Management of COPD Exacerbations in the ICU: What’s New?
June 1, 2023
By Kathryn Radigan, MD, MSci
Attending Physician, Division of Pulmonary and Critical Care, Stroger Hospital of Cook County, Chicago
Chronic obstructive pulmonary disease (COPD) is predicted to be the fourth leading cause of death in 2030.1 COPD also contributes to significant economic and social challenges, increasing the burden on society. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) identifies a COPD exacerbation as “an event characterized by dyspnea and/or cough and sputum that worsens over ≤ 14 days, which may be accompanied by tachypnea and/or tachycardia and often is associated with increased local and systemic inflammation caused by airway infection, pollution, or other insult to the airways.”2 COPD exacerbations previously were identified as “acute worsening of symptoms that results in additional therapy.” The new definition not only provides more detail, but also separates exacerbation symptoms from treatment, making diagnosis less challenging. Regardless, COPD exacerbations continue to negatively affect health status, including disease progression and mortality, making optimization of the critically ill COPD patient imperative.
Respiratory Support for Inpatient COPD Exacerbations
Oxygen. Supplemental oxygen should be provided to target an oxygen saturation (SpO2) of 88% to 92%.3 Targeted oxygen treatment has been shown to reduce hypercapnia, respiratory acidosis, and mortality.
Noninvasive Ventilation (NIV). NIV is the recommended method of ventilatory support for patients with COPD exacerbations.2 For the majority of patients, bilevel positive airway pressure (BiPAP) is preferred over continuous positive airway pressure (CPAP). NIV improves gas exchange and respiratory acidosis, decreases respiratory rate, improves work of breathing, and reduces complications, including ventilator-associated pneumonia.2 It also reduces need for intubation, length of hospital stay, length of intensive care unit (ICU) stay, and overall mortality.4 It is especially indicated in patients with acute and acute on chronic hypercapnic respiratory failure with an arterial partial pressure of carbon dioxide (PaCO2) of ≥ 45 mmHg and arterial pH ≤ 7.35.4,5 Other indications include severe dyspnea with clinical signs suggestive of respiratory muscle fatigue and/or increased work of breathing and persistent hypoxia despite supplemental oxygen therapy. Contraindications to NIV that should be considered include severely impaired consciousness, facial deformity, high aspiration risk including vomiting, esophageal stenosis, or inability to cooperate, protect the airway, or clear secretions.4
When initiating BiPAP, there are many different approaches that may differ based on patient-specific factors. Many clinicians typically start with 10 cm H2O to 15 cm H2O inspiratory positive airway pressure (iPAP), depending on patient status, and
5 cm H2O expiratory positive airway pressure (ePAP). iPAP is subsequently titrated up as tolerated, usually in increments of 2 cm H2O to a maximum of 20 cm H2O.6 If tolerated, settings are titrated up as needed, but the focus must remain on the driving pressure (iPAP-ePAP) to achieve adequate ventilation. Patients with known or suspected obstructive sleep apnea may need a higher ePAP to adequately ventilate and bypass their obstruction, especially when sleeping. The ePAP also may be increased minimally (e.g., up to 10 cm H2O) for hypoxia, but it is critical to understand the potential effects of this on driving pressure. While on BiPAP, respiratory rate, tidal volume, minute ventilation, work of breathing, mental status, mask leakage, and arterial blood gas (ABG) must be carefully monitored.7
High-Flow Nasal Cannula (HFNC). Although NIV is the optimal method of ventilatory support for those with COPD exacerbations, it typically is not recommended for those with mild exacerbations of COPD without acute hypercapnia.4,8 Thus, HFNC has been considered in the management of mild hypercapnia related to an acute exacerbation of COPD or when patients need a rest from BiPAP. HFNC delivers heated and humidified air-oxygen blends through special devices at rates up to 60 L/min.9 Similar to the success appreciated in patients with acute hypoxemic respiratory failure, HFNC may assist COPD patients by reducing their anatomic dead space, improving ventilation, and mitigating the work of breathing, and it has been shown to benefit stable hypercapnic COPD patients in the home setting.10
Unfortunately, there is no clear consensus on the use of HFNC in COPD exacerbations. One study found that HFNC had no benefit in patients with acute COPD exacerbations with mild hypercapnia (pH ≥ 7.35 and PaCO2 > 45 mmHg) compared to conventional oxygen.11 In contrast, other studies showed significant reductions in respiratory rate, improved PaCO2, and improved oxygen saturation after HFNC treatment in patients with COPD exacerbations.12,13 The European Respiratory Society Clinical Practice Guidelines recommend trialing NIV prior to the use of HFNC in patients with COPD and hypercapnia.8 Regardless, HFNC may be helpful in scenarios in which the patient is not tolerating BiPAP or has a contraindication to BiPAP (e.g., vomiting), but is not critical enough for mechanical ventilation. Further trials are needed to define which patients with acute COPD exacerbations would benefit the most from HFNC.
Tracheal Intubation and Mechanical Ventilation. In general, immediate invasive mechanical ventilation (MV) often is avoided, and NIV is the preferred first step.2 Occasionally, however, there is an immediate need for intubation, which is indicated if the patient is experiencing agonal breathing, cardiopulmonary arrest, concurrent severe hemodynamic instability, life-threatening hypoxia, diminished consciousness, inadequately controlled agitation, massive aspiration, persistent vomiting, inability to remove secretions, and severe arrhythmias.2,14 Forced expiratory volume in 1 second (FEV1), Glasgow Coma Scale score < 11, Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥ 29, respiratory rate ≥ 30, and pH < 7.25 are independent predictors of the need for MV.15,16 In situations where the decision to intubate is not clear, it is best to place the patient on BiPAP while preparing for intubation. Regardless, the clinician will need to optimize the patient’s physiology prior to intubation, and in some scenarios, intubation can be deferred pending the patient’s clinical improvement.
When intubating, it is critical to choose a relatively large size endotracheal tube (ETT).17 A small ETT may lead to increased airway resistance, which may make optimal ventilation challenging. It also is important to ensure slow, gentle bag-valve mask ventilation with a goal of providing adequate time for exhalation. Aggressive bag-valve mask ventilation may lead to pneumothorax or hemodynamic instability due to the development of intrinsic positive end-expiratory pressure (PEEP).
Once the patient is on MV, they should be monitored closely for auto-PEEP, ensuring that end-expiratory flow reaches zero prior to the next breath.18 Auto-PEEP may impair venous return to the heart, leading to hypotension, and also may make it challenging for the patient to trigger the next breath, leading to ventilator dyssynchrony. If the patient is overbreathing to the point of significant auto-PEEP despite setting a lower respiratory rate, sedation may be necessary. Serial arterial blood gases should be monitored with a goal of trying to match the patient’s baseline pCO2.
Weaning from MV. Successful liberation from MV on the initial attempt without the need for reintubation is ideal. A spontaneous breathing trial (SBT) may be conducted using a T-piece or with pressure support ventilation (PSV). Historically, controversy has existed regarding which method is optimal, but data more recently favor PSV even for those patients who are high risk for extubation failure.19,20 Thille and colleagues performed a post-hoc analysis of a multicenter, randomized controlled trial that included equally distributed groups of high-risk patients with underlying chronic cardiac disease or lung disease (including those patients with COPD). Patients were randomized to PSV of 7 cm H2O vs. T-piece.20 PSV trials in critically ill patients at high risk of extubation failure significantly increased the proportion of patients successfully extubated compared to T-piece, without an increased risk of reintubation. In the difficult/prolonged-weaning COPD subgroup, T-piece almost doubled the time to liberation.
After passing an SBT, it often is recommended to extubate to NIV, especially in patients with hypercapnia. In patients with PaCO2 > 45 mmHg before extubation, another study by Thille and colleagues found the reintubation rate at day 7 was significantly lower with NIV with HFNC rather than HFNC alone (8% vs. 21%; difference,−12.9%; 95% confidence interval [CI], −27.1% to −0.1%; P = 0.049).21 Extubating severe COPD patients to NIV, especially those with hypercapnia, therefore, likely is beneficial.
Diagnostic Testing
In patients with acute COPD exacerbations, concurrent life-threatening diagnoses, such as pneumonia, pulmonary embolism, heart failure, pneumothorax, and myocardial infarction, are not infrequent, and additional diagnostic tests need to address these concerns when clinically indicated. All patients should receive a chest X-ray, electrocardiogram (ECG), and basic laboratory tests, along with COVID-19 testing and influenza polymerase chain reaction (PCR) during influenza season.22 ABG is necessary, especially if there is altered mental status or an abnormal venous blood gas with pH < 7.35 or pCO2 > 45 mm Hg. A venous pCO2 < 45 mmHg will reliably exclude arterial hypercarbia, defined as arterial paCO2 > 50 mmHg; however, venous and arterial pCO2 do not correlate closely enough to make additional decisions.23 Point-of-care ultrasound is an additional helpful tool to evaluate for alternative diagnoses as well (e.g., pneumothorax, heart failure).
Pharmacotherapy
Short-Acting Bronchodilators. An inhaled short-acting beta-agonist (SABA), with or without a short-acting muscarinic antagonist (SAMA), is recommended for treatment of COPD exacerbations.5 Although metered dose inhaler (MDI) serves as an effective, convenient, and safe method for delivering bronchodilator aerosols in mechanically ventilated patients when administered with optimal technique, nebulized delivery is preferred in non-ventilated patients, given that acutely symptomatic patients may have difficulty with optimal MDI technique.24 Since SABAs have a more rapid onset of action than the SAMAs, a SAMA-SABA combination or SABA alone is preferred over monotherapy with SAMA. Air-driven nebulization is preferred over oxygen-driven nebulization. It also is recommended to continue the use of inhaled long-acting bronchodilators (either beta-agonist, anticholinergics, or a combination) with or without inhaled corticosteroids (ICS) during an acute exacerbation.2 ICS is recommended especially in patients with frequent exacerbations and elevated blood eosinophils. Bronchodilators can be nebulized and administered in-line through high-flow nasal oxygen or NIV without having to remove the patient from the device.
According to the U.S Food and Drug Administration, albuterol sulfate inhalation solution has been in short supply since fall 2022.25 In February 2023, a major manufacturer, Akorn, ceased operations, severely challenging the already limited supply chain, according to the American Society of Health-System Pharmacists. Around the same time, a number of other pharmaceutical companies revealed shortages as a result of manufacturing issues and/or due to surge in demand. During this shortage, it is recommended for physicians to try to use albuterol MDIs whenever possible. There are adapters for both noninvasive and invasive ventilation to facilitate reliable administration of MDI medication. While there is a substantial shortage, levalbuterol hydrochloride inhalation solution may be used as a replacement to albuterol inhalation solution.26
Glucocorticoids. Systemic corticosteroids are recommended and have been found to improve FEV1 and oxygenation amid shortened recovery time and length of hospitalization.5 They are especially efficacious for patients with peripheral eosinophils. While the GOLD guidelines suggest a five-day course of prednisone, the European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines suggest increasing the range up to 14 days of steroids, if necessary.2,4 Notably, if they are given for longer periods unnecessarily, patients are at increased risk of pneumonia and mortality.27 Both the ERS/ATS and GOLD recommend the administration of oral corticosteroids rather than intravenous (IV) corticosteroids, if gastrointestinal access and function remain intact.4,5 When comparing oral and IV corticosteroids, there was no significant difference in treatment failure, length of hospital stay, readmission rates, or mortality. The typical dose for the majority of patients is prednisone 40 mg to 60 mg once daily, but a higher dose of glucocorticoids occasionally may be used in patients with impending or actual respiratory failure.
Antimicrobial Therapy. Antibiotics, typically prescribed for five to seven days, can shorten recovery time, reduce the risk of relapse, reduce the risk of treatment failure, and shorten hospitalization. Antibiotics should be given to patients who experience dyspnea, an increase in sputum volume, sputum purulence, those who have two of these cardinal symptoms if sputum purulence is one of the two symptoms, or for those requiring NIV or MV.2 Procalcitonin is not recommended to assist in the decision of antibiotics in COPD exacerbation. In ICU patients with COPD exacerbations, the use of a procalcitonin-based protocol led to a higher mortality rate when compared to patients receiving standard antibiotic regimens.28
Local bacterial resistance patterns should guide antibiotic therapy.2 Typical treatment involves an aminopenicillin with clavulanic acid, macrolide, or tetracycline. Patients with COPD exacerbations who typically are at higher risk of resistant organisms include those with frequent exacerbations, severe airflow obstruction with FEV1 < 35%, or exacerbations that require mechanical ventilation. Additional risk factors include those patients who previously have grown resistant organisms, who have had frequent antibiotic prescriptions in the past year, and who have bronchiectasis on imaging. It also is important to test for viruses as a cause of the exacerbation, since antiviral therapy targeting influenza virus or COVID-19 may be warranted.
Magnesium. Intravenous magnesium sulfate with its known bronchodilator effect has long been recommended for severe asthma attacks. It may be associated with improved dyspnea scores, fewer hospital admissions, and reduced length of hospital stay.29 Now it is recommended for use in severe COPD exacerbations, especially in those who are not improving with inhaled bronchodilator therapy.
Bundled Care
Bundled treatments may be of benefit in patients admitted with COPD exacerbations.30 A study by Parikh and colleagues used COPD bundles that included standard nursing protocols, patient education regarding appropriate inhaler technique, and medication options for inhalers, nebulizers, steroids, and antibiotics, along with an additional order set focused on important measures at the time of discharge, including referrals to see outpatient pulmonologists. COPD patients who were treated with bundled care were found to have a significant reduction in mean length of stay, 30-day readmission rates, and 60-day readmission rates. Ninety-day hospital costs were significantly lower in the care bundle group. Additional benefits were more rapid steroid administration, improved pulmonary follow-up, and 100% of COPD patients received inhaler instruction.
Prevention
Long-term prognosis for COPD patients who warrant hospital admission for exacerbations is poor, with a five-year mortality rate of approximately 50%.31 Various outpatient treatment interventions can reduce COPD exacerbations, including bronchodilators, corticosteroid inhalers, and anti-inflammatories such as roflumilast, and long-term macrolides.2 Smoking cessation, pulmonary rehabilitation, lung volume reduction surgery, vitamin D, and interventions such as mask wearing and frequent hand washing also are beneficial. The ERS/ATS guidelines recommend initiation of pulmonary rehabilitation within three weeks of exacerbation, but not during hospitalization.4 Vaccinations, including influenza and pneumococcal vaccinations, also reduce COPD exacerbations. Although many of these measures may be considered on the inpatient side, pulmonary specialty clinic referral should be prioritized and will provide additional benefit for inpatient COPD patients.
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- Kramer N, Meyer TJ, Meharg J, et al. Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 1995;151:1799-1806.
- Oczkowski S, Ergan B, Bos L, et al. ERS clinical practice guidelines: High-flow nasal cannula in acute respiratory failure. Eur Respir J 2022;59:2101574.
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- Xia J, Gu S, Lei W, et al. High-flow nasal cannula versus conventional oxygen therapy in acute COPD exacerbation with mild hypercapnia: A multicenter randomized controlled trial. Crit Care 2022;26:109.
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- Thille AW, Coudroy R, Nay MA, et al. Pressure-support ventilation vs T-piece during spontaneous breathing trials before extubation among patients at high risk of extubation failure: A post-hoc analysis of a clinical trial. Chest 2020;158:1446-1455.
- Santos Pellegrini JA, Boniatti MM, Boniatti VC, et al. Pressure-support ventilation or T-piece spontaneous breathing trials for patients with chronic obstructive pulmonary disease — A randomized controlled trial. PLoS One 2018;13:e0202404.
- Thille AW, Muller G, Gacouin A, et al. Effect of postextubation high-flow nasal oxygen with noninvasive ventilation vs high-flow nasal oxygen alone on reintubation among patients at high risk of extubation failure: A randomized clinical trial. JAMA 2019;322:1465-1475.
- Ko FW, Chan KP, Hui DS, et al. Acute exacerbation of COPD. Respirology 2016;21:1152-1165.
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- Dhand R, Tobin MJ. Bronchodilator delivery with metered-dose inhalers in mechanically-ventilated patients. Eur Respir J 1996;9:585-595.
- American Lung Association. How the albuterol shortage will impact your chronic lung disease. March 13, 2023. https://www.lung.org/blog/albuterol-shortage-lung-health-impacts
- Truitt T, Witko J, Halpern M. Levalbuterol compared to racemic albuterol: Efficacy and outcomes in patients hospitalized with COPD or asthma. Chest 2003;123:128-135.
- Sivapalan P, Ingebrigtsen TS, Rasmussen DB, et al. COPD exacerbations: The impact of long versus short courses of oral corticosteroids on mortality and pneumonia: Nationwide data on 67 000 patients with COPD followed for 12 months. BMJ Open Respir Res 2019;6:e000407.
- Daubin C, Valette X, Thiollière F, et al. Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: A randomized multicenter study. Intensive Care Med 2018;44:428-437.
- Ni H, Aye SZ, Naing C. Magnesium sulfate for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2022;5:CD013506.
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- Hoogendoorn M, Hoogenveen RT, Rutten-van Mölken MP, et al. Case fatality of COPD exacerbations: A meta-analysis and statistical modelling approach. Eur Respir J 2011;37:508-515.
Chronic obstructive pulmonary disease (COPD) exacerbations continue to negatively affect health status, including disease progression and mortality, making optimization of the critically ill COPD patient imperative.
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