American Journal of Respiratory and Critical Care Medicine

In the early 1990s, noninvasive ventilation (NIV) emerged as a potential useful addition in the management of patients with ventilatory failure due to an acute exacerbation of chronic obstructive pulmonary disease (COPD). That it was an effective alternative to standard medical therapy and oxygen (1, 2), and indeed to endotracheal intubation and mechanical ventilation (3), was confirmed in a number of randomized controlled trials (RCTs), systematic reviews, and meta-analyses (4). A reduction in infectious complications was a consistent finding, and in some studies this translated into reduced ICU and hospital lengths of stay. Cost is one barrier to the implementation of any new treatment in medicine. However, NIV was more cost effective than standard therapy (5) and the savings were even greater when performed outside the ICU (6). In enthusiastic units, as confidence and skill grows, outcomes improve and NIV can be used in sicker patients and lower-dependency settings. Despite this overwhelming evidence that NIV is more effective than standard therapy and can be provided at lower cost, the technique has been underutilized.

In this issue of the Journal, Chandra and coworkers (pp. 152–159) report the pattern and outcomes of NIV use for acute exacerbations of COPD between 1998 and 2008 (7). It was only in 2008 that NIV overtook invasive mechanical ventilation as the most frequently used form of support in these patients. What are the main reasons for the “late adoption” of NIV? One survey performed in the United States (8) identified lack of physician knowledge as the main reason, followed by inadequate staff training and poor previous experiences. The importance of these “human” factors underscored the need for more education and training, as experience and confidence with the technique are important for NIV success. Geographical reasons may also explain the inhomogeneous pattern of NIV utilization around the world. In Europe NIV seems to be more popular than it is in North America (9), at least for treating COPD exacerbation. This may be due to the fact that the first RCTs were performed in France (1) and in the United Kingdom (2), and under the direct responsibility of a physician in ordering and directly applying NIV with the support of all the staff, including nurses and respiratory therapists, while in the United States the prescription is ordered by the M.D., but it is “independently” applied by the respiratory therapist; this practice may alter the concept of teamwork. The motivation of physicians, respiratory therapists, and nurses is one of the keys for success. A lack of enthusiasm or belief in the technique by any one professional group will impede implementation. The equipment available may also be important. In the early studies ICU ventilators, not designed to deliver NIV and with poor leak compensation (10), or simple machines designed primarily for use in the patient's home (2), were used. Practitioners familiar with intensive care ventilators with sophisticated monitoring may be uncomfortable with the simple ventilators designed for home use, which provide very little real-time information about delivery of ventilation or patient–ventilator interaction. The relatively poor performance of ICU ventilators or the lack of monitoring may each have contributed to worse outcomes, and therefore a lack of confidence in the technique. Ventilators, with sophisticated algorithms and real-time monitoring displays, specifically designed for the delivery of NIV in the acute setting, are now available. There is also a much wider range of interfaces available, making it easier to find something that suits an individual patient.

A recent audit from the United Kingdom raises significant concerns about the practice of NIV in the “real” world (11). Data were collected on 9,716 patients. Twenty percent of those with gases recorded on admission were acidotic and another 6% developed acidosis later in their admission. Nearly one-third of the patients with the greatest evidence base for effectiveness did not receive NIV. Patients who became acidotic later in their admission had a worse prognosis. Of greatest concern, for a comparable pH, patients receiving NIV had a worse outcome than those treated with conventional therapy. These data suggest poor understanding of the indications for NIV and its implementation, highlighting again the importance of training and education.

The study by Chandra and colleagues gives us other important information. First, in the time frame considered the overall mortality for COPD exacerbation decreased significantly, and this is particularly important in the largest group of patients, those not receiving any form of ventilatory support. This suggests that there have been significant advances in the management of hospitalized patients with acute exacerbations of COPD during this time. It is difficult to see exactly what these are, as the medical therapy for an acute exacerbation (steroids, antibiotics, nebulized bronchodilators, and oxygen therapy) has been unchanged for considerably longer. More appropriate use of oxygen may be a factor, but even recent audits have shown that there is still a tendency to overoxygenate these patients. A recent RCT from Australia has shown that this is clearly harmful (12). Better chronic disease management, particularly increased uptake of pulmonary rehabilitation, which has been shown to increase the speed of recovery from an acute exacerbation, may be a more important factor.

Second, there was a significant increase over time in the percentage of patients over 75 years of age undergoing NIV. This is not surprising, since life expectancy has increased in recent years, together with the incidence and prevalence of COPD. Most of the RCTs comparing NIV and standard medical treatment enrolled much younger patients, but a recent RCT performed in patients older than 75 years confirmed the benefits in these patients (13).

Third, it was reported that contrary to the overall favorable trends, mortality was high and increasing over time in the small subset of patients (∼5% of those treated with NIV) needing to be transitioned from NIV to invasive ventilation, especially older patients. This is partially in contrast with the results obtained by Demoule and coworkers (14), who showed that NIV failure was independently associated with ICU mortality in the patients developing hypoxemic respiratory failure de novo group, but not in the COPD group. Among the possible explanations suggested by Chandra and colleagues in the Discussion for the discrepancy between the two studies are differences in severity of the patients and/or the time elapsed between the start of NIV and the transition to invasive ventilation. This may be particularly important; several studies have shown that persisting with NIV despite lack of improvement may delay the time to intubation unduly, thereby increasing mortality. An alternative explanation is that patients who fail NIV form a poor prognostic group. Failure is not homogeneous. Some patients will fail because of problems with the application of or tolerance for the interface; these will tend to fail early, and the substitution of a different interface, namely an endotracheal tube, will improve the delivery of effective ventilation. Others will fail because they are difficult to ventilate. When applied well, NIV has the same physiological effect as invasive ventilation, and it is difficult to see how patients who are tolerating the interface with good synchronization with the ventilator and adequate inflation pressures will benefit from intubation. These patients will tend to fail later, and this time may be usefully spent preparing the patient and their family and moving to a more palliative approach, rather than escalating therapy. Finally, patients may fail because of poor application of NIV. The appropriate response, then, is to recognize the problems and correct them, rather than intubate the patient. When patients fail early, there is still time for medical therapy to work and a reason to buy some time with ventilatory support. When it occurs later, this will be despite medical therapy, and there is less that is potentially reversible. This explains the worse outcome in patients developing acidosis during their admission in the British audit (11) and those patients who deteriorate later after an initial response to NIV (15).

Fourth, the study of Chandra and coworkers showed that the charges for hospitalization and the length of hospital stay were significantly lower in the NIV group versus the invasive ventilation group, confirming earlier studies and highlighting the need for a better system of reimbursement compared with the high DRG obtained when a patient is intubated.

As stated by Chandra and colleagues, the study also has several limitations (such as the use of the ICD-9 classification) and the lack of any data about the patients’ status (such as arterial blood gases, the presence of co-morbidities, and the initial response to NIV). There are other aspects such as the appropriateness of the initial treatment (16) (i.e., patients not needing any support, but enrolled for an NIV trial), the kind of interfaces and ventilators used, and last but not least, the environment in which NIV was applied, that may also have determined the final outcomes of the patients.

NIV has become both the “gold standard” and “standard of care” for most patients with an acute exacerbation of COPD of sufficient severity to require ventilatory support. Important challenges remain in the ongoing education and training of healthcare workers responsible for the prescription and delivery of NIV. The respiratory community needs to determine the most appropriate response when patients develop acidosis during their admission or deteriorate despite NIV. For some patients escalation in therapy is the right response, but for others a move to a more palliative approach is more appropriate.

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