Inpatient Inpatient Management of Management of Asthma Asthma

Michael Bressack, M.D. Michael Bressack, M.D.

DefinitionDefinition• Reversible airway obstructionReversible airway obstruction• Airway inflammationAirway inflammation• Airway hyperresponsivenessAirway hyperresponsiveness• Status asthmaticus = Status asthmaticus =

unresponsive to initial unresponsive to initial nebulized bronchodilatornebulized bronchodilator

PathophysiologyPathophysiology• Airway inflammation- eosinophils, Airway inflammation- eosinophils,

polymorphonuclear cells, lymphocytes, polymorphonuclear cells, lymphocytes, macrophages, mast cellsmacrophages, mast cells

• Proinflammatory mediatorsProinflammatory mediators

• Airway edema, smooth muscle hypertrophy, Airway edema, smooth muscle hypertrophy, exudation, mucous pluggingexudation, mucous plugging

• Hypertrophy of goblet cells and mucous Hypertrophy of goblet cells and mucous glandsglands

Cause of Asthma Cause of Asthma AttackAttack

• Infectious, usually viralInfectious, usually viral

• AllergicAllergic

• IrritantIrritant

Symptoms / SignsSymptoms / Signs• Dyspnea / tachypnea / increased work Dyspnea / tachypnea / increased work

of breathing / difficulty speaking of breathing / difficulty speaking

• Cough Cough

• Wheeze / rhonchi / rales / decreased Wheeze / rhonchi / rales / decreased breath soundsbreath sounds

• Cyanosis Cyanosis

• Abnormal level of consciousnessAbnormal level of consciousness• Pulsus paradoxusPulsus paradoxus

Pulsus ParadoxusPulsus Paradoxus

• Increased pulmonary venous Increased pulmonary venous capacitancecapacitance

• Increased left ventricular afterloadIncreased left ventricular afterload

• Leftward shift of the interventricular Leftward shift of the interventricular septumseptum

• Alterations in pulse oximetry tracingsAlterations in pulse oximetry tracings

Panel A: tracing during respiratory distress- pulsus paradoxus of 16 torr (RWV respiratory waveform variation) Panel B: tracing after treatment / mild respiratory distress- pulsus paradoxus of 8 torr

Hartert T., Chest, 115:477, 1999

Criteria for ICU AdmissionCriteria for ICU Admission

• Severe respiratory symptoms/examSevere respiratory symptoms/exam

• Worsening respiratory symptoms/examWorsening respiratory symptoms/exam

• Abnormal neurologic statusAbnormal neurologic status

• Increasing pC0Increasing pC022

• BarotraumaBarotrauma

• Past history of respiratory failurePast history of respiratory failure

TherapyTherapy

First-line therapyFirst-line therapy

OxygenOxygen

Inhaled Inhaled 2 2 catecholaminecatecholamine

CorticosteroidsCorticosteroids

Ipratropium inhalationIpratropium inhalation

Inhaled Inhaled 2 2 CatecholamineCatecholamine• Albuterol- Albuterol- 2 2 selective bronchodilator of small and selective bronchodilator of small and

large airways (0.15mg/kg/dose)large airways (0.15mg/kg/dose) 22 receptor polymorphism determining receptor polymorphism determining

responsiveness, desensitization, and downregulationresponsiveness, desensitization, and downregulation• Continuous (more rapid response/cost effective) Continuous (more rapid response/cost effective)

(0.4-0.8mg/kg/hr up to 10-20mg/hr), intermittent (0.4-0.8mg/kg/hr up to 10-20mg/hr), intermittent (MDI vs nebulizer)(MDI vs nebulizer)

• Side effects include tachycardia, tremor/ agitation, Side effects include tachycardia, tremor/ agitation, hypoxemia, hypokalemia, arrhythmia, hypotensionhypoxemia, hypokalemia, arrhythmia, hypotension

• Consider subcutaneous epinephrine (0.01ml/kg Consider subcutaneous epinephrine (0.01ml/kg 1/1000) acutely with poor aerosol delivery 1/1000) acutely with poor aerosol delivery

CorticosteroidsCorticosteroids• Suppresses underlying inflammation by blocking Suppresses underlying inflammation by blocking

proinflammation and activating antiinflammation proinflammation and activating antiinflammation at the level of gene transcriptionat the level of gene transcription

• Restores Restores 22 receptor function by reversing receptor function by reversing desensitization and downregulationdesensitization and downregulation

• Genetic polymorphism effects responseGenetic polymorphism effects response• Onset begins in 2-4 hours, peaks ~ 6-8 hrsOnset begins in 2-4 hours, peaks ~ 6-8 hrs• Dose = solumedrol 2 - 4 mg/kg/dayDose = solumedrol 2 - 4 mg/kg/day• Risk of myopathy, especially when also receiving Risk of myopathy, especially when also receiving

paralyticsparalytics

IpratropiumIpratropium• Anticholinergic quaternary derivative of Anticholinergic quaternary derivative of

atropineatropine

• Inhibits cholinergic-mediated Inhibits cholinergic-mediated bronchospasmbronchospasm

• Primarily effects larger bronchiPrimarily effects larger bronchi

• Use in conjunction with Use in conjunction with 2 2 bronchodilatorbronchodilator

• Most beneficial as multiple doses (250-Most beneficial as multiple doses (250-500500g Q20 min x3) in severe asthmag Q20 min x3) in severe asthma

TherapyTherapySecond-line therapySecond-line therapy Magnesium sulfateMagnesium sulfate HelioxHeliox rhDNAserhDNAse TheophyllineTheophylline

Intravenous Intravenous 2 2 catecholaminecatecholamine

Intravenous ketamineIntravenous ketamine

Magnesium sulfateMagnesium sulfate• Direct inhibition of Ca-mediated smooth Direct inhibition of Ca-mediated smooth

muscle constrictionmuscle constriction• Possibly useful to prevent hospitalization and Possibly useful to prevent hospitalization and

treat impending respiratory failuretreat impending respiratory failure• 25-75 mg/kg (max 2 gm) over 20 min 25-75 mg/kg (max 2 gm) over 20 min • Advantage is lack of cardiac stimulation Advantage is lack of cardiac stimulation

(tachycardia, (tachycardia, 0022 consumption) consumption)

• Side effects include nausea, vomiting, facial Side effects include nausea, vomiting, facial flushing, hypotension, muscle weaknessflushing, hypotension, muscle weakness

HelioxHeliox• Indication: treatment of increased airway resistance in areas of turbulent gas Indication: treatment of increased airway resistance in areas of turbulent gas

flow (density-dependent)flow (density-dependent)• Characteristics: decreased gas density, ideally requires 60-80% helium, no Characteristics: decreased gas density, ideally requires 60-80% helium, no

adverse effects, works adverse effects, works immediatelyimmediately• Goal: “therapeutic bridge”, changing the biophysical characteristics of gas flow Goal: “therapeutic bridge”, changing the biophysical characteristics of gas flow

until other treatments (e.g. steroids) take effect or until the disease improvesuntil other treatments (e.g. steroids) take effect or until the disease improves• Mechanisms:Mechanisms:

– with turbulent flow, heliox’s low gas density causes less airflow resistance and increased with turbulent flow, heliox’s low gas density causes less airflow resistance and increased flow rate (decreased work of breathing, decreased ventilatory pressures, less gas trapping) flow rate (decreased work of breathing, decreased ventilatory pressures, less gas trapping)

– low gas density decreases the Reynolds number, which shifts some flow from turbulent to low gas density decreases the Reynolds number, which shifts some flow from turbulent to laminar laminar

– low gas density increases the C0low gas density increases the C022 diffusion coefficient, improving C0 diffusion coefficient, improving C022 elimination elimination– low gas density facilitates the delivery of inhaled medications into the tracheobronchial treelow gas density facilitates the delivery of inhaled medications into the tracheobronchial tree

• Therapeutic targets: asthma, bronchiolitis, upper airway obstruction (e.g. croup, Therapeutic targets: asthma, bronchiolitis, upper airway obstruction (e.g. croup, postextubation stridor)postextubation stridor)

rhDNAserhDNAse• Recombinant Recombinant

deoxyribonucleasedeoxyribonuclease

• Decreases the sputum viscosity Decreases the sputum viscosity by degrading the extracellular by degrading the extracellular DNA released by neutrophils DNA released by neutrophils

Bronchial Cast

AminophyllineAminophylline• Phosphodiesterase inhibitor used to be first-line Phosphodiesterase inhibitor used to be first-line

therapytherapy• Relaxes airway smooth muscle, improves Relaxes airway smooth muscle, improves

diaphragm function, stimulates respiratory drive, diaphragm function, stimulates respiratory drive, increases catecholamine release, has increases catecholamine release, has antiinflammatory effectantiinflammatory effect

• Studies show uncertain beneficial effectsStudies show uncertain beneficial effects• Low therapeutic index- side effects include Low therapeutic index- side effects include

gastrointestinal (nausea, vomiting, abdominal gastrointestinal (nausea, vomiting, abdominal pain), neurologic (headache, agitation, seizures), pain), neurologic (headache, agitation, seizures), cardiovascular (arrhythmias, hypotension, cardiovascular (arrhythmias, hypotension, cardiac cardiac metabolic rate) metabolic rate)

Intravenous Intravenous 2 2 Catecholamine Catecholamine (terbutaline)(terbutaline)

• Direct systemic effect with increased Direct systemic effect with increased catecholamine side effects (load 10catecholamine side effects (load 10g/kg, max g/kg, max 0.4-1.0mg, followed by 0.1-4.00.4-1.0mg, followed by 0.1-4.0g/kg/min, max g/kg/min, max 1.0mg/hr)1.0mg/hr)

• Serious risks include hypotension, arrhythmias, Serious risks include hypotension, arrhythmias, tachycardia, ischemiatachycardia, ischemia

• Risks of intravenous terbutaline are much less Risks of intravenous terbutaline are much less than isoproterenolthan isoproterenol

• Maintain adequate cardiac output and blood Maintain adequate cardiac output and blood pressurepressure

Intravenous KetamineIntravenous Ketamine

• Dissociative anestheticDissociative anesthetic• Increases catecholaminesIncreases catecholamines• Direct airway smooth muscle relaxationDirect airway smooth muscle relaxation• Inhibits vagal toneInhibits vagal tone• 0.5-2.0mg/kg/hr0.5-2.0mg/kg/hr• Can be used as treatment with or without Can be used as treatment with or without

mechanical ventilationmechanical ventilation

Mechanical VentilationMechanical Ventilation• Avoid intubation if at all possible. Respiratory arrest is the only absolute indication Avoid intubation if at all possible. Respiratory arrest is the only absolute indication

(decide clinically, not from arterial blood gas).(decide clinically, not from arterial blood gas).• Consider a trial of Bipap, if tolerated, before intubationConsider a trial of Bipap, if tolerated, before intubation• Use ketamine (propofol also has bronchodilatory properties), paralysis, cuffed Use ketamine (propofol also has bronchodilatory properties), paralysis, cuffed

endotracheal tubeendotracheal tube• Fluid bolus prior to intubation to prevent decreased cardiac output (decreased Fluid bolus prior to intubation to prevent decreased cardiac output (decreased

venous return)venous return)• Basic principles are to give adequate ventilation without barotrauma and with Basic principles are to give adequate ventilation without barotrauma and with

minimal dynamic hyperinflationminimal dynamic hyperinflation– low minute ventilation (tidal volume, respiratory rate)low minute ventilation (tidal volume, respiratory rate)– prolonged expiratory time/shortened inspiratory time prolonged expiratory time/shortened inspiratory time – pressure-limited ventilation, limiting PIP to 35-40cmHpressure-limited ventilation, limiting PIP to 35-40cmH220, P0, Pplateauplateau 30cmH30cmH220, PEEP 0-0, PEEP 0-

5cmH5cmH2200– tolerate permissive hypercapnea (pHtolerate permissive hypercapnea (pH7.20)7.20)– sedation/paralysis (minimizes dysynchrony and C0sedation/paralysis (minimizes dysynchrony and C022 production) production)– monitor for dynamic hyperinflation/intrinsic PEEPmonitor for dynamic hyperinflation/intrinsic PEEP– consider extrinsic PEEP (<intrinsic PEEP)consider extrinsic PEEP (<intrinsic PEEP)