = impending resp failure: Assessment: Assessment


Chest X-RayChest X-RayChest 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



ABGABGABGABG

Early status asthmaticus: hypoxemia, Early status asthmaticus: hypoxemia, hypocarbiahypocarbia

Late: hypercarbiaLate: hypercarbia Decision to intubate should not depend on Decision to intubate should not depend on

ABG, but on clinical assessmentABG, but on clinical assessment Frequent ABGs are crucial in the ventilated Frequent ABGs are crucial in the ventilated

asthmaticasthmatic







TreatmentTreatmentConventionalConventional

General, ß-agonists, steroids, anticholinergicsGeneral, ß-agonists, steroids, anticholinergics

AdvancedAdvancedMechanical ventilation, ketamine, inhalational anestheticsMechanical ventilation, ketamine, inhalational anesthetics

Unusual/UnprovenUnusual/UnprovenTheophylline, magnesium, LTRAs, heliox, bronchoscopyTheophylline, magnesium, LTRAs, heliox, bronchoscopy


OxygenOxygenOxygenOxygen

Deliver high flow oxygen, as Deliver high flow oxygen, as severe asthma causes V/Q severe asthma causes V/Q mismatch (shunt)mismatch (shunt)

Oxygen will not suppress respiratory drive in Oxygen will not suppress respiratory drive in children with asthmachildren with asthma

Schiff M. Clin Chest Med 1980;1(1):85-9Schiff M. Clin Chest Med 1980;1(1):85-9

: Treatment: Treatment


FluidFluidFluidFluid

Judicious use of IV fluid necessaryJudicious use of IV fluid necessary Most asthmatics are dehydrated on Most asthmatics are dehydrated on

presentations - rehydrate to presentations - rehydrate to eueuvolemiavolemia OverOverhydration may lead to pulmonary hydration may lead to pulmonary

edemaedema SIADH may be common in severe asthmaSIADH may be common in severe asthma

Baker JW. Mayo Clin Proc 1976;51(1):31-4Baker JW. Mayo Clin Proc 1976;51(1):31-4



AntibioticsAntibioticsAntibioticsAntibiotics

Most infections precipitating asthma Most 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 ??



ß-Agonistsß-Agonistsß-Agonistsß-Agonistsß-receptor agonists stimulate ßß-receptor agonists stimulate ß22-receptors on bronchial smooth muscle and mediate muscle relaxation-receptors on bronchial smooth muscle and mediate muscle relaxation

EpinephrineEpinephrine

IsoproterenolIsoproterenol

TerbutalineTerbutaline

AlbuterolAlbuterol

Relatively ßRelatively ß22 selective selective

Significant ßSignificant ß11 cardiovascular cardiovascular

effectseffects



ß-Agonistsß-Agonistsß-Agonistsß-Agonists

Less than 10% of nebulized drug reach the Less than 10% of nebulized drug reach the lung under ideal conditionslung under ideal conditions

Bisgaard 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



ß -Agonistsß -Agonistsß -Agonistsß -Agonists

Delivery of nebulized drugDelivery of nebulized drug Only particles Only particles

betweenbetweenmmare are deposited in alveolideposited in alveoli

Correct gas flow rate is Correct gas flow rate is crucialcrucial

Most devices require 10-12 Most devices require 10-12 L/min gas flow to generate L/min gas flow to generate correct particle size correct particle size



•ß -Agonistsß -Agonists•ß -Agonistsß -Agonists

Continuous nebulization is superior to Continuous nebulization is superior to intermittent nebulization intermittent nebulization More rapid improvementMore rapid improvementMore cost effectiveMore cost effectiveMore 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




DosageDosage Intermittent nebulizationIntermittent nebulization

2.5 - 5 mg (0.5 - 1 ml of 0.5% solution), dilute with NS 2.5 - 5 mg (0.5 - 1 ml of 0.5% solution), dilute with NS 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 nebulization4-40 mg/hr4-40 mg/hrHigh dose: up to undiluted 5% solution (≈ 150 mg/hr)High dose: up to undiluted 5% solution (≈ 150 mg/hr)




Intravenous ß - AgonistIntravenous ß - AgonistConsider for patients with severe air flow Consider for patients with severe air flow

limitation who remain unresponsive to limitation who remain unresponsive to nebulized albuterolnebulized albuterol

Terbutaline is i.v. ß-agonist of choice in US Terbutaline is i.v. ß-agonist of choice in US

Dosage: 0.1 - 10 Dosage: 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




Side effectsSide effects

TachycardiaTachycardia

Agitation, tremorAgitation, tremor

Hypokalemia Hypokalemia




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 with terbutaline (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 not

Lipworth BJ. Am Rev Respir Dis 1989;140(3):586-92Lipworth BJ. Am Rev Respir Dis 1989;140(3):586-92



SteroidsSteroidsSteroidsSteroids Asthma is an inflammatory diseaseAsthma is an inflammatory disease Steroids are a mandatory element of first Steroids are a mandatory element of first

line therapy regimen line therapy regimen (few exceptions only)(few exceptions only)

-20

0

20

40

60

80

100

120

140

-5 0 6 12 18 24

Hours

FE

V1

%

SteroidsPlacebo

Fanta CH: Am J Med 1983;74:845Fanta CH: Am J Med 1983;74:845

Effect of i.v. Effect of i.v. hydrocortisone hydrocortisone vs. placebovs. placebo



SteroidsSteroidsSteroidsSteroids

Hydrocortisone 4-8 mg/kg x 1, then 2-4 Hydrocortisone 4-8 mg/kg x 1, then 2-4 mg/kg q 6°mg/kg q 6°

Methylprednisolone 2 mg/kg x1, then 0.5-1 Methylprednisolone 2 mg/kg x1, then 0.5-1 mg/kg q 4-6°mg/kg q 4-6°



SteroidsSteroidsSteroidsSteroids

Significant side effectsSignificant side effects HyperglycemiaHyperglycemia Hypertension Hypertension Acute psychosisAcute psychosis Unusual or unusually severe infectionsUnusual or unusually severe infections

Steroids contraindicated with active or Steroids contraindicated with active or recent exposure to chickenpoxrecent exposure to chickenpox

Allergic reactionAllergic reactionReported 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. SchonwaldSchonwald S. 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.



Anticholinergics - IpratropiumAnticholinergics - IpratropiumAnticholinergics - 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!)



AnticholinergicsAnticholinergicsAnticholinergicsAnticholinergics

Change in FEVChange in FEV11 is significantly greater when is significantly greater when

ipratropium was added to ß-agonists (199 adults)ipratropium was added to ß-agonists (199 adults)Rebuck AS: Am J Med 1987;82:59Rebuck AS: Am J Med 1987;82:59

Highly significant improvement in pulmonary Highly significant improvement in pulmonary function when ipratropium was added to function when ipratropium was added to albuterol (128 children). Sickest asthmatics albuterol (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



IpratropiumIpratropiumDose-Response Curve in Children (n=19, age 11-Dose-Response Curve in Children (n=19, age 11-17 yrs)17 yrs)

IpratropiumIpratropiumDose-Response Curve in Children (n=19, age 11-Dose-Response Curve in Children (n=19, age 11-17 yrs)17 yrs)

00.10.20.30.4

7.5 25 75 250

Dose (micrograms)Dose (micrograms)

Average increase in FEVAverage increase in FEV11 (over 4 hrs) (over 4 hrs)

Davis A: J Pediatr 1984;105:1002Davis A: J Pediatr 1984;105:1002



IpratropiumIpratropiumIpratropiumIpratropium

Nebulize 250 - 500 Nebulize 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):639-45Goodman and Gilman's. 9th ed. New York: McGraw-Hill; 1996Goodman and Gilman's. 9th ed. New York: McGraw-Hill; 1996


Intubation, VentilationIntubation, VentilationIntubation, 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 dictate Respiratory acidosis does not dictate intubationintubation



Why hesitate to intubate the Why hesitate to intubate the asthmatic child?asthmatic child?Why hesitate to intubate the Why hesitate to intubate the asthmatic child?asthmatic child?

Tracheal foreign body Tracheal foreign body aggravates bronchospasmaggravates bronchospasm

Positive pressure ventilation Positive pressure ventilation increases risk of barotrauma increases risk of barotrauma and 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



IntubationIntubationIntubationIntubation

Preoxygenate, decompress stomachPreoxygenate, decompress stomach Sedate (consider ketamine)Sedate (consider ketamine) Neuromuscular blockade (may avoid Neuromuscular blockade (may avoid

large swings in airway/pleural pressure)large swings in airway/pleural pressure) Rapid orotracheal intubation (consider Rapid orotracheal intubation (consider

cuffed tube)cuffed tube)



Immediately after intubationImmediately after intubationImmediately 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)



Mechanical ventilationMechanical ventilationMechanical ventilationMechanical ventilation Positive pressure ventilation worsens Positive pressure ventilation worsens

hyperinflation/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 Tii, ,

rate 8-12/min (permissive hypercapnia)rate 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 O

(may decrease hyperinflation by allowing active (may decrease hyperinflation by allowing active exhalation)exhalation)

Wetzel RC. Crit Care Med 1996;24(9):1603-5Wetzel RC. Crit Care Med 1996;24(9):1603-5



KetamineKetamineKetamineKetamine

Dissociative anesthetic with strong Dissociative anesthetic with strong analgesic effectanalgesic effect

Direct bronchodilating actionDirect bronchodilating action

Useful for induction (2 mg/kg i.v.) as well as Useful 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



Inhalational anestheticsInhalational anestheticsInhalational anestheticsInhalational anesthetics

Halothane, isoflurane have bronchodilating Halothane, isoflurane have bronchodilating effecteffect

Halothane may cause hypotension, Halothane may cause hypotension, dysrhythmiadysrhythmia

Requires scavenging system, continuous Requires scavenging system, continuous gas analysisgas analysis



TheophyllineTheophyllineTheophyllineTheophylline

Role in children with severe asthma Role 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 remains Mechanism of effect in asthma remains

unclearunclear



TheophyllineTheophyllineTheophyllineTheophyllineMay have a role in selected, critically ill children May have a role in selected, critically ill children with asthma unresponsive to conventional with asthma unresponsive to conventional therapy:therapy:

Randomized, placebo-controlled, blinded trial (n=163) in children with Randomized, 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 O22 saturation saturation

No difference in length No 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

10

20

30

40

50

60

Prior 6 hr 12 hr 24 hr

FEV 1 (%)

PlaceboTheophylline



MagnesiumMagnesiumMagnesiumMagnesium

Smooth-muscle relaxation by inhibition of Smooth-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



Magnesium Magnesium Magnesium Magnesium Several anecdotal reportsSeveral anecdotal reports

Only one randomized pediatric trial Only one randomized pediatric trial Randomized, placebo-controlled, blinded trial (n=31) in children Randomized, placebo-controlled, blinded trial (n=31) in children

with acute asthma in ER (MgSOwith acute asthma in ER (MgSO44 25 mg/kg i.v. for 20 min) 25 mg/kg i.v. for 20 min)

Magnesium group had significantly greater improvement in Magnesium 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

PlaceboMagnesium



Leukotriene receptor antagonists Leukotriene receptor antagonists (LTRAs)(LTRAs)Leukotriene receptor antagonists Leukotriene receptor antagonists (LTRAs)(LTRAs)

Asthmatic children have increased Asthmatic children have increased leukotriene levels (blood, urine) during leukotriene levels (blood, urine) during an attack. Level falls as attack resolvesan attack. Level falls as attack resolves

Sampson 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 with LTRA administration is associated with improvement in lung function in improvement 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.


LTRAsLTRAsLTRAsLTRAs

Steroid administration to asthmatics has Steroid administration to asthmatics has little effect on leukotriene levelslittle effect on leukotriene levels

O'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 benefits Thus, LTRAs may offer additional benefits to asthmatics on steroidsto asthmatics on steroids

Reiss TF. Arch Intern Med 1998;158(11):1213-20.Reiss TF. Arch Intern Med 1998;158(11):1213-20.


Intravenous LTRAs in moderate Intravenous LTRAs in moderate to severe asthmato severe asthmaIntravenous LTRAs in moderate Intravenous LTRAs in moderate to severe asthmato severe asthma

A single dose of i.v. A single dose of i.v. montelukast montelukast (Singulair(Singulair®) was ®) was associated with associated with significant significant improvement in lung improvement in lung function compared to function 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.


LTRAs – Remaining questionsLTRAs – Remaining questionsLTRAs – Remaining questionsLTRAs – Remaining questions

Will they offer added benefit in the acute, severe Will they offer added benefit in the acute, severe asthmatic child already on asthmatic child already on ß-agonists, steroids, ß-agonists, steroids, anticholinergics anticholinergics ?? 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 ?


Helium - Oxygen (Heliox)Helium - Oxygen (Heliox)Helium - Oxygen (Heliox)Helium - Oxygen (Heliox)

Helium lowers gas density (if at least Helium 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 to Renders turbulent flow less likely to

occuroccur



HelioxHelioxHelioxHeliox

Anecdotal reports of improved respiratory Anecdotal reports of improved respiratory mechanics in non-intubated and intubated mechanics in non-intubated and intubated asthmatic childrenasthmatic children

Prospective, randomized, blinded cross-over Prospective, randomized, blinded cross-over study of heliox in non-intubated children study of heliox in non-intubated children with severe asthma (n=11) : no effect on with 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.



HelioxHelioxHelioxHeliox

Helium-oxygen (80:20) decreased pulsus Helium-oxygen (80:20) decreased pulsus paradoxus and increased PEFR in a paradoxus 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, bronchial Bronchoscopy, bronchial lavagelavageBronchoscopy, bronchial Bronchoscopy, bronchial lavagelavageMarked mucus plugging may render Marked mucus plugging may render

bronchodilating and anti-inflammatory bronchodilating and anti-inflammatory therapy ineffectivetherapy ineffective

““Plastic bronchitis” has been described in Plastic bronchitis” has been described in asthmatic childrenasthmatic children

Combined bronchoscopy/lavage has been Combined bronchoscopy/lavage has been used in desperately ill asthmatic childrenused in desperately ill asthmatic children



SummarySummarySummarySummary

Severe asthma in children is increasing in prevalence Severe asthma in children is increasing in prevalence and mortalityand mortality

Aggressive treatment with ß-agonist, steroids and Aggressive treatment with ß-agonist, steroids and anticholinergic is warranted even in the sick-appearing anticholinergic is warranted even in the sick-appearing childchild

Avoid intubation if possibleAvoid intubation if possible Mechanical ventilation will worsen bronchospasm and Mechanical ventilation will worsen bronchospasm and

hyperinflationhyperinflation Use low morbidity approach to mechanical ventilationUse low morbidity approach to mechanical ventilation


PreventionPreventionPreventionPrevention

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


Case Scenario (1)Case Scenario (1)Case Scenario (1)Case Scenario (1)

A 6 y o black male with previous history of asthma is A 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 tells has retractions and looks very anxious. He correctly tells you his name and phone #, but has to take a breath after you his name and phone #, but has to take a breath after every few words.every few words.

Discuss your initial Discuss your initial therapeutictherapeutic approach. approach.


Case Scenario (2)Case Scenario (2)Case Scenario (2)Case Scenario (2)Which of the following are mandatory in this child with severe Which 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 respiratory Arterial 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 for White blood cell count with differential (to assess need for

antibiotics)antibiotics)



Given his current presentation: does this child need to be Given his current presentation: does this child need to be intubated and mechanically ventilated?intubated and mechanically ventilated?

Discuss indications for intubation/mechanical ventilation Discuss indications for intubation/mechanical ventilation in the child with severe status asthmaticus.in the child with severe status asthmaticus.


Case Scenario (4)Case Scenario (4)Case Scenario (4)Case Scenario (4)When nebulizing drugs during status asthmaticus, the following When 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, the The higher the gas flow rate through the nebulizer, the more particles will be deposited in the patient’s alveolar more particles will be deposited in the patient’s alveolar spacespace

B.B. Most devices require a gas flow rate of 10-12 L/min to Most 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 to Gas 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


Case Scenario (5)Case Scenario (5)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 the agonist 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 by Intravenous 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



After 3 hours of therapy in the PICU, including high dose After 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 magnesium methylprednisolone as well as two infusions of magnesium sulfate, the child becomes obtunded. His Osulfate, the child becomes obtunded. His O22 saturations saturations

begin to drop below 85%. Is this an indication for begin 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?



After you connect the child to the ventilator, he develops After 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):Suggested Reading (part 1):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 and children [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-dose 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):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.