Treating Failure of Noninvasive Ventilation for Acute Respiratory Failure Due to COPD: Sooner the Better

Over the past 2 decades, use of noninvasive ventilation (NIV) has increased dramatically for both hypoxemic and hypercapnic forms of respiratory failure as well as the two combined. The American Thoracic Society/European Respiratory Society practice guidelines¹ strongly recommend the use of NIV for acute and acute on chronic respiratory failure due to COPD exacerbations. This recommendation stems from robust data including physiologic studies demonstrating reductions in breathing frequency,² dyspnea and work of breathing,³ as well as randomized controlled trials and systematic analyses from over the past 30 years showing reductions in the rate of intubation and mortality.⁴ The success rate of NIV in avoiding intubation and/or death for patients with acute respiratory failure due to COPD exacerbations is very high, from 80–90% in most studies.⁵ However, for the 10–20% who fail, caution is advised to avoid delay of a needed intubation, which is associated with increased mortality.⁶ Although the role of NIV for respiratory failure due to COPD exacerbations has been firmly established, the timing of escalation to intubation in such patients who are failing NIV has not.

As a result, the question of which patients will fail NIV and require early intubation continues to elude researchers. An earlier study had suggested that it was possible to quickly delineate between subjects who fail NIV and those who succeed, as there was a significant difference in the response of subjects’ pH and serum carbon dioxide levels within the first few hours of NIV.⁵ However, the same study also acknowledged that it was difficult to identify which cases would fail NIV late (defined as requiring intubation after 48 h of NIV). Subsequent studies expanded on this, finding risk factors (such as presence of nosocomial pneumonia, increased heart rate, acidosis, hypoxia) in the first few hours of NIV that correlated with late failure of NIV.⁷ There remains a dearth of data on how clinicians can reliably use the above variables and their clinical gestalt to predict the timing of NIV failure earlier in real-world settings, thereby allowing for timely and appropriate escalation of care.

In the current issue of Respiratory Care, Mosher et al⁸ add to the existing data on the importance of timing in the management of NIV failure, using a retrospective cohort of 280 subjects with COPD exacerbations constituting 427 clinical encounters (up to 12 in individual subjects) with NIV in the emergency department prior to admission. Subjects’ data were analyzed for 7 d to determine success (liberation from NIV within 7 d), failure (intubation and/or death within 7 d), or persistence (continued use of NIV at 7 d). In addition, 17 covariates were used in their analysis to identify factors that predict NIV treatment failure.

The authors found that 78% of the 427 clinical encounters were successful, 10% were persistent, and the remainder (12%) experienced NIV failure. Particularly noteworthy was that they found that the median time to failure and success was 8 h and 16 h, respectively; and by 48 h, 81% of failures and 67% of successes had occurred. Lastly, out of the 17 covariates examined, 4 were found to be associated with NIV treatment failure and need for persistent NIV treatment: age, body mass index (BMI), and bicarbonate level.

Strengths of the study include its real-world applicability, pulling in data from a variety of clinical settings, a quaternary university medical center, an academic-affiliated center, and a county hospital, which enhances generalizability. Also, the authors’ use of covariates to identify risk factors for NIV failure is also a strength, as the presence of such factors can be useful when deciding whether and when to escalate care.^9,10 On the other hand, the failure of these covariates to significantly predict treatment failure in the dichotomous analysis must be viewed as a weakness. Other weaknesses include the retrospective design and inevitable missing data; the lack of comparators; and the failure of some of the covariates to associate with NIV failure, such as respiratory rate, which has been identified as a predictor of treatment failure in multiple prior studies. This raises concerns about the reliability of the covariate analysis.

The conclusion that the study highlights the “importance of close clinical monitoring and interval reassessment, particularly within the first 8 h of NIV treatment” is deserving of emphasis but is not novel. Confalonieri et al,¹¹ in 2005, published a chart composed of 4 predictors, blood pH, respiratory rate, Glasgow coma score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score, which enabled prediction of NIV failure or success with 90% accuracy at 2 h after initiation of NIV. They recommended checking these parameters at 2 h and consideration of intubation if the likelihood of failure was high. This illustrates that not only the first 8 h but even the first h or 2 merit close observation and intervention if a patient is declining, to avoid delay of a needed intubation.

Ultimately, studies that observe the timing of interventions and escalations such as initiation of NIV or intubation are examining practice patterns of care teams. These interventions require clinical judgment, and timing depends on interpretation of data and perceptions about when initiation is most likely to be beneficial. The authors’ finding that the median time to NIV failure was 8 h indicates that clinicians at the study institutions were acting quickly to escalate care if they deemed it necessary, in line with the prior recommendations that clinicians avoid delay. However, the study cannot determine what timing is optimal or whether different timing might have yielded better outcomes. In this context, it would be more accurate to say that the current study determined when clinicians recognized NIV failure and decided to intervene rather than when NIV failure per se occurred.

Another notable finding of the study is that although 78% of the subjects succeeded, weaning off NIV within a week, and another 12% failed, either requiring intubation or dying, 10% of the subjects persisted on NIV. Sixty percent of the persistent subjects were on NIV prior to admission, so it would be expected that such subjects would remain on NIV, but 40% were not. As the authors point out, recent guidelines recommend reassessing patients hospitalized with acute hypercapnic respiratory failure 2–4 weeks after discharge to determine whether they should receive long-term NIV.¹² This was based on a single study¹³ that waited 2–4 weeks after discharge before initiating subjects on NIV. This study observed that subjects randomized to NIV had delayed rehospitalization compared to controls using long-term oxygen therapy alone, but the study did not have a comparison group initiated on long-term NIV in the hospital. The persistent group in the current study demonstrates that there may be a subgroup of patients who would benefit from in-hospital initiation of long-term NIV. Such patients might deteriorate after discharge awaiting reassessment, risking increased morbidity and mortality and higher readmission rates.

This study by Mosher et al⁸ underlines the importance of early and close observation of patients being treated with NIV for acute respiratory failure due to COPD and provides some risk factors, advanced age, higher BMI, elevated bicarbonate, and renal dysfunction, that if present would warrant particularly close attention. They also identified a previously underappreciated subgroup of subjects persisting on NIV after a week of hospitalization in whom in-hospital initiation of long-term NIV might be beneficial, but this deserves further study, ideally in a randomized trial.

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