Hospital Practice: Volume 38: No.1

A Primer for the Clinician

Guy W Soo Hoo, MD, MPH

Abstract: Noninvasive ventilation (NIV) has become an integral part of critical care management. Despite > 2 decades of experience, it is relatively underused, with general utilization reported as a little over 10% in a recent international survey. Lack of training, knowledge, equipment, and experience with NIV may account for its slow adoption. Patient selection, staff training and experience, and prompt recognition of ineffective NIV are important components to successful application of NIV. Noninvasive ventilation does have a learning curve that may be steep for some institutions but must be mastered if the procedure is to become a successful institutional component of care. Patients with acute respiratory failure due to chronic obstructive pulmonary disease or congestive heart failure are ideal candidates for NIV, and optimal efficacy in associated conditions is often linked to these 2 conditions. Technical issues and written guidelines are addressed, including details of an adequate trial of therapy as well as criteria for intubation. Attention to these elements should increase the success rate of NIV, which in turn should increase its general use.

Keywords: noninvasive ventilation; chronic obstructive pulmonary disease; congestive heart failure; respiratory failure

More than 2 decades have passed since initial reports of the current iteration of noninvasive positive-pressure ventilation in patients with acute respiratory failure.^1-3 The concept of noninvasive positive-pressure ventilation delivered through a mask interface, using generally ineffective intermittent positive-pressure breathing devices, predates those reports by several decades. After the polio epidemic of the 1950s, invasive ventilatory support through an endotracheal tube and mechanical ventilator became the standard in critical care. Experience with nasal continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea and complications of intubation spurred the development of noninvasive ventilation (NIV). This technique avoided risks associated with endotracheal intubation and complications of the tube and ventilator. As a result of intense interest and investigations, NIV is now an integral and often first-line option in acute respiratory failure.

Despite well-conducted trials and the consensus of professional societies, NIV remains relatively underused.^4-12 This conclusion is supported by a number of investigations, including surveys of indicated and actual use. An optimal utilization rate is an elusive target, varying between institutions because of patient demographics, environment of care, and local expertise. Recent investigations report utilization rates of ~10%, 20% to 25% for most institutions, and > 80% by others.^13-17 Among possible NIV candidates, actual application was believed to be < 50%, but in recent reports, has been found to be only about 33%.^18,19 Successful NIV requires close attention to details of application, since the experience of success or failure often influences its subsequent use. This article reviews the critical elements of successful NIV in adults with acute respiratory distress. Utilization of NIV in pediatric patients and patients with chronic respiratory failure is beyond the scope of this review and not addressed.

The key to successful NIV lies in the recognition of its capabilities and limitations. This, in turn, requires identification of the appropriate patient, staff trained and capable of providing NIV, and prompt determination of unsuccessful NIV to minimize delays in definitive therapy.

First and foremost, certain critically ill patients are better treated with endotracheal intubation and mechanical ventilation, bypassing any trial of NIV. Although such patients could be treated with NIV, it would not be considered a first-line management option. Table 1 provides a list of conditions and circumstances in which NIV should not be considered unless there are other mitigating circumstances.

In addition to clinical features, certain conditions are especially suitable for NIV. A brief review of the pathophysiologic basis of improvement with NIV provides insight into these conditions. Continuous positive airway pressure is noninvasive ventilatory support without augmentation of inspiratory effort, and its benefit in obstructive sleep apnea is a result of “splinting” of collapsible upper airways with positive pressure. Noninvasive ventilation augments inspiratory efforts when provided as pressure support or volume support. Patients with chronic obstructive pulmonary disease (COPD) have an increased respiratory load due to a dynamic hyperinflation and adverse consequences for diaphragmatic strength and exertion. Noninvasive ventilation effectively unloads the respiratory muscles, decreasing transdiaphragmatic pressure, electromyographic activity and work, leading to increases in inspiratory tidal volume, decreasing respiratory rates, PaCO₂, and dyspnea.^20,21 In patients with cardiogenic pulmonary edema (CPE) or severe congestive heart failure (CHF), respiratory failure results from a combination of pulmonary vascular congestion, and interstitial and alveolar edema. Continuous positive airway pressure or NIV with pressure support recruit alveoli collapsed as a result of edema, decrease the work of breathing, and improve ventilation-perfusion relationships. Increasing intrathoracic pressure also decreases preload and afterload, which is beneficial in volume-overloaded patients.²² Noninvasive ventilation is not intended to be sole therapy, but an important adjunct to simultaneously administered treatment. Because decompensated COPD and CHF can be rapidly reversed, they are especially responsive to NIV.

Given the physiology of NIV in COPD or CHF, it follows that other conditions in which the pathophysiology has some basis in COPD or CHF could also be treated with NIV. Table 2 summarizes the clinical conditions best suited for initial treatment with NIV, along with other conditions for which the supporting data are not as robust.

Most experience with NIV has been in patients with COPD exacerbations and hypercapnic respiratory failure, which is also the group best treated with NIV. Although prospective, randomized trials have involved a relatively small number of patients (< 1000), the treatment benefit of NIV in COPD has been consistent in numerous reviews and meta-analyses. Noninvasive ventilation reduces the need for intubation, mortality, complications, and duration of stay. Noninvasive ventilation decreased the intubation rate by 28% (95% confidence interval [CI], 15%–40%), in-hospital mortality rate by 10% (95% CI, 5%–15%), and absolute reduction in length of stay by 4.57 days (95% CI, 2.30–6.38 days).¹⁰ The benefit was greater in more severe COPD exacerbations, defined by an initial pH < 7.30, with intubation rates decreased by 34% (95% CI, 22%–46%), mortality rates reduced by 12% (95% CI, 6%–18%), and absolute reduction in the length of stay by 5.59 days (95% CI, 3.66–7.52 days).¹¹ Patients who were less acidemic (pH > 7.35) did not achieve benefit in these outcome parameters. The severity of respiratory acidosis (pH < 7.25) has been used to identify patients suitable for NIV as failure rates have exceeded 70% at that threshold.²³ However, with increasing NIV experience, successful treatment has been noted with significant CO₂ narcosis, defined as a Glasgow Coma Scale score < 8 and average pH of 7.13 ± 0.06.²⁴

The experience of patients with decompensated CHF or CPE has not been as uniformly in support of NIV, as it has been for patients with COPD. Whereas augmented inspiratory support is crucial for effective assisted ventilation, CPAP is effective in CHF or CPE in the 10-cm H₂O range.²⁵ Experience with the other ventilator modalities, bilevel positive airway pressure (BiPAP), pressure support ventilation, or volume ventilation has been mixed. Reviews or meta-analyses have compared CPAP with these modalities, collectively referred to as NIV.^26,27 Early reports suggesting increased myocardial infarction with BiPAP have not been substantiated.²⁸ Others note improved symptom relief and oxygenation with NIV but no differences in intubation or mortality rates, and benefit only in post hoc analysis involving hypercapnic patients. Meta-analyses do suggest a benefit with CPAP, with a risk reduction in intubation of 60% (risk ratio [RR], 0.40; 95% CI, 0.27–0.58) and decreased mortality of 47% (RR, 0.53; 95% CI, 0.35–0.81). Noninvasive ventilation has a risk reduction in intubation rates of 52% (RR, 0.48; 95% CI, 0.34–0.76), but not mortality rates. No differences were noted when comparing CPAP with noninvasive ventilation.²⁶

The largest randomized trial involved > 1000 emergency room patients with CHF and compared oxygen, CPAP, and BiPAP as adjunctive treatments to conventional therapy.²⁹ There was no intubation or mortality benefit with CPAP or BiPAP. Patients with CPAP and BiPAP had more rapid resolution of symptoms and correction of pH and gas exchange abnormalities compared with the oxygen group. No difference was noted between CPAP and BiPAP. It should be noted that NIV treatment time averaged only 2 hours, ≤ 45% of all patients required intensive care unit (ICU) admissions, and the overall intubation rate for all groups was < 3%. This large study differed from other trials in which patients were managed in an ICU setting and intubation rates for controls were approximately 31%. Thus, whether the results of this trial can be generalized to other critically ill patients is debatable. Nevertheless, NIV is effective in patients with CHF/CPE, with CPAP probably being the more effective mode.

The use of NIV after discontinuation of invasive mechanical ventilation has attracted much interest. Post-extubation respiratory distress and failure can occur in ≥ 20% of patients and reintubation is associated with adverse clinical outcomes. Increasing respiratory load, CHF, upper airway edema, and partial upper airway obstruction have all been implicated as mechanisms leading to respiratory distress.

These results have led to 2 distinct scenarios of NIV use. The first is an early extubation approach for patients who failed weaning trials or did not meet criteria for extubation, who were then extubated to NIV as an adjunct to weaning.^30,31 These patients are still provided ventilatory support, but are no longer encumbered by an endotracheal tube. They can speak, have better preservation of oropharyngeal function, and may avoid complications associated with prolonged intubation and mechanical ventilation. This approach has been the subject of several investigations including a meta-analysis of > 500 (mostly COPD) patients.³² Noninvasive ventilation reduced mortality rates by 45% (RR, 0.55; 95% CI, 0.38–0.79), ventilator-associated pneumonia by 71% (RR, 0.29; 95% CI, 0.19–0.45), weighted duration of ICU stay by 6.27 days (95% CI, 8.77–3.78 days), and hospital days by 7.19 days (10.8–3.58 days) compared with conventional weaning. The duration of endotracheal intubation was reduced by 7.81 days (95% CI, 11.3–4.31 days), as was the need for tracheostomy. Reintubation rates did not decrease. Similar benefits were noted in hypercapnic patients (mostly COPD) who met extubation criteria and were placed on NIV immediately after extubation.³³

The other scenario for NIV use is for patients who meet extubation criteria and are extubated, but then develop respiratory distress.^34,35 This “when needed” NIV support has been associated with increased reintubation rates and mortality. The benefit of NIV in these late application post-extubation trials appears in the COPD patients. Only about 10% of patients in these NIV trials had COPD, which may explain their increased adverse outcomes. Caution is advised when considering NIV for these patients and limiting treatment to COPD patients is a consideration.

The above scenarios represent experience in randomized, prospective studies. Post-extubation NIV has been used in other conditions with success, but may not have undergone or be amenable to prospective randomized trials. Successful extubation of “unweanable” patients with neuromuscular respiratory disease has been reported recently, specifically in patients who were unable to tolerate conventional spontaneous breathing trials or demonstrate acceptable “weaning parameters.”³⁶ These authors reported a 95% successful extubation rate, but > 85% of their patients continued to require some form of long-term assisted ventilation, as might be expected after removal of the endotracheal tube.³⁶

Numerous other conditions have been successfully treated with NIV (Table 2). The success is tempered by limited experience in scope or numbers of patients. As clinicians gain experience with NIV, a stronger endorsement may be possible.

Immunocompromised patients with hypoxemic respiratory failure have been successfully treated with NIV.^37,38 There are reports of patients undergoing solid organ transplantation as well as those with febrile neutropenia and hypoxemic respiratory failure who have been successfully treated with NIV. However, reported trials were limited to single centers involving approximately 50 patients. In solid organ transplants, the subgroup with CPE fared best with NIV. In febrile, neutropenic patients, the severity of illness was relatively modest and NIV was most effective in those with an identified infecting organism treated with targeted antibiotic therapy.

Community-acquired pneumonia is another entity successfully treated NIV. However, the subgroup who fared best with NIV also had underlying COPD.³⁹ Secretions may be a limiting factor in patients with pneumonia given potential difficulties in secretion clearance during face mask ventilation.

Although asthma has a similar obstructive pathophysiology to that of COPD, NIV utilization in patients with asthma has been limited in number and scope. Application has often been in an emergency department setting, with major outcome measures focused on improvement in spirometry and admission, and less emphasis on intubation and hypercapnia.^40,41 Hypercapnia is a late finding in severe asthma, which may account for the relatively low use in this condition.

Postoperative patients, especially after thoracic, cardiac, or abdominal surgery, often experience atelectasis and/or CPE. This problem can be addressed with CPAP, either prophylactically or with the onset of hypoxemia.^42,43 Continuous positive airway pressure is ideally suited for treatment of atelectasis and/or CPE. The clinical benefits of CPAP in the 7.5- to 10-cm H₂O range include lower intubation rates, fewer days in the ICU, and fewer cases of pneumonia.

Patients with advanced disease of any cause or terminal malignancy with established “do not intubate/do not resuscitate” status may also gain some benefit from NIV.^44-46 Use of NIV in terminally ill patients requires careful evaluation of each case, as some patients are unable to tolerate the mask or find it uncomfortable. For some, NIV will only delay the inevitable, but for others it can relieve dyspnea and permit recovery from an acute process. Significant benefit with NIV, including recovery to discharge in ≤ 50% of patients and survival of 6 to 12 months, has been reported. Many of these patients have COPD or CHF, which explains their success with NIV.

Other conditions successfully treated with NIV include decompensated obstructive sleep apnea, obesity-hypoventilation syndrome, and neuromuscular disorders in patients who can manage their secretions either independently or with mechanically assisted coughing.^47,48 Neuromuscular conditions especially suited for NIV are those with hypercapnia and excessive respiratory load or decreased muscle strength or capacity, as occurs in muscular dystrophy, severe kyphoscoliosis, or post-polio syndrome. These represent chronic conditions, but patients may be hospitalized because of acute decompensation. Noninvasive ventilation has also provided ventilatory support to tenuous patients who are undergoing invasive procedures such as percutaneous gastrostomy tube placement.⁴⁹ There will undoubtedly be future reports of successful NIV use in the treatment of other conditions. Those with a component of decompensated COPD or CHF underlying their respiratory distress or failure may fare best with NIV.

Patients with acute respiratory distress syndrome or idiopathic pulmonary fibrosis and severe hypoxemia are not particularly suited for NIV and caution is advised in these conditions.^50,51

In addition to identifying the appropriate condition for NIV, a quick bedside survey will determine if the patient is suitable for NIV. The critically ill are not candidates for NIV; the ideal patient has a condition treatable with NIV and a severity of illness best described as moderate. Patients must be sufficiently cooperative to allow face mask placement, adjustment, and synchronization with the ventilator. In general, agitated, belligerent, and uncooperative patients are not candidates for NIV unless their agitation can be attributed to their respiratory distress. Sedatives are frequently used in intubated patients, but the concern with sedative use in NIV is excessive sedation, blunting of respiratory drive, and respiratory failure requiring intubation. Sedatives may be used judiciously; dexmedetomidine is an option that provides sedation without compromising respiratory drive.^52,53

Severity of illness is a limiting factor in NIV at both extremes of the spectrum. Frank respiratory arrest is an exclusion criterion for NIV, and comatose patients were also once excluded. However, severe hypercapnic respiratory failure with coma due to CO₂ narcosis can respond to NIV. Previous reports suggested limiting NIV to patients with a pH ≤ 7.20 to 7.22, given high NIV failure rates and need for intubation.^7,23 However, comatose, hypercapnic patients with a pH as low as 6.93 have been successfully treated.²⁴ A pH between 7.10 and 7.35 may define the most suitable treatment group. Noninvasive ventilation provides little benefit to COPD patients with mild respiratory distress and pH > 7.35.¹⁰

The importance of nursing and respiratory therapy staff trained and experienced in NIV cannot be underestimated. These elements were critical in investigational trials and may be the main factor limiting current use. When coupled with a lack of physician knowledge and equipment, low expectations or perceptions of NIV create an environment where ineffective NIV becomes a self-fulfilling condition.^15,19 This technology is relatively new and has been in widespread use for only about a decade. Many providers have not received any formal training or may have limited experience with NIV. Initial reports highlighted excess time commitment to NIV patients, undoubtedly a result of lack of training and experience. Subsequent reports do not report excess time required for NIV, but each institution will encounter a staff learning curve for any new NIV program. Possible concerns about infectious transmission during NIV have not been substantiated but, as in any potentially infectious condition, due caution and proper respiratory isolation precautions are advised.⁵⁴

Most patients treated with NIV are treated in ICUs, primarily because of the risk of progressive respiratory failure requiring intubation and mechanical ventilation. Noninvasive ventilation can be provided in a lower-intensity area such as a step-down unit, however, depending on patient severity of illness, potential for intubation, or “do not intubate” status. Specialized units may allow application in an unmonitored ward setting if intubation is not an option.⁵⁵ Almost 40% reported ward NIV use in a recent survey.¹⁹ Emergency departments often have equipment that represents an extension of a critical care unit and, if coupled with appropriate staff, can accommodate the initiation of NIV.⁵⁶ However, this institution-specific situation does not necessarily apply to all emergency departments. Success and expertise gained with NIV in the inpatient setting will only enhance utilization and success in such settings.

Guidelines for NIV usage provide a framework for application, which is especially pertinent in house staff-run institutions with constantly changing personnel. The West Los Angeles Veterans Affairs Medical Center NIV guidelines are presented to illustrate key points in the use of NIV (Figure 1). These guidelines from my own institution provide information on potentially suitable candidates for NIV as well as exclusion criteria. In our medical center, the order for NIV only requires ventilator settings from the physician with mask fitting and troubleshooting, which is the purview of the respiratory therapist.

A properly fitted mask is important for successful NIV as mask leaks and mask intolerance are major causes of NIV failure.^19,57 The default patient-ventilator interface at our institution is an orofacial mask, although nasal masks can be used. For most patients, either mask will be effective, although there can be some individual differences.^58,59 Other patient-ventilator interfaces for NIV include a helmet, whole face mask, nasal pillows, and mouthpiece.¹² The orofacial size is determined by the therapist, using the smallest mask that can fit over the bridge of the nose, extending to the lower mandible, and just covering the vermillion of the lower lips. A mask that is too large will encroach on the chin, resulting in large leaks and ineffective ventilation. Current masks are clear to permit visualization of excess secretion or emesis and are made of materials that permit a better seal while minimizing air leaks and skin pressure. Mask straps are tightened to complete the seal, but should permit passage of 1 to 2 fingers between the straps and face to avoid excessive pressure, as this increases the risk of skin ischemia, necrosis, and pressure ulcers. Foam padding can be applied to pressure points or leak areas to minimize this potential damage. Treatment breaks of 30 to 90 minutes every 3 to 4 hours as tolerated will also help minimize the risk of skin necrosis and pressure ulcers, and provide an opportunity for oral intake by the patient. If treatment breaks are not possible, alternating the type or size of mask may help avoid complications.

If possible, patients can be engaged to assist with NIV application. They should be sitting upright in bed; the mask can be held in place manually with ventilator support delivered while adjustments are made to the mask. Most masks have head gear apparatus that allows for rapid application and removal. While many ventilators have a NIV option, specialty ventilators dedicated to NIV have alarms and leak-adjustment options better suited for NIV, and are often preferred to the critical care ventilator by staff. Adjustments to the ventilator can be made at the bedside based on the patient’s response to initial settings, with adjustments guided by initial and subsequent arterial blood gas results. BiPAP is the most frequently used ventilator mode, although CPAP, volume ventilation, and even proportional-assist ventilation can be effective. Certain conditions can be treated with any of these modes. Some, like CHF, are especially suited for CPAP, whereas the lack of augmented inspiratory support with CPAP would be disastrous in advanced neuromuscular disorders.

Depending on the clinical circumstance, patients may undergo a limited trial of therapy with NIV. Such trials usually last 1 to 2 hours and can help to determine if a patient can be treated with NIV. Numerous investigators have found that significant improvement during a trial of therapy correlates with successful NIV.^57,60-62 Extended trials without significant improvement are not recommended because this only delays intubation and mechanical ventilation (unless patients are “do not intubate” status). Parameters used to gauge the effectiveness of a trial include dyspnea relief, reduction in respiratory rate, or accessory muscle use. Improvement in arterial blood gas abnormalities reflects successful and effective NIV, providing objective evidence of cooperation with NIV and adequate patient-ventilator synchrony. The magnitude of improvement associated with effective NIV is outlined in the guidelines. It is also important to recognize that some patients may have initial improvement with NIV, but eventually fail. This is usually evident in the first 12 to 24 hours of NIV support, but may occur later.⁶² Failure to improve altered sensorium or respiratory acidosis with a 24-hour trial increases the likelihood of NIV failure.

There is a paucity of written guidelines for NIV use.¹⁹ Guidelines are important to provide a standard approach to management.⁶¹ Intubation guidelines are especially important to limit trials in patients who ultimately fail NIV. These intubation criteria often have a subjective element. It is important to recognize these as guidelines since patients may require intubation but not meet any criteria or, conversely, meet criteria for intubation but can be managed with NIV. Table 3 presents guidelines modified from previous investigations to better reflect changes in pH threshold as experience increases with NIV.^5,7

Noninvasive ventilation has a very different profile of complications than endotracheal intubation and mechanical ventilation (Figure 2).^63,64 This difference is due to elimination of the endotracheal tube and associated complications, including direct injury, risks with prolonged intubation, tracheal injury, sinusitis and pneumonia, and sedatives. The main complications related to NIV involve the mask, with associated pressure necrosis and facial ulcers, risk for aspiration of gastric contents during emesis, and drying of mucous membranes. These complications can all be avoided by limiting the use of NIV and providing regular face and oral care. Certain complications are common to both invasive ventilation and NIV, such as barotrauma and nosocomial pneumonia, but occurr much less frequently with NIV.⁶⁵

Noninvasive ventilation has become an important option in the management of critically ill patients. It is underused in most institutions, attributable to a number of factors including lack of knowledge, training, experience, and guidelines. It is important to note that patients with decompensated obstructive lung disease and CHF represent conditions most successfully managed with NIV. Other conditions successfully managed with NIV often involve some element of obstructive lung disease or CHF. Proper patient selection, trained staff, and prompt recognition of the failure of NIV so as not to delay definitive therapy are crucial for its optimal application. While limited to a critical care unit in most institutions, increasing experience may permit its use for selected patients in ward settings.

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