Deep discoveries: Treating respiratory infections in the ED. Brian H. Rowe, MD, MSc, CCFP(EM) Canada Research Chair in Emergency Airway Diseases Department of Emergency Medicine University of Alberta
Respiratory Conflicts Support for the studies reported in this talk: CIHR (ON); University of Alberta Hospital Foundation (AB); Canadian Assoc. of Emergency Physicians (CAEP); Department of Emergency Medicine, U of Alberta; The presenter is not a paid employee or consultant for any sponsor except the University of Alberta. Research funding and speakers fees for COPD- related topics from: GSK, AZ.
Outline Acute respiratory infections. Asthma, COPD, pneumonia (viral and bacterial) Evidence-based approaches: Antibiotics; Systemic corticosteroids; NIV. Emerging issues: Resistance, antibiotic duration and admission decisions. Summary.
Dyspnea how it should be treated!
Dyspnea sadly, this is how it is treated.
Case Presentation 31 year old male patient with history of asthma since age 8. Gradual deterioration X 3 days with exposure to dust; cough, SOB, and sputum x 3 days. Never smoked, no IN2B8 Ns; last admit ~ 12 years ago. O/E: short sentences; 1:2 = I: E; work of breathing; diffuse wheezing. Vitals: PR = 118/min (NSR) RR = 28/min T = 36.8 C SaO 2 = 94% Severity assessment? Differential Dx? Treatment?
Laboratory tests CBC: WBC = 19.4 (17 PMNs); Hgb = 145 Lytes - normal Urine normal. Spirometry: FEV 1 /FVC = 55% predicted; FEV 1 = 45% predicted improved with SABA.
Radiograph (not always needed)!
Pathophysiology - Asthma Definition: multi-factorial chronic respiratory disease, characterized by a history of intermittent symptoms (cough and/or wheeze and/or breathlessness) exacerbated by irritants (URTI). Pathophysiology of the acute episode: Primary: Airway inflammation; Secondary: Airway bronchospasm; Long-term:? Fixed airway obstruction. Acute treatment addresses primary inflammation and bronchodilators for reversible airway obstruction.
Asthma First line agents: Salbutamol + IB (MDI vs nebs) repeatedly; Systemic corticosteroids. Second line: MgSO 4 IV 2 grams over 20 minutes; ICS (variable doses). Final efforts: IM epinephrine (? allergy); NIV.
Asthma and infections Most infections i in acute asthma are viral. Antibiotics are not recommended as first line agents (but often used). Antibiotics are indicated d with signs of infection: fever, +ve sputum, new infiltrate on CXR. If failed aggressive anti-inflammatories, inflammatories, some pulmonary specialists suggest a trial of broad spectrum antibiotics after a week.
Case Presentation 80 year old male patient with emphysema. Gradual deterioration X 10 days cough, g, SOB, and sputum x 3 days. Ex-smoker X 1 year (60 pack years); Combivent (QID) + Theodur; Allergy: levo-something. O/E: tripod posture ;1:3=I:E; work of breathing; A/E to bases. Vitals: PR = 120/min (AF) RR = 40/min T = 37.9 C SaO 2 = 80% Severity assessment? Differential Dx? Treatment?
Radiograph
Pathophysiology - COPD Definition: chronic disease, mainly caused by tobacco exposure, characterized by a history of progressive symptoms (cough and/or wheeze and/or breathlessness). Pathophysiology of the acute episode: Primary: Airway infection; Secondary: Airway inflammation; Long-term: progressive decline in lung capacity. Acute treatment addresses primary infection and inflammation with underlying non-reversible airways.
ED COPD COPD exacerbations are common emergency department presentations. Exacerbations result in significant: Costs to the health care system; Impairments in quality of life for patients. Serious sequelae very common: Admissions to hospital; Airway support: NIV, IN2B8 ns; Death (fastest rising cause of CD death).
Classification of exacerbations Type 1 Increased dyspnea Increased sputum volume Increased sputum purulence Type 2 Two of the above Type 3 One of the above Anthonisen NR et al. Ann Intern Med 1987;106:196-204.
Bronchodilator choices Not as clear cut as asthma. Both salbutamol and IB are effective. Synergy: Not as effective. Side effects: More pronounced with salbutamol. Delivery: er MDI + spacer vs nebs in 2011.
Corticosteroids in Exacerbations of COPD
All evidence Systemic corticosteroids id vs placebo: Cochrane Review: high quality; Involving 11 trials and >1080 adult patients; Outcomes: Fewer treatment failures within 30 days (OR = 0.50; 95% CI: 0.36 to 0.69) NNT = 10. LOS (Hosp): -1.2 days (95% CI: -2.3 to -0.2); Caveat: S/Es(OR=23;95%CI:16to34) 2.3; 1.6 3.4). Walters H, et al. Cochrane Database Syst Rev. 2009; 1:CD001288.
Corticosteroids after discharge Emergency Department discharge Emergency Department Treatment R Prednisone 40 mg po OD X 10 days Combivent 2 puffs QID + antibiotics Placebo prednisone Combivent 2 puffs QID + antibiotics Visit: 1 PC1 2 Week: 0 10-14 days 4 weeks Aaron S, et al NEJM 2003; 348:2618-24.
Prednisone for Out-Patient Acute Exacerbation of COPD Aaron S, NEJM 2003:348
Summary NNT: 7! Other outcomes: congruent. Systemic corticosteroids are effective in the early treatment t tof acute severe COPDto prevent admission and the out-patient treatment of COPD to prevent relapse. S/E s are impressive, so selection must be appropriate.
Antibiotics in Exacerbations of COPD Who needs them and which ones do you use?
Effectiveness of Antibiotics in COPD Placebo Antibiotic % Success s 80 70 60 50 40 30 20 10 0 Type 1 Type 2 Type 3 Anthonisen NR et al. Ann Intern Med 1987;106:196-204. Anthonisen NR et al. Ann Intern Med 1987;106:196-204.
All evidence Systemic antibiotics i vs placebo (Type II/I): SR: high quality; Involving 11 trials and >900 adult patients; Outcomes: Lower mortality (RR = 0.23; 95% CI: 0.1 to 0.5) NNT = 10. Fewer treatment failures (RR = 0.47; 95% CI: 0.4 to 0.6) NNT = 3. NB: not influenced by the antibiotic choice. Ram F, et al Cochrane Database Syst Rev. 2006; 2:CD004403
Canadian Guidelines O'Donnell D, et al. CRJ 2007; 14:5B-32B
Antibiotic Considerations Duration of treatment? 5 = 10 days
Summary Systematic ti review (21 studies; 10,698 pts). A short course of antibiotics (5 days) seems to be just as effective in achieving clinical and bacteriological cure rates as a longer course (7-10 days). Given the side effects of antibiotics and the elderly nature of COPD patients, it seems reasonable to reduce the duration of antibiotics in this patient population. Moussaoui RE, et al. Thorax 2008; 63: 415-422
Short (< 5 days) vs long (>7 days) Moussaoui RE, et al. Thorax 2008; 63: 415-422
Question NIV in Exacerbations of COPD
NIV
The evidence Design: 10 RCTs (> 750 patients). Population: Acute severe COPD. Interventions: NIV. Control: standard care. Outcomes: Death, intubation, LOS High quality methods for SRs Ram FSF, et al. CDSR. 2004, Issue 3.
NIV treatment failures Ram FSF, et al. CDSR. 2004, Issue 3.
NIV Mortality outcome Ram FSF, et al. CDSR. 2004, Issue 3.
NIV Intubation outcome Ram FSF, et al. CDSR. 2004, Issue 3.
Summary NIV reduces treatment failures, mortality and intubations in the ED. Complications associated with treatment (RR 0.38; 95% CI 0.24 to 0.60) and length of hospital stay (WMD -3.24 days; 95% CI -4.42 442to -2.06) were lower with NIV.
Case #3 72 year old female with week history of dyspnea, Lives with demented husband. Ex-smoker 8 pack years. HTN, hyperlipidemia. Vitals: PR = 104/min (NSR) RR = 32/min T = 37.9 C SaO 2 = 83% Severity assessment? Differential Dx? Treatment?
Radiograph
Viral pneumonia The Id don t get no respect of pneumonia. Common cause of CAP (variable up to 32%). Predominant causal agents: Influenza, RSV, rhinovirus, H1N1... 2010 study identified #1 agent: coronavirus. Bacterial CAP on antibiotics often coinfected with viruses. Lieberman D, et al. Chest 2010; 138: 811-816.
Investigations CXR: Recommended in all ED patients with suspected pneumonia. CBC/lytes/other labs: complex / severe cases: Microbiology: Blood: admitted patients with fever only; Sputum cultures: non-response?; PCR swabs for suspected viral CAP. Personalized tests (limited application): CRP, Procalcitonin, urinary antigens.
Radiography +ve CXR treat (look for abscess and pleural effusion [PSI]). False negative CXR can occur if severe dehydration or too early in course illness. A patient with negative CXR, signs and symptoms should be treated and followed closely. ED physicians (+vs /-ve CXR) treated the same, outcomes similar.
Assessment of Severity Prognosis is difficult to predict in moderatesevere CAP; some clinical prediction rule is better than gestalt. Pneumonia Severity Index (PSI): PSI is based on 20 variables that are used to derive a score; Enables patients to be stratified into five risk categories based on 30-day mortality. Alternatives: CURB - CTAS? - CRB65
BTS Approach
Which should you use? SR of 40 studies and 81,797 30-day mortality patients (8.3% mortality) compared PSI, CURB-65 and CRB-65. Performance characteristics were similar across comparable cut-offs for low, intermediate and high risk for each score. CRB-65 had fewer low risk category pts. Chalmers JD, et al. Thorax. 2010;65:878-883
Antibiotic Considerations I Empiric therapy?
Empiric antibiotic decisions IDSA (2007) - outpatients: First line: macrolide, doxycycline; Second line: respiratory fluoroquinolone. IDSA (2007) - inpatient: First line: respiratory fluoroquinolone; Second line: β-lactam plus macrolide. IDSA (2007) - ICU: First line: β-lactam plus azithromycin. Note: many recommendations are consensusbased.
Emerging Issues Corticosteroids, Antibiotic Resistance, and Performance Indicators.
Corticosteroids in pneumonia CDSR: 6 studies including 437 participants: i unable to make recommendations. Recent Lancet PICO-D: P: 304 pts with CAP admitted through ED; I: Dex 5 mg IV X 4 days + antibiotics; C: placebo + antibiotics; O: LOS; D: RCT. Results: 6.5 (dex) vs 7.8 (control) days. Chen Y, Li K, Pu H, et al.cdsr Mar 2011
Representative Canadian Data Vanderkooi OG, et al. Can J ID Med Microbiol 2009;20(4):e139-e144.
Effect of Prior Antibiotic on S pneumoniae Resistance susceptib ble) Percent resistant t (or non- 40 35 30 25 20 15 10 5 0 No (or no known) antibiotic use Any prior antibiotic Prior use same class P enicillin Cefotaxime Erythromycin Tmp/Smx Quinolones Vanderkooi OG, CID 2005;40: 1288-97
Performance indicators Increasing focus on how we do things. Proposed indicators can be gamed (Abx < 4 hours) and may not be evidence-based. ICES survey identified d KPIs for quality care in the ED. Respiratory (8): Asthma (4): % received CS in ED and at D/C; COPD (1): % received CS in ED and at D/C; CAP (3): time to antibiotic therapy. Schull M, et al. ICES. 2010 (CJEM in press)
Antibiotic duration New paradigm: go hard and go home. Shorter courses of antibiotics may eradicate infection and decrease SAEs. Examples: AOM, UTI, etc. Overall evidence not as clear as COPD; however, out-patients don t need to be treated for as long as 10-14 days.
Summary: Respiratory infections More expansive antibiotic i choices, although h the pipeline is drying up. Selective use of antibiotics (old is new); Empiric choices based on guidelines. Atypical and viral pathogens are increasingly common: Viral pneumonia (H1N1, influenza, etc); Management guidelines and local practice. Bacterial resistance stable 3 month queries.
Thanks for listening! Questions for Sam?