Chronic Obstructive Pulmonary Disease

Acute exacerbations of chronic obstructive pulmonary disease (COPD) traditionally carried a high mortality rate—up to 33% of patients admitted to the hospital died despite appropriate therapy. Patients with COPD have an expiratory airflow limitation owing to the collapse of small and medium-sized airways. When patients have acute exacerbations of COPD, they have difficulty with gas exchange and therefore retain carbon dioxide. Historically, the treatment of acute exacerbations of COPD consisted of the administration of bronchodilators, systemic corticosteroids, supplemental oxygen, and antibiotics. When all measures failed, patients were intubated and mechanically ventilated. Mortality rates and the frequency of intubation for patients with hypercapnic respiratory failure decreased once NIV became an option for treatment.

For patients with acute exacerbations of COPD, NIV is one of the most effective treatments to improve patient outcome. The mortality benefit of NIV has been assessed in a number of randomized controlled trials. A Cochrane review evaluated 10 studies that looked at patient mortality when NIV was used for COPD exacerbations. There was a significant benefit, with a number needed to treat (NNT) of just 10 to improve the mortality rate.

With the development of NIV, practitioners recognized that using this therapy before patients reach the extremes of respiratory distress obviated the need for endotracheal intubation in many cases. The same Cochrane review examined the role of NIV to prevent endotracheal intubation in respiratory failure from COPD and found an NNT of just 4. One in 4 patients was spared the need for sedation and invasive mechanical ventilation, which decreases the likelihood of a variety of ventilator-associated conditions that increase patient morbidity. Other outcomes shown to improve with the early application of NIV for COPD exacerbations include decreased hospital duration of stay, decreased complications, and improvements in pH, respiratory rate, and partial pressure of carbon dioxide in arterial blood (Pa co ₂ ). BPAP was the primary mode of NIV in the studies examined by this Cochrane review. No high-quality studies have evaluated CPAP for COPD. Recent guidelines on the use of NIV support the use of BPAP for patients with COPD and pH of less than 7.35. NIV in the form of BPAP should be started early in the treatment of ED patients with acute COPD exacerbations.

Acute Cardiogenic Pulmonary Edema

Exacerbation of acute congestive heart failure resulting in ACPE is a leading cause of ARF in EDs in the United States. The in-hospital mortality rate for patients with ACPE can be as high as 12%. A growing body of literature supports the use of NIV in patients with ACPE.

In patients with or without existing cardiomyopathy, increased left ventricular end-diastolic pressures cause the left atrium to pump against an increased load. As the atrium becomes overwhelmed, an increased hydrostatic pressure gradient is created within the pulmonary arterial and venous systems. Eventually, the pulmonary interstitium becomes overloaded, resulting in alveolar collapse and widening of the area reserved for diffusion of gases. Therapy for ACPE is aimed at reducing cardiac preload, reducing afterload, removing excess volume, and recruiting areas of lung with V/Q mismatch.

Initial studies on the use of NIV for ACPE were performed in the 1930s; however, subsequent investigations shifted focus to more invasive ventilatory strategies. It was not until the publication of several case series in the 1970s that interest in NIV for ACPE resurfaced. Clinical practice guidelines now strongly recommend the use of NIV for ACPE. Similar to patients with acute COPD exacerbations, patients presenting with ACPE have a lower mortality rate when NIV is initiated early in their management. A Cochrane systematic review and metaanalysis found an NNT of 13 to improve mortality when NIV was compared with standard therapy for ACPE. Interestingly, when CPAP and BPAP were compared individually with standard therapy, only CPAP demonstrated a statistical improvement in mortality (with an NNT of 9). In contrast, when the metaanalysis compared CPAP with BPAP, no difference was found in the mortality rate. Although the current literature is more robust for CPAP, EPs should feel comfortable initiating either CPAP or BPAP for patients with ACPE. It might be reasonable to choose a NIV modality based on the presence of hypercapnia. Patients with ACPE and hypercapnia both have better outcomes with BPAP, and patients with ACPE without hypercapnia will see the consistent benefits of CPAP. The authors favor the use of BPAP in patients with ACPE and hypercapnia, whereas patients with ACPE without hypercapnia may derive benefit from CPAP.

In addition to mortality, NIV has been shown to improve other outcomes in patients with ACPE. A Cochrane review of 22 trials found a decreased rate of endotracheal intubation (NNT of 8), decreased the length of stay in the intensive care unit, and decreased respiratory rate among patients receiving NIV. Interestingly, there were no improvements in heart rate, systolic blood pressure, diastolic blood pressure, or mean arterial pressure. There had been concern that BPAP, compared with CPAP, might increase the incidence of acute myocardial infarction in patients with ACPE, but recent reports do not support this association.

Asthma Exacerbations

Given the similarities between asthma and COPD with respect to obstructive airway pathophysiology, it seems logical that NIV would improve outcomes in patients with acute exacerbations of asthma. However, no studies have demonstrated improved morbidity or mortality rates from the use of NIV in patients with asthma.

Asthma is a disease marked by the pathologic triad of airflow obstruction, mucus hypersecretion, and bronchoconstriction. Exacerbations of asthma can be caused by infection, medication nonadherence, environmental allergens, and exposure to cigarette smoke. Treatment of the patient with an acute asthma exacerbation centers on the administration of inhaled bronchodilators and systemic corticosteroids. Additional therapies that can be considered include intramuscular bronchodilators, magnesium sulfate, helium–oxygen admixture, and NIV.

There is a dearth of literature on the use of NIV in acute asthma exacerbations. A 2012 Cochrane review on NIV for acute asthma exacerbations states that “this course of treatment remains controversial.” A 2011 clinical practice guideline from the Canadian Critical Care Trials Group “make(s) no recommendation about the use of noninvasive positive-pressure ventilation in patients who have an exacerbation of asthma, because of insufficient evidence.” No randomized trial has evaluated the use of CPAP in asthma patients. Three small, randomized trials evaluated BPAP in asthma. Holley and colleagues compared 19 patients placed on BPAP for asthma with 16 patients who received standard therapy. None of the patients in this study died; 1 patient in the BPAP group and 2 in the control group required intubation. The study was stopped early owing to poor enrollment. In the second study, Soroksky and colleagues compared BPAP with standard therapy in 15 patients. No patients died or were intubated. In the third study, Soma and colleagues analyzed 26 patients who received BPAP compared with 14 patients in a control arm. No patients died or were intubated.

Although the benefit of NIV in asthma has not been demonstrated in large, multicenter randomized trials, no demonstrable harm from this intervention has been detected. Its routine use cannot be recommended, but, in select cases of severe asthma, NIV should be considered.

Traumatic Respiratory Failure

Patients with blunt chest injury are at high risk for respiratory failure. In the trauma patient, endotracheal intubation and mechanical ventilation are associated with high rates of ventilator-associated pneumonia and prolonged use of mechanical ventilation. Observational trials and several small, randomized studies have assessed the use of NIV in blunt chest trauma, yielding mixed results. A 2013 systematic review concluded that the early use of NIV in blunt chest trauma could be considered. This recommendation is based on 1 medium-sized randomized trial that had improved rates of intubation in patients with chest trauma and hypoxemia (ratio of arterial oxygen partial pressure to fractional inspired oxygen [P/F ratio] <200) when managed with NIV compared with a nonrebreather mask. Patients who develop respiratory failure later in their course (after 48 hours) are unlikely to benefit from NIV, so its use is not recommended. Select patients with thoracic trauma who have hypoxic respiratory failure within the first 48 hours after trauma might benefit from BPAP. The available evidence does not support NIV as rescue therapy in patients with chest trauma who develop respiratory failure.

Community-Acquired Pneumonia

There is great interest in using NIV for patients with community-acquired pneumonia (CAP) to avoid the complications of invasive mechanical ventilation. Unfortunately, the literature on NIV for patients with CAP has produced mixed results. Prospective trials have demonstrated failure rates as high as 50%. Studies that demonstrated lower rates of intubation with NIV in CAP primarily included patients who had less severe disease and responded to initial medical therapy. A single, randomized, controlled trial evaluating standard therapy and standard therapy plus NIV in 56 patients with CAP found no improvement in the mortality rate. Patients who received NIV did have lower rates of intubation and shorter lengths of stay in an intermediate care unit. An additional randomized, controlled trial evaluated patients with ARF of varying causes. In this study, patients with CAP who were treated with NIV had lower intubation rates and a lower mortality rate in the intensive care unit.

Results from additional studies have demonstrated less favorable results, causing confusion about the role of NIV in patients with respiratory failure from CAP. As a result of the ambiguity in evidence, current guidelines do not provide a recommendation about the use of NIV in CAP. If it is used, patients with less severe disease who show an early response to therapy might achieve benefit from NIV. It should be used with caution in patients with CAP.

Immunocompromised Patients

Treatment of ARF in the immunocompromised patient is fraught with difficulty. Immunosuppressed patients are at high risk for infectious complications of endotracheal intubation and mechanical ventilation. In a cohort of solid organ transplant patients with respiratory failure, Antonelli and colleagues demonstrated decreased rates of intubation and mortality in the intensive care unit in patients randomized to NIV compared with standard therapy. Hilbert and colleagues compared NIV with standard therapy in immunocompromised patients with pneumonia. Patients who received NIV for 3 hours, followed by a 3-hour period without NIV, had fewer intubations and decreased mortality. More recent data from a multicenter database of patients with hematologic malignancies demonstrated similar mortality rates between patients treated initially with NIV and those treated initially with mechanical ventilation. Importantly, more than 50% of patients treated initially with NIV did not require intubation. Based on the available evidence, NIV guidelines recommend the use of BPAP in immunosuppressed patients with pneumonia. It is important to recognize that the rate of NIV failure is higher for this patient population compared with other diseases, such as exacerbations of COPD and ACPE.

Delayed Sequence Intubation

Endotracheal intubation of the critically ill patient with hypoxia is difficult and fraught with the potential for morbidity and mortality. Some practitioners use NIV after sedation to recruit areas of lung with shunt physiology to improve the chance of successful endotracheal intubation without further hypoxia. A prospective case series in the ED setting describes the successful application of this technique in patients presenting with acute hypoxic respiratory failure. Misinterpretation of this technique has led some to view it as a way to avoid intubation. It should be emphasized that this approach to the patient in respiratory failure is not meant as a way to avoid intubation, but as a mechanism to provide safer conditions for it. If the patient fails to improve or worsens, the clinician should be ready to perform immediate intubation; if the patient improves, a more controlled intubation can be attempted.