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1 대한내과학회지 : 제 73 권부록 2 호 2007 임상강좌 E xacerbation of Asthm a 성균관대학교의과대학내과학교실 최동철 Key Points -천식의악화란호흡곤란, 기침, 천명, 흉부압박감등의증상중한가지이상이나타나는것을가리킨다. -천식이악화되면숨을내쉬기어려워지고폐기능검사에서최대호기유속이나 1초간노력성호기량이감소한다. -주요한치료는기관지확장제, 스테로이드및산소투여이다. -치료목표는환기장애와저산소증을개선하고재발을방지하는것이다. -심한천식발작은응급상황이며적절한시설이있는곳에서치료해야하고전문가의감독이필요하다. -가벼운천식발작( 최대호기유속의감소가 20% 미만 ) 은지역의료기관에서치료할수있다 Allergens Exercise Inducers Respiratory viral infections Asthma flare Irritants Provokers Occupational agents Aspirin Respiratory viral infections Trends in Prevalence of Asthma By Age, U.S., Rate/1,000 Persons Age (years) < Total (All Ages) Rate/100,000 Persons 5 Black Female Death Rates for Asthma By Race, Sex, U.S., Black Male White Female 30 1 White Male Year Year - S 737 -

2 - 대한내과학회지 : 제 73 권부록 2 호 Histrory (1) Q1: 환자의호흡곤란이천식발작인가? A. Timing of dyspnea Acute onset anxiety, hyperventilation asthma, pulmonary edema pulmonary embolism, chest trauma (pneumothorax, rib fracture, contusion) spontaneous pneumothorax Insiduous onset COPD interstitial fibrosis sarcoidosis diseases of chest wall or diaphragm Histrory (2) Histrory (3) Nocturnal dyspnea Asthma, CHF, GE reflux Orthopnea CHF, massive ascites or pregnancy Bilateral phrenic nerve paralysis, severe COPD Platypnea(Difficulty in breathing when erect, relieved by lying down) AV malformation in lung, interatrial shunt Trepopnea(dyspnoea in one lateral position) Heart disease, VQ mismatch B. Relationship to physical activity ATS Shortness of Breath scale Grade 0 (none) Not troubled by shortness of breath when hurrying on the level or walking up a slight hill Grade 1 (mild) Troubled by shortness of breath when hurrying on the level or walking up a slight hill Grade 2 (moderate) Walks slower than the people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace in the level Grade 3 (severe) Stops for breath after walking about 100 yards or after a fewminutes on the level Grade 4 (very severe) Too breathlessness to leave the house, or breathless on dressing or undressing Histrory (4) Physical Exam (1) High Risk patients -기도삽관및인공호흡기사용의병력 - 지난해에천식발작으로응급실을방문하거나입원하였던환자 - 최근에경구스테로이드를사용하였거나사용중인환자 - 흡입스테로이드를규칙적으로사용하지않는환자 -흡입기관지확장제를한달에1개이상사용하는환자 - 천식치료계획에순응도가낮은환자 - 치료의시작과동시에문진및진찰을실시한다. - 관찰할사항 : 말을잘하나? 호흡및맥박수, 보조호흡근의사용, 비정상적인호흡음 - 진찰만으로는천식발작및저산소증의중증도를객관적으로평가할수없음 - 폐기능의측정이매우중요 - 치료에지장이없도록신속히폐기능을측정하고치료를시작한다. - S 738 -

3 - 최동철 : - Physical Exam (2) Inspection, Percussion, Palpation Physical Exam (3) Mechanism of production of wheezing - Vital signs including respiration rate - Body habitus: obese or cachectic - Position: leaning foward in COPD - Expansion of chest wall: symmetricity - Use of accessory muscles: ICS or suprclavicular fossa retraction - Cyanosis or clubbing - Extended jugular vein or hepatojugular reflux - Unilateral vs bilateral L/E edema 1. Normal airway 2. Slight narrowing alternation of 2 & 3 produces continuous sound 3. Greater narrowing Labaratory test (1) Screening tests in dypnea (1) Labaratory test (2) Screening tests in dypnea (2) General Principle " The labaratory test is occasionally of help in the diagnosis of dyspnea" (StulbargMS, Adams L: Dyspnea. In Textbook of respiartorydiseases p521) Screening tests to be performed Most helpful : Chest PA, ECG, Spirometry, ABGA Occasionally helpful: CBC, TFT* * variable depending on authors A. Plain chest radiography - diagnosis: pneumothorax, pleural effusion, pneumonia, TB, emphysema, lung cancer, interstitial lung disease - helpful: cardiomegaly, chest wall deformity, pulmonary vascular abnormality - In asthma: hyperinflation, pneumothorax B. 12 lead ECG - does not establish diagnosis directly - provides indirect evidence for causative diseases of dyspnea (arrhythmia, myocardial ischemia, chamber enlargement etc) Labaratory test (3) Screening tests in dypnea (3) C. Pulmonary function test A. Spirometry Peak Expiratory Flow Rate (PEFR) Forced Vital Capacity (FVC) Forced expiratory volune in 1 second (FEV 1 ) * Changes of spirometry in pulmonary disease FEV1 FVC FEV1/FVC PEFR Obstructive lung disease Restrictive lung disease Labaratory test (4) Screening tests in dypnea (4) D. Arterial Blood Gas Analysis (ABGA) - measures amount of dissolved O 2 & CO 2 in arterial blood cf. Oximetry: measures fraction of O 2 carried in hemoglobin - provides best measure for delivery of oxygen from atmosphere to blood - minor change in ventilation affect PaCO 2 level more significantly than PaO 2 level - Normal value in adult: mmhg at room air PaO 2 = 5 x FiO 2 - In any patient with dyspnea, presence of hypoxemia is worrisome. - S 739 -

- 대한내과학회지 : 제 73 권부록 2 호 2007 - Labaratory test (5) Screening tests in dypnea (5) A-a DO 2 (Alveolar arterial oxygen tension difference) Formula 1 A-a DO 2 = PAO 2 -PaO 2 = PIO 2 - (PaCO2 x 1.

40 40 30 " Cross Over " in severe asthma PaO 2 without O 2 - In patients with dyspnea, calculation of A-a DO 2 may give additional diagnostic clue.

4 - 대한내과학회지 : 제 73 권부록 2 호 Labaratory test (5) Screening tests in dypnea (5) A-a DO 2 (Alveolar arterial oxygen tension difference) Formula 1 A-a DO 2 = PAO 2 -PaO 2 = PIO 2 - (PaCO2 x 1.2) - PaO 2 = (760 - PB) x FiO 2 -(PaCO 2 x 1.2) - PaO 2 Formula 2 Normal A-a DO 2 : 4 + age/4 ph PaCO " Cross Over " in severe asthma PaO 2 without O 2 - In patients with dyspnea, calculation of A-a DO 2 may give additional diagnostic clue. - If A-a DO 2 <20, little possibility for parenchymal lung disease Day 1 Day 2 Day 3 Day 4 Day 5 (modified from Weiss EB, Stein M: Bronchial asthma, 3rd ed, 1993) Five major causes of hypoxemia Causes A-a DO 2 Examples Comments Alveolar O 2 High altitude, CO poisoning tension Ventilation CNS disorders(iicp), drugs, PaCO 2 compensation for metabolic alkalosis, COPD or severe asthma Diffusion Interstital lung disease rare resting hypoxema V/Q mismatch Pneumonia, pneumothorax, improves CHF, ARDS, pulmonary embolism with O 2 asthma, COPD Shunt ASD, VSD, AV malformation does no improve with 100% O 2 Q2: 얼마나심한천식발작인가? 2006 Severity of Asthma Exacerbations (1) Severity of Asthma Exacerbations (2) - S 740 -

5 - 최동철 : - Management of Asthma Exacerbations Community settings Q3: 어디서치료하나? - 최대호기유속의감소가 20 % 미만인가벼운천식발작은지역의료기관에서치료가능 - 속효성기관지확장제를몇차례흡입후 1 시간이내에상태가호전되면굳이응급실로보낼필요없음 - 호전될때까지전신스테로이드의처방을고려 Q4: 어떤치료제를사용하나? - S 741 -

6 - 대한내과학회지 : 제 73 권부록 2 호 년내과학회임상강좌 GINA 2006 update Management of asthma exacerbations in acute care setting 2007년내과학회임상강좌 GINA 2006 update Management of asthma exacerbations in acute care setting 2005 update Initial Treatment Inhaled rapid-acting β2-agonist, usually by nebulization, one dose every 20 minutes for one hour revision Initial Treatment Inhaled rapid-acting β2-agonist continuously for one hour update Treatment for Moderate Episode Inhaled β2-agonist and inhaled anticholinergic every 60 minutes Consider glucocorticosteroids Continue treatment 1-3 hours, provided there is improvement 2006 revision Treatment for Moderate Episode Oxygen Inhaled β2-agonist and inhaled anticholinergic every 60 min Oral glucocorticosteroids Continue treatment for 1-3 hours, provided there is improvement 2005 update Criteria for Severe Episode 2007년내과학회임상강좌 GINA 2006 update Management of asthma exacerbations in acute care setting Hx: high-risk patient PEF < 60% predicted/personal best Physical exam: severe symptoms at rest, chest retraction No improvement after initial treatment Treatment: Oxygen Inhaled β2-agonist and inhaled anticholinergic Systemic glucocorticosteroid Consider intravenous magnesium Consider subcutaneous, intramuscular, or intravenous β 2-agonist Consider intravenous methylxanthines 2006 revision Criteria for Severe Episode History of risk factors for near fatal asthma PEF < 60% predicted/personal best Physical exam: severe symptoms at rest, chest retraction No improvement after initial treatment Treatment: Oxygen Inhaled β2-agonist and inhaled anticholinergic Systemic glucocorticosteroids Intravenous magnesium Drugs in Emergency Tx (1) Sympathomimetic agents - Mechanism: activation of adenyl cyclase on airway smooth muscle - Do not inhibit late asthmatic reactions - Beta-2 selective agents preferred - MDI with spacer or Nebulizer vs Oral or IV,SQ route - Advantage: Rapid onset of action Good patient acceptance Effective bronchodilation with little tachycardia Wide therapeutic range - Proper technique is required for maximal effect Open vs Closed mouth technique MDI with spacer vs Nebulizer Increase Bronchodilatory effect of β-agonist & anticholinergics Time(min) salbutamol ipratropium Responses to 25 asthmatics after inhalation of either 200µg of salbutamol or 40µg of ipratropium (Ruffin et al. J Allergy ClinImmunol 59:136,1977) β 2 -adrenergic agonist Dosages for inhaled β 2 -adrenergic agonist for acute asthma in adults Drug available form dosage comments salbutamol MDI:100 µg/puff 2-4 puffs or 0.5~1ml safe for Pt without (=ventolin) solution: 5mg/ml every 20min x 3, cardiovascular disease then every hour terbutaline DPI:500µg/puff no MDI in Korea UDV: 5mg/vial 0.5-1ml fenoterol MDI:400µg/puff? not FDA approved ( NIH Guidelines for the diagnosis and management of asthma, 1991) - S 742 -

7 - 최동철 : - Drugs in Emergency Tx (2) Anticholinergics β 2 - 교감신경자극제와같이투여하면더효과적인가?" 그렇다 - 급성천식발작시 β-agonist 나항콜린제제의단독투여보다병용투여가효과적이다 (Rebuck et al. Am J Med 82:59,1987) - 흡입 β-agonist 투여후에도반응이불완전한환자들에게항콜린제제를투여하였더니폐기능이호전되었다. (Bryant et al. Chest 102:742,1992) 아니다 - 오히려 paradoxical brochospasm 을유발하였다 (Conolly et al.,1982; Mann et al.,1984;rafferty et al.,1988) - 만성천식치료에서항콜린제제의효과는아직입증되지않았다. (Int'l consensus report on Diagnosis and Management of Asthma) Drugs in Emergency Tx (2) Methylxathines (1) - Mechanism: not clear phosphodiesterase inhibition Stimulation of catecholamine release Prostagladin antagonism Inhibit release of proteolytic enzymes or O2 metabolites - Narrow therapeutic range with severe side effects - Tight dose adjustment required - Linear relationship between Bronchodilatory effect and Log(serum level) - Ideal serum concentration: 10-12µg/ml - Additive effect with oral or inhaled beta2 agonist? Drugs in Emergency Tx Methylxanthines (2) Algorithm for IV aminophylline for acute asthma Increase in FEV1 Obtain Hx Hxof of theophylline Mx Mxin in previous 24hr check level or or 2.5mg/kg loading Loading 5mg/Kg Start continuous IV IV via via infusion pump child>9yrs & smoker: 0.6mg/kg/hr non non smoker without CHF or or CLD: 0.4mg/kg/hr CHF or or Liver dysfunction:0.2-0,3mg/kg/hr Check serum level 4-6hrs after IV IV infusion(tdm) 1 5 TheophyllineBlood level(µg/ml) >20microgram/ml Stop Stop infusion decrease rate rate by by 20% 20% Continue IV IV infusion <10 Additional Loadig 1mg/kg increase rate rate by by 20% 20% Drugs in Emergency Tx (3) Corticosteroid 전신스테로이드 (systemic corticosteroid) Drugs in Emergency Tx (4) IV magnesium sulphate - 가벼운천식발작에서는사용할필요없지만중등증이상의천식발작에사용하면천식증상의호전이빠르다. - 경구로투여해도효과가있으나최소한 4 시간은있어야효과가나타난다. - 만약경구투여가불가능하면주사로투여한다. - 경구투여시하루에 methylprednisolone 60-80mg 상당의스테로이드를 1 번투여 - 주사투여시 hydrocortisone mg 상당을수회에걸쳐투여한다. - 급성발작의치료를위해서대부분의성인환자는 1 주일, 소아환자는 3-5 일정도면충분하다. - 모든천식발작에권장되지는않음 - 내원당시 1 초간노력성호기량이예측치의 25-30% 정도이고치료 1 시간후에도예측치의 60% 미만인환자에투여하면효과적이라는보고가있음 -2g 을 20 분에걸쳐 1 회정맥투여한다. - S 743 -

8 - 대한내과학회지 : 제 73 권부록 2 호 Drugs in Emergency Tx (5) Other Treatment used in Asthma Tx (NIH Guidelines for asthma, 1991) Antibiotics: purulent sputum,fever,leukocytosis Hydration: In adult, aggressive hydration does not play a role in Tx of severe asthma Chest Physical Therapy: may be beneficial Mucolytics: Intra-bronchial Tx is contraindicated Sedation: Anxiolytics&Hypnotics should be strictly avoided in severe adult & child patients Status Asthmaticus (1) (Bronchial Asthma,E.Weiss et al,1993) Definition: No specific Criteria Severe,Life threatening airflow obstruction which is refractory to Initial bronchodilator therapy Incidence: No precise statistics Children>Adult, Female>Male Underlyng Pathology: Hyperinflated Lungs Airway Occlusion by Mucus Goblet cell Meta&Hyperplasia Bronchial muscle hyperplasia BM thickening Status asthmaticus (2) (Bronchial Asthma,E.Weiss et al,1993) Ventilator Therapy in Bronchial Asthma(1) (Bronchial Asthma,E.Weiss et al,1993) Risk Factors for Status Asthmaticus & Mortality Demographic: Young age, Non-Caucasian Historical: Prior life threatening attack,er visit>3 in last 1yr, Hx of Syncope,Use 3< drugs or steroid,lung Disease Psychosocial: Poor compliance,alcoholism,smoking,denial, Depression,Delay in seeking medical care Physician Related Factors Failure to diagnose severity of attack Underutilization of corticosteroid Failure to F/U & monitor using objective measures Inappropriate use of sedatives or narcotics Failure to Educate patients Indications for Ventilator in Asthma 1) Clinical Exhaustion,Apnea,Altered Consciousness Resp.muscle fatigue,cardiac or Hemodynamic instability 2) ABGA & Spirometry a. Rising PaCO 2 >40-50mmHg despite aggressive Tx Rise in CO 2 >5-10mmHg/hr with respiratory acidosis b. PaCO 2 >60mmHg with coexistng acidemia(ph<7.2) c. Refractory Hypoxia(PaO 2 <50nnHg with FiO 2 1.0) or O 2 induced ventilatory suppression d. FEV 1 <1.0L or <25% of predicted e. PEFR<120L/min or <25% of predicted Ventilator Therapy in Bronchial Asthma(2) (Bronchial Asthma,E.Weiss et al,1993) Ventilator Technic - Sedation: Benzodiazepines Narcotic if needed(fentanyl>morphine) - NM blocker if Pt fights or Severe tachycardia/tachypnea persist Goals of Mechanical Ventilation a. Limiting PAP<50-55cm H 2 O b. Keeping intrinsic PEEP<15cm H 2 O c. O 2 saturation>90%(fio 2 set to attain PaO mmHg) d. Normalize PCO 2 (TV 10-12ml/kg, RR 12-15/min, flow<60l/min) e. adjust I:E ratio - Controlled Hypoventilation: To prevent Barotrauma Hypercapnea is well tolerated if ph maintained> ) Pharmacologic Therapy(24) Ventilator Therapy in Bronchial Asthma(3) (Bronchial Asthma,E.Weiss et al,1993) Considerations for Weaning Mean duration for Ventilator Tx : hrs Criteria for Weaning from Ventilator a. A-a PO 2 difference< mmhg at FiO b. Adequate PaO2 at FiO 2 <0.4 c. VC > 10-15ml/Kg d. Normal range PaCO 2 with VE<10L/min e. Ability to generate inspiratory Pr>-30cmH2O and f. Clinical Findings support above data g. Obvious improvement in auscultatory findings h. Resolution of contributing factors - S 744 -

- 최동철 : - 증례 : 쌕쌕거리고숨이차서응급실로온 45 세여자 Case Present illness 07.9

20 증상호전없어서 D 의료원방문 CBC 15330-14.6-346K ABGA: ph 7.71, P CO2 12.4, P O2 129

9 - 최동철 : - 증례 : 쌕쌕거리고숨이차서응급실로온 45 세여자 Case Present illness 07.9 월초 fever, cough, dyspnea 발생 숨쉴때쌕쌕소리가나기시작 dyspnea 악화되어인근병원방문 RR>30, wheezing on both lung field R/O asthma attack, r/o Pn 로 iv steroid, iv moxi 증상호전없어서 D 의료원방문 CBC K ABGA: ph 7.71, P CO2 12.4, P O2 129 HCO3-16.3, SpO2 99% 증상호전없이본원 ER 로 refer P/E Laboratory finding V/S 115/ mental alert acute ill looking appearance not anemic conjunctiva, anicteric sclera chest: RHB s m, whole lung field wheezing Abd: soft and obese T/RT(-/-) normoactive bowel sound no organomegaly CVAT(-/-), edema(-) ABGA ph 7.67, pco2 17.4, po2 116, HCO3-19.7, SaO2 99% CBC K CRP 0.05 Chest routine CT Q1: 추가로필요한검사는? - S 745 -

10 - 대한내과학회지 : 제 73 권부록 2 호 Flow - volume curves in dyspneic patients Bronchoscopy: No endobronchial lesion R/O status asthmaticus flow expiration volume inspiration Normal Fixed intra or extrathoracic variable extrathoracic variable intrathoracic Final diagnosis Q2: 진단은? Vocal cord dysfunction R/O Panic disorder R/O Conversion disorder 입원기간 iv steroid에호전없이asthmatic attack 발생하여수초내정상화되는양상반복되었으나, risperidone, alprazolam, diazepam 등의 mood stabilizer 복용하면서 attack 없어져퇴원함. - S 746 -

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untitled 不年療理不類療 ˍˍˍˍˍ 不 1.25 2 1~80 不 1 (anatomic dead space) (cartilaginous airways) (noncartilaginous airways) (respiratory bronchioles) (alveoli) 2 列 (asthma) (pulmonary emphysema) 兩量 (diffusion capacity)