COPD is one of the more common respiratory issues we encounter in the ED. It affects approximately 5% of the US population and is the 3rd leading cause of death and 12th leading cause of morbidity in the US.

The predominant risk factor for COPD is cigarette use with ~80% of patients with COPD in the US having a history of cigarette use. Interestingly, of all cigarette smokers, only ~15% will develop COPD during their lifetime. Of the 20% not caused by tobacco use, the vast majority result from genetic (e.g. alpha-1 antitrypsin deficiency), environmental, or occupational risk factors for COPD (e.g. certain chemicals or vapors).

COPD Background

COPD is a complex progressive disorder that typically occurs over years and decades. In fact, the vast majority of patients with COPD have >15-20 years of tobacco use and are often >45 yoa before symptoms become evident. Classically, COPD is divided into 2 subsets:   chronic bronchitis (blue bloater) and emphysema (pink puffer). However, most patients display symptoms of both. Chronic bronchitis is defined as near daily cough with sputum production for at least 3 months per year for 2 consecutive years caused by chronic inflammation, which leads to narrowing of the bronchial airways. Emphysema is characterized by the destruction of the elastic fibers of the alveoli, which leads to impaired outflow of air and lung trapping.

Blue Bloater:Pink Puffer

COPD Exacerbation Background

COPD is often diagnosed in the outpatient setting and still relies primarily on history and physical exam. Spirometry also plays helpful role in diagnosis with COPD being defined as FEV1:FVC ratio <0.70.

In the ED, we are more likely to encounter a COPD exacerbation rather than a new diagnosis of COPD. The Global Initiative for Chronic Obstructive Lung Disease (GOLD)–part of WHO–defines COPD exacerbation as “an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication.” Often, this is clinically apparent by an increase in cough frequency or severity, changes in sputum volume and/or color, or worsening of wheeze or dyspnea.

Respiratory infections are estimated to trigger ~70% of COPD exacerbations. The remaining 30% are often due to environmental triggers (e.g. pollen, pollution, etc.), idiopathic, or pulmonary embolus. In fact, a study in Chest from 2009 that included systemic review of literature that included 550 patients admitted for COPD found nearly 20% of patients admitted for COPD exacerbation had a PE (Prevalence of PE in Acute Exacerbations of COPD: A Systematic Review and Metaanalysis (2009)). The increased risk for PE is likely multifactorial as these patients often endure limited mobility, chronic inflammation, and often suffer from other comorbidities like diabetes, PVD, and CAD. This does not mean that all patients arriving with COPD exacerbation need a D-dimer or CT scan, but that it should be in the back of our minds and on our differential for a patient that is not responding well to our typical management. Again, this study looked at solely admitted patients (who would be more likely to not respond to our typical management). Therefore, patients who improve in ED and to be discharged would have lower suspicion for PE.

COPD Exacerbation Work-Up

  • History is a great way to risk stratify patients. Similar to asthma, patients with hx of recurrent hospitalization, use of home oxygen, hx of Bipap use, hx of intubation, recent antibiotic use, or recent steroid use, have a higher propensity for more severe COPD exacerbation
  • Physical Exam
    • Early disease:  more common to see mild tachypnea and end expiratory wheezing. May have signs of hyperinflation of lungs (e.g. increased resonance on percussion, distant heart sounds, CXR with flattened diaphragm or narrowed heart).
    • As disease progresses, may have more severe wheezing that includes inspiratory wheeze and more severe tachypnea. May also find signs of right heart failure (“cor pulmonale” with enlarged liver and peripheral edema)
    • Respiratory distress can include signs of accessory muscle use including tripodding, conversational dyspnea, Paradoxical chest/wall abdominal movements (“Hoover’s Sign”–see below), cyanosis, and asterixis (from severe hypercapnia).
      • COPD paradoxical breathing
    • Physical exam should also help to look for other potential diagnoses (fever, hypotension, peripheral edema, etc.)
  • Labs/Imaging
    • CBC:  may see polycythemia from chronic hypoxemia (seen more on boards than in ED)
    • BMP:  compensatory metabolic alkalosis (increased bicarbonate to offset chronic increase in pCO2)
    • VBG/Lactate:  lung trapping can lead to elevated pCO2 and respiratory acidosis. Of note, high pCO2 may be patient’s baseline so useful to compare to past VBG if available. This lab can also be helpful for trending in ED. For instance, if start patient on Bipap, then can repeat VBG/lactate to compare to initial VBG. If improving, keep rocking the BiPap, but if VBG worsening, then likely need to be considering intubation vs. Bipap setting adjustments.
    • EKG:  Check for ischemic changes. Often these patients are presenting with dyspnea at increased age
      • May also check troponin
    • BNP:  concomitant heart failure
    • Influenza Test:  if in season, clinical signs, or sick contacts. These patients have indication for oseltamivir treatment
    • CXR:  r/o pneumonia and/or pneumothorax (more prone to PTX as often have bullae/blebs from COPD)
    • Procalcitonin:  not available at Rush but may see at other sites as has good evidence of ruling out bacterial cause of pulmonary infection
    • Sputum Cultures:  rarely needed and typically do not influence course
    • EtCO2:  There is poor evidence that EtCO2 correlates well with arterial pCO2. This is the only study I could find on the subject in COPD, and recommended against its use due to this poor correlation (European Journal of Emergency Medicine Value of EtCO2 in COPD in ED 2011). 
    • Peak Expiratory Flow:  Most literature advises against checking in COPD exacerbations as does not correlate well with severity of COPD exacerbation (this is in comparison to asthma exacerbation where is useful)

Treatment of COPD Exacerbations

Treatment of COPD exacerbations in the ED rely heavily on inhaled bronchodilators and steroid treatment. We’ll also discuss a few other adjunctive therapies as well as other supportive measures

Oxygen Therapy

ABC’s are 1st line for any illness in the ED. IV and O2 monitor all day. Goal of oxygen therapy is for O2 sat of 88-92%, not greater than 94%. Remember that the majority of these patients live at chronically low levels of O2, therefore, giving more oxygen than this can actually worsen their disease process by decreasing ventilatory drive and worsening their hypercapnia (RebelEM article of pathophysiology for this effect).

IV Fluids

Goal is for euvolemia. However, note that these patients are prone to hypovolemia in setting of high insensible losses (primarily from tachypnea, possible influence of fever). Caution in patients with crackles at bases and concomitant hx of CHF.

Beta-2 Agonists

Mainstay of COPD exacerbation treatment relies on beta-2 agonists primarily albuterol due its rapid onset and efficacy in producing bronchodilation. Albuterol is often given as 2.5 or 5 mg dose in ED.

Levalbuterol is another beta-2 agonist that may see. Initial advertisements stated that it was more specific to beta -2 receptors as was pure enantiomer, therefore, produced less tachycardia (beta-1 receptor) and produce greater bronchodilation. It was theorized this may be better for patient’s with hx of CAD or side effects of tremor or anxiety. However, most studies have shown little difference between the two, while levalbuterol remains more expensive (Am J Health Syst Pharm – Levabuterol vs. Albuterol (2015)). Would also likely be more challenging to get from pharmacy in urgent fashion the way we do with albuterol.

In very severe COPD exacerbations (e.g. leaning towards NIV or intubation), continuous albuterol is recommended. In more mild-to-moderate exacerbations, nebulized aerosols q20-30minutes is recommended (Annals of EM – Effect of different albuterol in COPD (1997)). This study included 86 patients in the ED that were randomized to albuterol 2.5 mg q1h vs. q20 minutes, and showed greater interval improvement in FEV1 at both 1-hr and 2-hrs in the q20 minutes group. There have been more studies on this in asthma, which is also where this recommendation derives from. Of note, higher frequency and dose were associated with more side effects of tremor, tachycardia, and mild hypokalemia.


Ipratropium is a short-acting anticholinergic that is most commonly used in ED. It is given as 0.5 mg or 2.5 mL of the 0.02% inhalant solution. Fun fact, we used to use aerosolized atropine (prior to 1990s), however, there is some systemic absorption with aerosolized atropine, which led to anticholinergic side effects like dry mouth, blurred vision, and urinary retention (primarily in elderly). Ipratropium is a structural analogues to atropine, but is not heavily absorbed in the lung, which is why it is now preferred.

Combined Beta-2 Agonist and Anticholinergics

This is what we most commonly see in the ED. We could write an entire blog on studies looking at the efficacy of single agent vs. combined use of these agents. The evidence is mixed, however, there has been evidence that shows occasional benefit in certain subsets of patients and overall an association with improved FEV1. Due to this, most favor employing the dual use of agents early in the hospital admission (e.g the ED).


There are several details to systemic steroids that we will discuss here including:  efficacy, dose, and IV vs. PO.

Efficacy:  Systemic steroids have shown lower rate of relapse in 30 days (defined as return to ED or unscheduled visit to PCP) with 27% for steroids and 43% without steroids. Patients also had sooner improvement of FEV1 and subjective improvement of dyspnea. Of note, patients in this study (included 147 patients from ED) also received 10 days of antibiotics and continued use of inhaled bronchodilators (NEJM – Outpatient oral prednisone after ED treatment of COPD). Recall that steroids work on the DNA level, therefore, you will not see their effect for at least 6 hours. 

Which Steroid:   There has not been a significant difference found among steroids. In the US, more commonly use prednisone and solumedrol, while in Europe, hydrocortisone is occasionally employed. One caveat to this is the use of decadron, which may be preferred in patients with poor access to medicine or follow-up as single dose in ED can provide few days of steroid coverage as half-life is 36-54 hours. Again there is no difference between PO or IM route.

IV Steroid vs. PO Steroids:  PO steroids have 100% bioavailability, therefore, there is no added benefit of giving medication IV. If patient is able to tolerate PO, then this is the preferred method due to cost.

Duration of Steroid Treatment:   Prednisone 40-60 mg/day for 5 days was non-inferior to same dose of steroids for 14 days (REDUCE Randomized Clinical Trial (2013)).

Dose of Steroid:  I could not find any direct randomized controlled trials regarding dose of steroids. There are retrospective studies regarding dose of steroids including patients who have received solumedrol 125 mg q6 vs. patients who have received prednisone 40 mg/daily. This is a vast heterogeneity in practice. However, most guidelines (GOLD, ATS/ERS, Canadian Thoracic Society) recommended low-dose steroids as limited side effects (hyperglycemia) and appeared to be associated with decreased hospital stay. This is the best study (High Dose vs. Low Dose Systemic Steroids (2016)) that I could find on the topic. Due to these guideline, the recommended dose for solumedrol would be 40 mg IV (not the 125 mg common in most order sets). For steroid conversion, MDCalc has a great one.

steroid conversion


Most guidelines suggest giving course of antibiotics in patients with change in sputum (either color or volume) or dyspnea/exacerbation requiring NIV or admission to ICU. Note that antibiotics are indicated in not just circumstances of pneumonia. The pathophysiology for the role of antibiotics is that these patients have change in their lung architecture and can become colonized by bacteria without necessarily having an infiltrate on CXR.

Antibiotics for COPD

Which Antibiotic to Use:  Goal of antibiotic coverage is to cover more common pathogens (e.g. H. influenzae, M. catarrhalis, S. pneumoniae, C. pneumoniae, and gram positive organisms like Staph and Strep.

Simple Coverage

  • Azithromycin 500 mg on Day 1 with 250 mg Day 2-5:  this was everyone’s favorite for a long time, and still plays role in more mild exacerbations where antibiotics may be indicated. However, recent study (Macrolide resistance in Cases of CAP in ED (2018)) showed nearly 20-25% of macrolide-resistant Streptococcus pneumoniae . However, of note, this study was looking at patients being treated for CAP while in ED and was not specifically looking at antibiotic use in COPD exacerbation without pneumonia.
  • Doxycycline 100 mg bid for 5-7 days
  • 3rd generation cephalosporin:  Cefdinir (Omnicef) 300 mg bid for 5-7 days or Cefpodoxime 200 mg bid for 5-7 days
  • Bactrim

Complex Coverage

  • These include patients with risk factors including:  >3 exacerbations/year, significant comorbidities (DM, HF, CAD, etc.), and antibiotics in last 3 months. Concern is for more resistant organisms including beta-lactamase producing S. pneumoniae, enterobacteriaceae, and pseudomonas)
  • Antibiotics include:  Cefepime, zosyn, levaquin for inpatient.
  • IDSA also included amoxicillin 1000 mg tid for 5-7 days or augemtin 875/125 bid for 5-7 days if patient is viable candidate for outpatient treatment but met above criteria

Oseltamivir (Tamiflu)

Just a reminder with flu season just starting to treat these patients. Dose is 75 mg bid for 5 days (remember to renally dose in CKD/ESRD)

IV Magnesium

Given as 2 gram IV dose over 20 minutes. The data is not as robust for IV magnesium in COPD as it is for asthma exacerbation. Annals of Thoracic Medicine – Magnesium Systemic Review (2014). However, there is a low side effect profile for IV magnesium (primarily hypotension, flushing, etc.), and it has a known bronchodilatory effect as seen in asthma exacerbations. Therefore, it may be considered early in patients arrival to ED where patient is in severe respiratory distress with goal of avoiding intubation.

Non-Invasive Ventilation (e.g. BiPap)

Bipap (note CPAP not as useful) has shown decreased intubation rates, improved short-term mortality, symptomatic improvement, and decreased length of hospital stays primarily in studies performed in 1990s including this NEJM – NIV in Acute Exacerbation of COPD (1995). Most often start at 10/5 (meaning inspiratory pressure 10 and expiratory pressure 5) with FiO2 set for pulse ox goal 88-92%. If pCO2 is not responding, then often increase inspiratory pressure in 2-point increments (e.g. 12/5 or 14/5). In some cases (e.g. significant breath stacking), it can be reasonable to place on reduced expiratory pressure of 3 (e.g. 10/3) as patient will have “auto-PEEP” in addition to this provided inspiratory pressure as well.

Goal of Bipap is to stent open smaller airways and to aid in work of breathing to improve ventilation and decrease pCO2. Can recheck blood gas 30 minutes after start of Bipap or changes in Bipap settings as 30 minutes allows for blood gas changes. Recall that if acute on chronic COPD exacerbation that they often live with some level of hypercapnia so a normal pCO2 35-45 is not physiologic for them. Also note the contraindications for Bipap (e.g. AMS, unable to clear airway secretions, hemodynamically unstable, or anatomical variance inhibiting use of Bipap mask)


This could also be its own blog topic so will only discuss briefly.

The goal of the above treatments is to avoid intubation as these patents have higher mortality (mostly from severity of their disease). Intubation is indicated in patients with worsening respiratory acidosis despite NIV, deteriorating mental status, evidence of respiratory muscle fatigue, or unchanged hypoxemia. Most often sedated using ketamine (due to bronchodilatory effects). Vent settings again often rely on decreasing respiratory acidosis and avoidance of “breath stacking.” If breath stacking becomes an issue, then need to change vent settings to allow for longer expiration time. This can be done by decreasing the respiratory rate, decreasing TV, or aiming for I:E ratio 1:4. This will create state of continued elevated pCO2 described as “permissive hypercapnia”  (EM Docs – COPD on the Vent) but will avoid barotrauma and hemodynamic compromise that can occur with “breath stacking.”

Things That Don’t Work in COPD Exacerbation

Methylxanthines (e.g. Theophylline)

Theophylline has shown little efficacy beyond standard treatment of inhaled bronchodilators and steroids in the ED. This meta-analysis of 4 RCTs that included 169 ED patients showed no statistical improvement in admission, length of stay, or ED relapse (British Medical Journal Methylxanthines in COPD (2003)). It was also associated with increased side effects primarily nausea/vomiting, tremor, and anxiousness.

Mucoactive Agents

N-acetylcysteine 600 mg bid showed no statical difference in FEV1, vital capacity, O2 saturation, or subjective breathlessness.

Chest Physiotherapy

Chest physiotherapy showed no significant changes in COPD. However, it has shown evidence in concomitant bronchiectasis if this is present.

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