The cornerstone of treatment for severe exacerbations of chronic obstructive pulmonary disease remains non-invasive positive pressure ventilation. Typically, this involves bi-level positive pressure settings, preventing alveolar collapse while assisting with inspiration and gas exchange. This works – most of the time. When it doesn’t work – endotracheal intubation.
This trial, the HAPPEN trial, looks at a little bit different approach. If typical BIPAP settings aren’t working, why not just IPAP harder?
In this unblinded, randomized-controlled trial, patients with acute exacerbations of COPD received traditional NIPPV with inspiratory pressures <18 cmH20 or “high-intensity” NIPPV, with airway pressures titrated up to 20-30 cmH20. The equipoise from this trial comes from a body of literature in which this “high-intensity” treatment paradigm has been used to improve respiratory physiology on an intermittent, outpatient basis. Extending these data to the acute setting, these authors aimed to use “high-intensity” NIPPV in an attempt to decrease rates of endotracheal intubation.
As per the authors report, the trial was a “success” – indeed, such a “success” it was stopped early for benefit. Among the ~150 patients in each arm, those randomized to “high-intensity” NIPPV improved their primary outcome of “need for endotracheal intubation” – 4.8% in the “high-intensity” cohort (IPAP settings of ~25 cmH2O) versus 13.7% in the “low-intensity” cohort (IPAP settings of ~18 cmH2O). These observations were durable in both unadjusted and adjusted results, as well as across most pre-specified subgroups.
However, “need for endotracheal intubation” was not the same as “received endotracheal intubation” – “need for endotracheal intubation” was a composite outcome of worsening acidosis, worsening clinical status, or respiratory arrest. In actuality, the number of patients intubated in each group were the same – 3.4% and 3.9% in each group. Crossover from “low-intensity” to “high-intensity” was permitted, however, and may have reduced the number of “low-intensity” patients requiring intubation. However, the unblinded nature of the trial confounds a bit of interpretation of the influence of the crossover event. There were more safety and adverse outcomes associated with the “high-intensity” cohort, with “abdominal distension” and intolerance of NIPPV the most frequent safety excess, and “severe alkalosis” the most frequent “serious adverse event”.
While this seems an interesting and plausible idea for treating COPD, this trial has almost-zero applicability to the emergency department. Patients enrolled in this trial were effectively “subacute” COPD inpatients whose length of illness was a median of 6 days at time of enrollment, had already been on “low-intensity” NIPPV for at least six hours, had near-normal mean pH of 7.31, and mean respiratory rate of 22 at time of randomization. These were, effectively, stable-but-not-fully-improved inpatients at a small risk for further deterioration, not the acute respiratory distress seen in the ED.
This is still an interesting idea, though, and there is likely equipoise to test NIPPV with higher inspiratory pressures in the ED. Tidal volumes, dyspnea scores, and accessory muscle use were all superior at higher IPAP settings, and may confer benefit in the acute setting. That said, I would not implement this practice without sufficient evidence from an ED setting, as the signals of IPAP intolerance may be as problematic in a patient-oriented sense as the perceived physiologic advantages.
“Effect of High-Intensity vs Low-Intensity Noninvasive Positive Pressure
Ventilation on the Need for Endotracheal Intubation in Patients With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease”
https://jamanetwork.com/journals/jama/article-abstract/2823763