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Emergency Management of Pneumonia Dr. Andrew Morris 2009.07.13

Objectives Mine to be as brief as possible to be practical to be informative to be provocative

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Objectives Yours

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to appreciate the epidemiology of communityacquired pneumonia to understand how CAP can be missed ... or diagnosed in lieu of another (correct) diagnosis to be able to sanely prescribe antibiotics: safely, but rationally also to get out of lunch rounds early without having to be “paged” out

Pathogenesis

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for almost all pneumonia (save influenza, TB and a few others), the pathogenesis is the same

Pathogenesis

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for almost all pneumonia (save influenza, TB and a few others), the pathogenesis is the same

Pathogenesis

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for almost all pneumonia (save influenza, TB and a few others), the pathogenesis is the same

Pathogenesis

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for almost all pneumonia (save influenza, TB and a few others), the pathogenesis is the same

CAP epidemiology

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approximately 4.5 million cases annually 80% of cases are managed as outpatients 62 000 deaths/year (adjusted mortality rate of 22/100 000) in US 1.4 million hospital discharges in US in Canada, the mortality rate for CAP hovers around 12/100 000 American Lung Association, July 2007 www.cdc.gov www40.statcan.ca

CAP epidemiology

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Change in coding from ICD-9 to ICD-10 in 1999

Pneumonia age-adjusted death rates based on the 1940 and 2000 standard populations, 1979-2003 American Lung Association, July 2007

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Outpatient pneumonia is a benign disease

“Among the 1575 patients in the three lowest risk classes in the Pneumonia PORT cohort, there were only seven deaths, of which only four were pneumonia-related.” only 1 of these 7 patients were managed as an outpatient.

NEJM 1997;336:243-50

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In-hospital case-fatality is low in young people administrative database from Alberta, looking at all CAP admission from 1994-1999 in adults 18-55 in-hospital case-fatality: 3.2%

15%

10%

5%

0%

10-day case-fatality: 2.1% (most deaths attributed to macroaspiration)

11.9%

4.5% 1.6%

Case-fatality rate

18-39

40-54

≥55

Clinical Infectious Diseases 2003;36:413–421

Summary

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pneumonia is usually caused by microaspiration and then replication of pharyngeal bacteria most pneumonia is a benign disease, especially in young persons

CAP epidemiology

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most commonly isolated organism, by destination: outpatient: S. pneumoniæ inpatient: S. pneumoniæ ICU: S. pneumoniæ cemetery/crematorium: S. pneumoniæ however: in patients going to ICU, S. aureus (incl. CA-MRSA) and Legionella (and Gramnegative bacilli) are frequently isolated Mycoplasma, Chlamydophila, H. influenzæ, and viruses are frequently found in outpatients/ ward patients

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Pt. in ER referred for “Pneumonia” most likely Dx: Pneumonia (50-60% of the time) other possibilities: acute bronchitis CHF COPD/asthma exacerbation pyelonephritis pulmonary embolism others Arch Intern Med 2008;168:351-356

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Pt. in ER referred for “Pneumonia” initial assessment: does this patient need to be isolated before I see him/her? ABCs do a relevant history and physical examination

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Relevant history for “Pneumonia” is it pneumonia? fever (LR+ 2.1, LR- 0.7) cough (LR+ 1.8, LR- 0.31) chills (LR+ 1.7, LR- 0.85) sweats (LR+ 1.7, LR- 0.83) asthma (LR+ 0.1, LR- 3.8) rhinorrhea (LR+ 0.78, LR- 2.4) there is no combination of features on history that is suitably reliable for the diagnosis of pneumonia

Ann Emerg Med 2005;46:465-467

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Relevant history for “Pneumonia” what kind of pneumonia? risk of TB? sick contacts?* travel? animal exposure?* specific forms of immunosuppression prolonged neutropænia: Aspergillus TNF inhibitors: Mycobacteria steroids, “transplant” meds: PCP, other (esp. dimorphic) fungi

Relevant physical exam for “Pneumonia”

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does patient have pneumonia? Any vital sign abnormality (LR+ 1.2–4.4, LR- 0.5–0.8) Any chest finding (LR+ 1.3, LR- 0.57) Crackles (LR+ 1.6–2.7, LR- 0.9) Egophony (LR+ 8.6, LR- 0.96) Dullness to percussion (LR+ 4.3, LR- 0.93) Decreased breath sounds (LR+ 2.6, LR- 0.64) Asymmetric respirations (LR+ Infinity, LR- 0.95) Ann Emerg Med. 2005;46:465-467

Relevant physical exam for “Pneumonia”

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does patient need resuscitation? is this severe? home vs ward vs ICU? PORT score is best validated for overall severity, and so should stick with it CURB-65 widely touted and easy, but not as well validated SMART-COP appears best for deciding about ICU care

PORT Score

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http://pda.ahrq.gov/ clinic/psi/psicalc.asp

NEJM 1997;336:243-50

PORT Score

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NEJM 1997;336:243-50

CURB-65

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2004 BTS Guidelines Update: http://www.brit-thoracic.org.uk/ ClinicalInformation/Pneumonia/PneumoniaGuidelines/tabid/136/Default.aspx

SMART-COP

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IRVS: Intensive respiratory or vasopressor support

Clinical Infectious Diseases 2008; 47:375–84

Investigations minimum: CBC; INR/aPTT lytes, urea, creatinine, glucose liver enzymes SaO2 and/or ABG blood C&S x 2 urine R&M +/- C&S CXR

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consider: D-dimer and other tests re: PE ECG troponin sputum Gram stain/ culture sputum for AFB Legionella urinary antigen np swabs for resp. viruses

Chest X-ray

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although widely recommended (and intuitive), evidence supporting the utility of X-ray is lacking (problem = no gold standard) CXR is not helpful to predict ætiology at 2 weeks, only 51% of patients had CXR resolution (and only 73% at 6 weeks) clearance of CXR is slower in the elderly repeat CXR, though often recommended at 6 weeks, is probably only of value in those who have not fully resolved Am J Respir Crit Care Med 1994;149:630–5

Investigations

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evidence-based medicine does not support the notion that organisms can be predicted on the basis of history, physical examination and chest x-ray the term “atypical” pneumonia should not be used

Summary

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patients referred from the ER with pneumonia often have other primary diagnoses cough, constitutional symptoms, and abnormal chest findings are helpful to “rule in” pneumonia, but cannot rule it out investigations should focus on alternative diagnoses and identifying severity

Treatment

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controversial guidelines say one thing, evidence says another guidelines vary from country to country I will give you my take, but feel free to: a) ignore b)argue c) disparage d) follow

Atypical pathogens

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Testing testing is problematic: Legionella urinary antigen is specific, but not tremendously sensitive (< 80%) Mycoplasma IgM is specific, but is usually available post-treatment Chlamydia testing is unreliable

Atypical pathogens

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Treatment

there are 3 meta-analyses that have looked at treatment of CAP 1 meta-analysis involving 18 trials and 6749 participants: no difference when covering for atypicals 1 meta-analysis focused on outpatients involving 13 trials and 4314 patients: no difference when covering for atypicals 1 meta-analysis focused on inpatients involving 24 trials and 5015 patients: no difference when covering for atypicals BMJ, doi:10.1136/bmj.38334.591586.82 Eur Respir J 2008;31:1068-76 Arch Intern Med 2005;165:1992-2000

CAP

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Treatment Quiz which of the following agents have been associated with bacteriologic failure (i.e. clinical failure due to failure to treat the S. pneumoniæ) in pneumococcal pneumonia? a) azithromycin b) ceftriaxone c) cefuroxime d) levofloxacin e) penicillin answer: a), c), d)

CAP

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Treatment there is not a single randomized, blinded trial that has ever shown one agent or a combination of agents to be superior to penicillin for CAP because S. pneumoniæ is the most likely pathogen, covering it receives the highest priority options for treating S. pneumoniæ penicillin or ampicillin (i.v.)/amoxicillin (p.o.) cefotaxime or ceftriaxone doxycycline respiratory FQ (levofloxacin or moxifloxacin)

CAP

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Treatment - ICU for patients heading to the ICU, the approach should differ, because you need to cover for S. aureus (sometimes including MRSA) and Legionella in addition to S. pneumoniæ options (and there are many more, none based on RCTs): ceftriaxone + (respiratory FQ or macrolide) +/vancomycin +/- oseltamivir OR vancomycin + (respiratory FQ or macrolide) +/oseltamivir ceftriaxone + TMP/SMX (for CA-MRSA and Legionella) +/- oseltamivir

CAP

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Treatment-Antivirals

there are no RCTs demonstrating a mortality benefit of antiviral therapy for CAP studies of influenza in otherwise healthy adults with influenza showed that neuraminidase inhibitors shorten duration of illness by about 1 day

N Engl J Med 2005;353:1363-73

CAP

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Treatment-Antivirals meta-analysis of trials prior to 2002 involving influenza+ high-risk patients >65 yrs or with chronic medical conditions reported zanamivir ➡time to alleviation of symptoms by 2d and that oseltamivir did so by about ½ day a Canadian study in long-term care facilities showed that elderly patients given oseltamivir within 48 hours after onset of symptoms were considerably less likely to be prescribed antibiotics, to be hospitalized, or to die BMJ 2003;326:1235

CAP

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Treatment-Antivirals prospective study from January 2005-May 2006 of patients hospitalized with influenza in southern Ontario 327 adults (median age 77; 75% with chronic underlying illness) 89% received antibacterials; 32% prescribed antivirals 36% of those no receiving antivirals were admitted to ICU, compared with 16% 22% vs 4% 15-day mortality Clin Infect Dis 2007;45:1568-75

Summary

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treatment of patients for CAP should include an agent expected to be effective for S. pneumoniæ if patients are heading to the ICU, then cover for Legionella and CA-MRSA if there is plenty of influenza going around, add oseltamivir

CAP

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After Day 1 there is little evidence to support followup investigations in patients who are clinically improving leukocytosis and CXR do not correlate well with clinical improvement: treat the patient, not the labs give at least 72h to respond if hæmodynamically stable, eating and improving, can probably step-down to oral therapy as a minimum, a chest x-ray should be performed at 6 weeks (to ensure resolution) if patient not clinically back to baseline health

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CAP

After Day 1: Misbehavin’ patient not responding resistance/ inadequate therapy empyema/effusion alternate diagnosis

patient worsening natural history of disease resistance/ inadequate therapy secondary infection alternate diagnosis

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CAP

After Day 1: Misbehavin’ Effect of Therapy on Percent Survival in Pneumococcal Bacteremia 100 90 80

% Survivors

70 60

Symptomatic

50

Serum

40

Penicillin

30 20 10 0 0

5

10

Day of Illness

15

20

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QUESTIONS?