American Heart Association: 2005 Clinical American Heart Association: 2005 Clinical Guidelines for CPRGuidelines for CPR

TSRC meeting Lufkin Texas September 14, 2007TSRC meeting Lufkin Texas September 14, 2007Management of Near-Fatal AsthmaManagement of Near-Fatal Asthma

By By Elizabeth Kelley Buzbee AAS, RRT-NPS, Elizabeth Kelley Buzbee AAS, RRT-NPS,

RCPRCPKingwood College Respiratory Care Kingwood College Respiratory Care

facultyfaculty

►Severe asthma accounts for 2%-20% Severe asthma accounts for 2%-20% of all ICU admissions and up to 1/3rd of all ICU admissions and up to 1/3rd of these patients require intubation of these patients require intubation and mechanical ventilation. [AHI pp. and mechanical ventilation. [AHI pp. 139]139]

Pathophysiology per NIH 1996 Pathophysiology per NIH 1996 clinical guidelinesclinical guidelines

► Asthma… [is a ].. chronic inflammatory disorder of Asthma… [is a ].. chronic inflammatory disorder of the airways. the airways.

► Features of asthma include:Features of asthma include:— — Denudation of airway epitheliumDenudation of airway epithelium— — Collagen deposition beneath basement membraneCollagen deposition beneath basement membrane— — EdemaEdema— — Mast cell activationMast cell activation— — Inflammatory cell infiltrationInflammatory cell infiltration– – Neutrophils (especially in sudden-onset, fatal Neutrophils (especially in sudden-onset, fatal

asthma exacerbations)asthma exacerbations)– – EosinophilsEosinophils– – LymphocytesLymphocytes (TH2-like cells) (TH2-like cells)

►Atopy, the genetic predisposition for Atopy, the genetic predisposition for the development of an IgE-mediated the development of an IgE-mediated response to common inhaled allergens response to common inhaled allergens is the strongest identifiable is the strongest identifiable predisposing factor for developing predisposing factor for developing asthma.asthma.

►Airway inflammation also contributes Airway inflammation also contributes to several forms of airflow limitation, to several forms of airflow limitation, including acute bronchospasm, airway including acute bronchospasm, airway edema, mucus plug formation, and edema, mucus plug formation, and airway wall remodeling.airway wall remodeling.

►This last problem is thought to This last problem is thought to

contribute to the difficulty in breaking contribute to the difficulty in breaking some asthmaticssome asthmatics

Differential diagnosisDifferential diagnosis includes:includes:

►pulmonary edema, COPD, anaphylaxis, pulmonary edema, COPD, anaphylaxis, foreign body aspiration, pulmonary foreign body aspiration, pulmonary embolism, bronchiectasis and embolism, bronchiectasis and subglottic mass. [AHI pp. 139]subglottic mass. [AHI pp. 139]

Clinical signs & symptoms of Clinical signs & symptoms of severe asthma per the NIH:severe asthma per the NIH:

►While the primary clinical sign of While the primary clinical sign of asthma is expiratory wheezing and asthma is expiratory wheezing and coughing, it is important to understand coughing, it is important to understand that not all asthmatics wheeze and that not all asthmatics wheeze and that severe airway compromise may that severe airway compromise may be expressed as poor air movement.be expressed as poor air movement.

History of any of the History of any of the following:following:

►Cough, worse particularly at nightCough, worse particularly at night►Recurrent wheezeRecurrent wheeze►Recurrent difficulty in breathingRecurrent difficulty in breathing►Recurrent chest tightnessRecurrent chest tightness►May have family history of atopic May have family history of atopic

diseases or asthmadiseases or asthma

►Reversible airflow limitation and Reversible airflow limitation and diurnal variation as measured by diurnal variation as measured by using a peak flow meter, for using a peak flow meter, for example:example:

►— — Peak expiratory flow (PEF) varies Peak expiratory flow (PEF) varies 20% or more from PEF measurement 20% or more from PEF measurement on arising in the morning (before on arising in the morning (before taking an inhaled short-acting beta2-taking an inhaled short-acting beta2-agonist) to PEF measurement in the agonist) to PEF measurement in the early afternoon (after taking an early afternoon (after taking an inhaled short-acting beta2-agonist).inhaled short-acting beta2-agonist).

SeveritySeverity

► ► For the purpose of treatment, asthmatics are For the purpose of treatment, asthmatics are

classified as [1] classified as [1] mild intermittentmild intermittent, [2] , [2] mild mild persistantpersistant, [3] , [3] moderate persistantmoderate persistant, and , and [4] [4] severe persistant. severe persistant.

► It is important to understand that near-fatal It is important to understand that near-fatal asthma exacerbation can happen to asthma exacerbation can happen to anyany patient at patient at anyany level of severity. level of severity.

► Obviously, a person with severe persistant Obviously, a person with severe persistant asthma is at increased risk of fatal asthma asthma is at increased risk of fatal asthma exacerbation, but the person in mild exacerbation, but the person in mild intermittent asthma is not immune to severe intermittent asthma is not immune to severe exacerbations. [NIH]exacerbations. [NIH]

Treatment:Treatment:

►Initial stabilizationInitial stabilization includes includes aggressive treatment with aggressive treatment with supplementary 02, inhaled short-supplementary 02, inhaled short-acting bronchodilators & systemic acting bronchodilators & systemic steroids.steroids.

►Supplementary 02: Supplementary 02: titrate to keep titrate to keep Sp02 above 92%. Sp02 above 92%.

TX continuedTX continued

► Inhaled short-acting Beta2 bronchodilators: Inhaled short-acting Beta2 bronchodilators: studies have shown no clear advantage to SVN over MDI, studies have shown no clear advantage to SVN over MDI,

but patients in severe distress have trouble operating MDIbut patients in severe distress have trouble operating MDI 2.5 to 5 mg albuterol sulfate Q 15-20 minutes 2.5 to 5 mg albuterol sulfate Q 15-20 minutes

intermittentlyintermittently 10 to 15 mg/hour by continuous nebulization10 to 15 mg/hour by continuous nebulization No clear benefit to levalbuterol [Xopenex TM]No clear benefit to levalbuterol [Xopenex TM]

► Systemic steroids.Systemic steroids. Onset of action of steroids by any route is 6-12 hoursOnset of action of steroids by any route is 6-12 hours Decreases the inflammation associated with asthmatic Decreases the inflammation associated with asthmatic

exacerbationexacerbation Initial adult dose of methylprednisolone is 125 mg.Initial adult dose of methylprednisolone is 125 mg. Systemic steroids better than inhaled steroid for the acute Systemic steroids better than inhaled steroid for the acute

exacerbationexacerbation

Subcutaneous epinephrine/ Subcutaneous epinephrine/ or terbutalineor terbutaline

► Subcutaneous epinephrine [1:1000] .01 mg/kg Subcutaneous epinephrine [1:1000] .01 mg/kg divided into three dosesdivided into three doses

oror► .25 mg subcutaneous terbutaline has prolonged .25 mg subcutaneous terbutaline has prolonged

onset of actiononset of action► Of these two methods, subcutaneous epinephrine is Of these two methods, subcutaneous epinephrine is

preferred when the patient is in anaphylactic shock preferred when the patient is in anaphylactic shock because of the alpha and Beta1 effects of the drug, because of the alpha and Beta1 effects of the drug,

► while terbutaline is a specific beta2 agonist with while terbutaline is a specific beta2 agonist with longer duration of action.longer duration of action.

Additional treatments [after initial Additional treatments [after initial stabilization is started]stabilization is started]

► Cholinergic blockersCholinergic blockers such as . 5mg of such as . 5mg of Atrovent may give improvement over Albuterol Atrovent may give improvement over Albuterol alone, but it has a slow onset of action [20 alone, but it has a slow onset of action [20 minutes.]minutes.]

► New longer-acting cholinergic blockers such as New longer-acting cholinergic blockers such as Tiotropium [Spiriva DPI] are being studied for Tiotropium [Spiriva DPI] are being studied for asthma. asthma. Remember! DPI may be difficult for Remember! DPI may be difficult for persons in distress to trigger.persons in distress to trigger.

►While not all asthmatic react favorable to the While not all asthmatic react favorable to the addition of cholinergic blockers, elder persons addition of cholinergic blockers, elder persons who are intolerant to Beta2 drugs and those who are intolerant to Beta2 drugs and those with nocturnal symptoms might do well with with nocturnal symptoms might do well with these drugs. [Respiratory Care Vol 52, # 7 pp. these drugs. [Respiratory Care Vol 52, # 7 pp. 840]840]

Magnesium SulfateMagnesium Sulfate

► Mg by IV works well with Beta2 agonists & Mg by IV works well with Beta2 agonists & steroids. Dose is 1.2 to 2 grams over 20 steroids. Dose is 1.2 to 2 grams over 20 minutes.minutes.

► It is known that acute temporary elevation of It is known that acute temporary elevation of serum magnesium can result in bronchodilation serum magnesium can result in bronchodilation even in patients with normal magnesium levels. even in patients with normal magnesium levels.

► Evidence also shows that magnesium acts as a Evidence also shows that magnesium acts as a competitive antagonist with calcium and competitive antagonist with calcium and reduces the neutrophilic burst associated with reduces the neutrophilic burst associated with the inflammatory response in asthma.the inflammatory response in asthma.

Hazards of magnesium Hazards of magnesium

►When given by IV to slow down labor, When given by IV to slow down labor, women have been known to go into women have been known to go into pulmonary edema, and one study of pulmonary edema, and one study of asthmatics found that combining asthmatics found that combining magnesium sulfate and terbutaline magnesium sulfate and terbutaline increased terbutaline's cardiovascular side increased terbutaline's cardiovascular side effects (Chest, 1994, Vol. 105, pp. 701-705). effects (Chest, 1994, Vol. 105, pp. 701-705).

►Magnesium sulfate can decrease muscle Magnesium sulfate can decrease muscle strength –even to the point of respiratory strength –even to the point of respiratory failure due to paralysis.failure due to paralysis.

XanthinesXanthines

► such as aminophyline/ theophylline have such as aminophyline/ theophylline have such dangerous side effects [cardiac such dangerous side effects [cardiac arrhythmias and seizures] that they are arrhythmias and seizures] that they are infrequently used for asthma. infrequently used for asthma.

► Aminophyline works by inhibiting Aminophyline works by inhibiting phosphodiesterase, an enzyme that breaks phosphodiesterase, an enzyme that breaks down C-AMP. If C-AMP is prolonged, down C-AMP. If C-AMP is prolonged, bronchodilation is prolonged. The bronchodilation is prolonged. The therapeutic serum level of theophylline is 5-therapeutic serum level of theophylline is 5-15 micrograms for asthma control.15 micrograms for asthma control.

KetamineKetamine

► is an anesthetic that seems to have is an anesthetic that seems to have bronchodilator properties, but it also bronchodilator properties, but it also stimulates copious secretions. stimulates copious secretions. Research is limited and this drug’s Research is limited and this drug’s affect on asthma is unclear right now.affect on asthma is unclear right now.

Heliox:Heliox:

►deposition of Beta2 drugs by SVN is deposition of Beta2 drugs by SVN is improved with the low density helium improved with the low density helium gas mixed with 02 in 70:30 ratio, but gas mixed with 02 in 70:30 ratio, but research has not supported the use of research has not supported the use of heliox for acute asthma unless the heliox for acute asthma unless the patient is not responding to patient is not responding to conventional care.conventional care.

► If the patient needs more than Fi02 If the patient needs more than Fi02 30%, heliox is useless.30%, heliox is useless.

Inhaled general Inhaled general anestheticsanesthetics

►have been used to treat persons with have been used to treat persons with status asthmaticus who are resistant status asthmaticus who are resistant to maximal conventional care. These to maximal conventional care. These drugs may enhance patient-ventilator drugs may enhance patient-ventilator synchrony This technique involves the synchrony This technique involves the ICU setting. There are no randomized ICU setting. There are no randomized studies.studies.

Leukotriene blockersLeukotriene blockers

►have not been studied during acute have not been studied during acute attacks, but works well as maintenance attacks, but works well as maintenance drugs. drugs.

►Leukotrienes created by the arachidonic Leukotrienes created by the arachidonic acids were once called the “slow reacting acids were once called the “slow reacting substance of anaphylaxis” and is substance of anaphylaxis” and is responsible for bronchospasm, responsible for bronchospasm, vasodilation, increased capillary vasodilation, increased capillary permeability, increased mucus production permeability, increased mucus production and decreased mucociliary clearance. and decreased mucociliary clearance. (Colbert & Mason pp. 137 )(Colbert & Mason pp. 137 )

AHI 2005 guidelines regarding Mechanical AHI 2005 guidelines regarding Mechanical ventilation in the acute asthmatic exacerbationventilation in the acute asthmatic exacerbation

►NIPPV with BiPap might work with the NIPPV with BiPap might work with the asthmatic who can still protect his airway asthmatic who can still protect his airway and who has an adequate ventilatory drive.and who has an adequate ventilatory drive.

► Endotracheal intubation & mechanical Endotracheal intubation & mechanical ventilation is a challenge. Mechanical ventilation is a challenge. Mechanical ventilation is complicated by air-trapping ventilation is complicated by air-trapping that can lead to air leaks-- even that can lead to air leaks-- even pneumothoraxpneumothorax RATERATE: 6- 10 bpm: 6- 10 bpm VTVT: 6-8 ml/kg: 6-8 ml/kg I:EI:E 1:4 or 1:5 1:4 or 1:5 Flow rateFlow rate 80-100 LPM to decrease the Ti 80-100 LPM to decrease the Ti

►Permissive hypercapneaPermissive hypercapnea can be can be used to keep airway pressure down and used to keep airway pressure down and minimize barotrauma.minimize barotrauma.

► If If auto-PEEP is still an issueauto-PEEP is still an issue, , consider decreasing the VT to 3 to 5 consider decreasing the VT to 3 to 5 ml/kg and the rate by 2 bpmml/kg and the rate by 2 bpm

►Remember that removal of the circuit Remember that removal of the circuit from the ventilator will vent off excess from the ventilator will vent off excess gases in the tube caused by air-gases in the tube caused by air-trapping.trapping.

Watch for these complications:Watch for these complications:

► Tube displacementTube displacement. Intubate with the largest . Intubate with the largest tube available and monitor it for placement with tube available and monitor it for placement with bilateral breath sounds and serial Sp02.bilateral breath sounds and serial Sp02.

► Tube obstructionTube obstruction: never forget that asthmatics do : never forget that asthmatics do suffer from thick secretions and may require suffer from thick secretions and may require assessment of the airway and frequent suctioning.assessment of the airway and frequent suctioning.

► Sudden deteriorationSudden deterioration may be seen with a may be seen with a pneumothorax. Remember that small pneumothorax. Remember that small pneumothorax will, in the presence of positive pneumothorax will, in the presence of positive pressure, become a tension pneumothorax. Rapid pressure, become a tension pneumothorax. Rapid decompression by needle aspiration or chest tube decompression by needle aspiration or chest tube placement may be needed.placement may be needed.

Recent research in asthma Recent research in asthma [[Respiratory Care Vol 52 #7 July 2007Respiratory Care Vol 52 #7 July 2007]]

►Hazards of continuous inhaled Hazards of continuous inhaled Beta2Beta2

►During continuous short-acting Beta2 During continuous short-acting Beta2 agonists doses of more than agonists doses of more than .4mg/kg/hour were associated with .4mg/kg/hour were associated with significant drops in serum potassium significant drops in serum potassium which can increase the HR. [pp.823] which can increase the HR. [pp.823]

How the Beta2 receptors are triggeredHow the Beta2 receptors are triggered

Hazards of long-acting Hazards of long-acting inhaled Beta2inhaled Beta2

►Long-acting bronchodilators such as Long-acting bronchodilators such as salmeterol are associated with salmeterol are associated with increased deaths from asthma increased deaths from asthma particularly if particularly if given without steroidsgiven without steroids. . [pp 826-827.] Worldwide, salmeterol [pp 826-827.] Worldwide, salmeterol may be responsible for 4-5k deaths may be responsible for 4-5k deaths

► In a huge study of 26k patients in 6k In a huge study of 26k patients in 6k sites, not only was a slight, but sites, not only was a slight, but clinically significant increase in deaths clinically significant increase in deaths associated with LABD. The large associated with LABD. The large number of African American deaths number of African American deaths resulting during this research caused resulting during this research caused the project to be stopped. [pp. 286] the project to be stopped. [pp. 286]

► It is not known if there was a It is not known if there was a difference in these patients’ difference in these patients’ underlying asthma condition or in their underlying asthma condition or in their compliance. More studies need to be compliance. More studies need to be done.done.

Racemic albuterolRacemic albuterol

► There is some concern about racemic Beta2 There is some concern about racemic Beta2 bronchodilators such as albuterol. bronchodilators such as albuterol.

► The R isomer is associated with The R isomer is associated with bronchodilation while the S isomer may bronchodilation while the S isomer may actually actually causecause bronchospasm. bronchospasm.

►Drugs such as levalbuterol are specific R Drugs such as levalbuterol are specific R isomer beta2 bronchodilators.isomer beta2 bronchodilators.

►we know that the S isomer is not inert and we know that the S isomer is not inert and currently the FDA will not ok any more currently the FDA will not ok any more racemic beta2 bronchodilators until the racemic beta2 bronchodilators until the isomers are both tested for safetyisomers are both tested for safety

Per RC July 2007: Recent research on the Per RC July 2007: Recent research on the racemic Beta2 problem:racemic Beta2 problem:

► while the S isomer caused problems in vitro, while the S isomer caused problems in vitro, this has not be duplicated in vivo [pp. 824]this has not be duplicated in vivo [pp. 824]

► when compared, the racemic albuterol and the S when compared, the racemic albuterol and the S albuterol both showed protection against albuterol both showed protection against methacholine challengemethacholine challenge

► during a single dose test, there was no difference in during a single dose test, there was no difference in bronchodilation nor in occurrence of adverse side bronchodilation nor in occurrence of adverse side effects between racemic and R albuterol effects between racemic and R albuterol [levalbuterol] [levalbuterol]

► there was no problems found with racemic there was no problems found with racemic albuterol during adenosine challengealbuterol during adenosine challenge

► there was no difference in hospital stays between there was no difference in hospital stays between racemic albuterol and levalbuterolracemic albuterol and levalbuterol

Persons who Persons who mightmight be at increased risk be at increased risk for side effects of racemic beta2 for side effects of racemic beta2

bronchodilators bronchodilators

► There are at least 9 genetic differences in Beta2 There are at least 9 genetic differences in Beta2 receptors. [polymorphism] receptors. [polymorphism]

► One of them [One of them [the arginine/ arginine polymorphismthe arginine/ arginine polymorphism] ] found at the 16th amino-acid chain seems to be found at the 16th amino-acid chain seems to be associated with impaired bronchodilation with associated with impaired bronchodilation with racemic beta2 bronchodilators. racemic beta2 bronchodilators.

► In other words, these folks may have problems with In other words, these folks may have problems with the S isomer of albuterol and more research needs the S isomer of albuterol and more research needs to be done. [pp. 824]to be done. [pp. 824]

► 1/6th of all USA asthmatics have this genetic 1/6th of all USA asthmatics have this genetic problem—but 25% of African Americans have this problem—but 25% of African Americans have this particular polymorphism. [pp. 824.]particular polymorphism. [pp. 824.]

► RoflumilastRoflumilast, a phosphodiesterase 4 inhibitor is , a phosphodiesterase 4 inhibitor is showing promising results with limiting exercised-showing promising results with limiting exercised-induced drops in FEV1 with patients with asthma. induced drops in FEV1 with patients with asthma. Will it be as effective as xanthines without the side Will it be as effective as xanthines without the side effects?effects?

► HomecareHomecare► A recent survey of New York City area pulmonary A recent survey of New York City area pulmonary

physicians found that 71% presented their physicians found that 71% presented their asthmatic patients with written treatment plans.asthmatic patients with written treatment plans.

► Links:Links:►

http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm