Therapies For Severe Asthma
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Transcript of Therapies For Severe Asthma
Therapies for Severe Asthma
Joan Roberts, M.D.
Assistant Professor
Pediatric Critical Care Medicine
University of Washington
Asthma is More Prevalent
Asthma is the most common disease of childhood
Affects 9% of kids (groups 15-20%) 10 million missed days of school 3 million office visits (1995, < 15 year
olds) 570,000 ED visits (1995, < 15 year olds)
Is Asthma More Severe? Hospitalization rates till mid 90’s Death- rates for all ages
– 2.1/1,000,000 kids < 5 years– 3.7/1,000,000 kids 5-14 years– 2/10,000 hospital kids (California)– 4/1000 PICU kids
Intubation rates in mid 80’s - 90’s (0.25 - 0.6 of hospital admits for
children with asthma– (large range) mean 16% of PICU admits
Asthma Death
Half at home Some unpredictable Risk factors
– poor compliance, hx severe disease, poverty/Medicaid insurance
– twice as common in African Americans– psychological problems
Established Therapies for Asthma Exacerbation Oxygen Steroids Beta agonists Anticholinergics
Steroids for an “Inflammatory” Disease Systemic steroids for all hospitalized pts equally effective IV vs PO some effect in several hrs, peak 9-12
hrs recommended dose is 1 mg/kg per dose
q 4-6 hours of methylpred or prednisone
Mechanism of Action Multiple effects: Am J Resp Crit Care 1996; 154: S21-
27, Barnes production of: interleukins, TNF alpha,
GMCSF, RANTES and others breakdown of IL-2 iNO synthase, cyclo-oxygenase,
phospholipase A2
protease inhibitors, β-2 receptors cellular immune function & mucus formation
Steroid Therapy t1/2 of prednisone 2-4 hours regimens < 5 days - stop w/o taper inhaled fluticasone 2mg not adequate
for ED visits (N Engl J Med 2000; 343: 689 by Schuh et al)
inhaled budesonide (1600 μgm/day) for 21 days after admit relapse (JAMA 1999; 281: 2119-2126, by Rowe et al)
Beta agonists
Most used and effective bronchodilators actives adenyl cyclase cAMP cAMP activates protein kinase leading
to smooth muscle relaxation available po, inhaled, sub Q and IV
Inhaled β agonists
Greater bronchial dilatation systemic effects
All dosed to effect When to give continuous not crystal
clear Continuous cheaper, associated with
faster improvement & LOS
Delivery of Inhaled Medication
Affected by particle size & shape, pt breathing factors and airway caliber
particle size (1-5 μm ideal) Jet nebulizers - (average particle 1.5-6
μm) (1-5% inhaled) MDI’s - powder and a liquid propellant
(15 m/sec) (7-14 % inhaled)
MDI vs Nebs
ED & hospital asthma- MDI’s- cost and same to slightly LOS (Arch Dis Child 1999; 80: 421-423, Dewar et al)
MDI’s hard to give continuously If intubated MDI’s have better drug
delivery (3-4% with 6.5 ETT vs < 1% neb)
Continuous Albuterol
Recommended doses 0.5 mg/kg/hr or 10-60 mg/hr
toxicity- hypokalemia, agitation, tremulousness, tachycardia, ventricular dysrhythmias, hypoxia- HPV
dosed to effect
IV Terbutaline
No studies to support over inhaled tx Can ensure delivery if obstructed or
intubated Dose 10 μg/kg IV load over 5-10 min infusion 0.4-4 μg/kg/min Rebolus with increased doses 2-5
mcg/kg
Terbutaline Toxicity
Dysrhythmias Increased myocardial O2 consumption Myocardial ischemia Hypokalemia Past history with isuprel Chiang et al. J Pediatrics 2000; 137: 73-7
(29 patients)
Toxicity
28 children with severe asthma on continuous nebs
19 (66%) had possible ischemic changes on EKG before terbutaline
80% of children on terb had NSST changes
17/28 had CPK, 3/28 had CPK MB 0/28 had significantly troponin
Terbutaline Dosing
No studies to guide us IV + inhaled? IV alone? If using ventilator- IV administration
reliable
Anticholinergics
Ipatropium- quarternary amino acid blocks cholinergic bronchoconstriction
About 10% improvement in PEF over albuterol alone
Three repeat doses in ED- admission and PEF. Schuh et al (250 μgm/dose,J Pediatr 1995; 126: 639-45)
dosed q 6 hours after admission
Other Non-Established Therapies
Theophylline Magnesium sulfate Heliox Volatile agents ECLS
Theophylline
Still recommended as a second line agent for asthma
Mechanism of action: nonselective III and IV PDE inhibitor- cAMP & cGMP
immunomodulatory, anti-inflammatory and bronchoprotective effects
toxicity in overdose
Theophylline for Status Asthmaticus No studies in US that suggest additional
benefit over inhaled β-agents + steroids Yung and South (Arch Dis Child 1998; 79: 405-
410) studies 163 kids 0/81 Aminophylline patients intubated
compared to 5/82 2/3’s had nausea and vomiting
Magnesium Sulfate
Decreases free Ca++- smooth muscle relaxation, may stabilize Mast cells and histamine release
No definitive studies Bloch et al (Chest 1995; 107: 1576-81)
– 67 adults 2 gm MgSO4
– subset of severe FEV1 (< 25%) had admission rates
Magnesium Sulfate
Pediatric dose 25-100 mg/kg over 20 minutes
Target serum level 3.5- 4.5 mg/dL Believers speculate a dose response
relationship is present May or may not work- but nontoxic
Helium + Oxygen = Heliox
Helium- inert low MW gas, insoluble at 1 ATM
low density (0.179 μ poise) vs. air (1.293) and O2 (1.429)
density- turbulent flow increases laminar and turbulent
– P = k1 (laminar flow) + k2 (turbulent flow)2
– k2 α density
Heliox
Discovered in 1895 1934 used for airway obstruction (Barach) Limited use if pt needs O2
Try to deliver at least 60% helium, ideally 80%
20/80 = 0.429, 40/60 = 0.678 & 80/20 = 1.178 μ poise
Heliox
Established therapies Post extubation stridor RCT Kemper et
al (Crit Care Med 1991; 19: 356-9)
Heliox improves delivery of nebulized meds. Anderson et al (Am Rev Respir Dis 1993; 147: 524-528)
Heliox Case series of severe asthmatics
– showed paCO2 and pH.
Pt served as control- pulsus paradoxus & FEV1
Non intubated patients- Randomized studies– studies 11-18 subjects each
– some show pulsus paradoxus & PEF or FEV1 and others did not.
Heliox and Ventilation
Many ventilators not calibrated for Helium and underestimate TV.
Case series of Heliox via ventilator– heliox use- paO2, pH while paCO2 and
peak pressures on the ventilator
Volatile Agents
Halogenated anesthetic gases relax smooth muscle & antagonize acetyl choline and histamine mediated constriction
Case reports for use in life-threatening status asthmatics
Problems with waste gas Can use Siemens 900 C ventilator
Extracorporeal Life Support
Both VV and VA ECMO have been used for life threatening
ELSO registry in 1997 had 27 cases of asthma
88% survival
Mechanical Ventilation
Indications - profound hypoxemia, life-threatening respiratory muscle fatigue or altered mental status
What does that mean? NIH recommends intubation for paCO2
over 42 torr
Mechanical Ventilation
Historically associated with increased risk of death.
Problematic- patients have severe airway obstruction and develop air trapping, pneumothorax & bronchopleural fistula.
Limits delivery of inhaled meds.
Mechanical Ventilation Strategy of permissive hypercapnia Prevent hypoxia Provide long E time Normal I time Infrequent breaths Limit airway pressure (small TV) Mortality Stein 1980’s (8% PICU now
0.4%)
Controlled Ventilation
Use low respiratory rates to increase expiratory time - avoid air trapping.
Heavily sedated +/- muscle relaxed. Full ventilatory support.
Risk of steroid and NMBA myopathies
Controlled Ventilation
Ventilate till anti-inflammatory and bronchodilators have decreased airway obstruction and airway pressures.
Extubate deeply sedated.
Support Mode Ventilation
Wetzel (Crit Care Med 1996; 24: 1603-1605)
Use either PS or VS Patient determines respiratory rate,
inspiratory time and can increase tidal volume
Results in lower airway pressures, improved patient comfort
Avoids NMBD
Support Ventilation
Only studied in case series paCO2 and pH Proposed mechanism: pt’s accessory
muscles augment exhalation
Clinical PICU Practice
14 PICUs with 1631 asthmatics 16% received mechanical ventilation Centers use of ventilation varied from 0-
47% When grouped into 20% or > 20% use of
ventilation, Groups did not vary by PRISM III score, pH, paO2, paCO2 or respiratory rates.
PICU Clinical Practice
Study limitations:– grouping arbitrary 2/3 vs 1/3, also done with
25% and 30% cuts- similar results– gases obtained on 40% of pts– no information on use of
• continuous neb /dose• IV terbutaline• heliox
• MgSO4
NonVentilation among “High” & “Low” Use Centers “Low” N=1041 PRISM III 2.2 (3.2) paCO2 40 (17) days PICU 1 (1,2)* days hosp 3 (2,5)* aline 7%, CVC .3%* Worst gases
– 50-60 torr 8%– 60-80 torr 2%– > 80 torr 2%
“High” N=332 PRISM III 2.3 (2.8) paCO2 41 (9) days PICU 2 (1,2) Days in hosp 4 (3,6) aline 15%, CVC 3% Worst gases
– 50-60 torr 11%– 60-80 torr 4%– > 80 torr 0%
Ventilation among “High” & “Low” Use Centers < “low” Pts N=133 PRISM III 6 (3,10) paCO2 67 (28)* a line 65%* CVC 25%* Days PICU 3 (1,6)* Days Vent 2 (1,5)* Days Hosp 6 (4,10)*
“high” Pts N=125 PRISM III 6 (3,9) paCO2 59 (21) a lines 79% CVC 68% Days PICU 4 (2,8) Days Vent 3 (2,6) Days Hosp 8(4.5,13)
High vs Low Ventilation Centers
After adjustment for age, paCO2 and PRISM III scores: “high” use center - independent risk factor for PICU and Hospital LOS for ventilated & non ventilated asthmatics
Among ventilated pts - “high” use was an independent risk factor for length of ventilation
Severity of Asthma Exacerbation
Mild Mod SevereBreathless w/ walking w/talking at rest
talks sentences phrases words
Accessorymuscles use
usually not commonly usually
Pulsusparadox
< 10 mm Hg 10-20 mm Hg > 20 mm Hg
PEF 80% 50-80% < 50%
Sat on RA
PaCO2
> 95%
< 42 torr
91-95%
< 42 torr
< 91%
> 42 torr
Management Mild-Moderate Asthma Exacerbation PEF > 50% Oxygen sats > 90%, repeated inhaled -
2 agonist, systemic steroids Reassess PEF 50-80%, treat 1-3 hrs If PEF > 70% 1 hr after tx- Discharge
– with written plan
– course of steroids
– close medical follow
– education
Management Moderate Asthma Exacerbation PEF < 50% Oxygen sats > 90%, repeated inhaled β-
2 agonist & anti-cholinergics, systemic steroids
Reassess PEF 50-70%, Admit ward Oxygen sats > 90%, repeated inhaled β-
2 agonist q 1-3 hours & inhaled anti-cholinergics, systemic steroids
Management of Severe Asthma Exacerbation PEF < 50% Oxygen sats > 90%, repeated inhaled
ß-2 agonist & anti-cholinergics, systemic steroids
Reassess PEF < 50% admit PICU Oxygen sats > 90%, continuous inhaled
ß-2 agonist & inhaled anti- cholinergics, systemic steroids
Near or Impending Respiratory Failure Oxygen > 90% (goal) IV steroids Continuous ß-2 agonist inhaled Repeated anti-cholinergics inhaled Move to ICU Monitor closely- intubation
My Treatment for Severe Asthma
Systemic steroids (1-2mg/kg/dose q6) Albuterol (10mg) + ipatroprium X three Move to PICU if in extremus Continuous Albuterol escalating each
hour up to straight drug if not improving. If not improving, consider IV terbutaline
and or Heliox
My Treatment for Severe Asthma
If still clinically in marked distress Blood gases worsening Try MgSO4
Escalate terbutaline and monitor to intubate if obtunded or hypoxemic
If intubating expect problems
My Treatment for Severe Asthma
Intubate with ketamine, rocuronium, lidocaine
Sedative infusion Handbag pt to determine initial rate and
pressure limits Allow spontaneous ventilation Volume support or pressure support
mode
My Treatment for Severe Asthma
Extubate when paCO2 normal on minimal vent setting VS 5 cc/kg or PS 10 and dyspnea only slight and off heliox.
Extubate to continuous nebs. Wean terbutaline Then nebs Consult pulmonary for better home
routine!
Clinical Asthma Patterns
Infrequent Episodic Asthma (75%)- wheezes < 1/4-6 wks, minor wheezing - heavy exertion, no interval symptoms, nl lung function
Frequent Episodic Asthma (20%)- wheezes <1/wk, wheezes - moderate exercise but prevented
with β-2 agonist. Prophylactic tx usually needed
Persistent Asthma (5%) need β-2 agonist > 3/wk, frequent night awakening, chest tightness wheezes with minor exercise. Prophylactic tx mandatory