Review Author: Son Dang, MD
Introduction
There is recognized evidence associating non-invasive positive pressure ventilation (NIPPV) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) to reduced incidence of endotracheal intubation, however, it remains unstudied at different NIPPV treatment intensities.
In clinical practice, low-intensity NIPPV are commonly used, typically having an inspiratory positive airway pressure (IPAP) of less than 18 cm H2O, whereas high-intensity NIPPV uses pressure-limited ventilation with IPAP levels between 20 to 30 cm H2O to theoretically maximize alveolar ventilation, offset the added dead space of the mask, and reduce inspiratory effort. Here we discuss the HAPPEN trial where the researchers’ investigated patients with AECOPD and persistent hypercapnia after having received 6 hours of low-intensity NIPPV, does high-intensity NIPPV decrease the likelihood of meeting a prespecified criteria for endotracheal intubation?
Study design
Single-blind, multicenter, randomized trial in 30 general respiratory non-ICU wards in China from January 2019 to January 2022. The study population included 300 adults aged ≥ 18 years old (mean age 73 years old, 68% men) with AECOPD, arterial pH of < 7.35, and persistent hypercapnia of > 45 mmHg after receiving 6 hours of low-intensity NIPPV. These patients were randomized to high-intensity NIPPV interventional group (incremental IPAP adjustment to max of 30cm H2O with goal tidal volume of 10-15mL/kg) [n = 147] versus continuing low-intensity NIPPV (IPAP adjustment to max of 20cm H2O with goal tidal volume of 6-10mL/kg) [n = 153].
- Of note, patients in the low-intensity NIPPV group who met the prespecified criteria for intubation were able to crossover to high-intensity NIPPV.
Prespecified criteria for needing endotracheal intubation
1) Arterial pH < 7.25 with PaCO2 that increased by > 20% from baseline or PaO2:FiO2 ratio of < 100 mmHg
2) AND the presence of at least 1 of the following:
o Clinical signs suggestive of severely decreased consciousness (e.g., coma or delirium)
o Accessory respiratory muscle use or thoracoabdominal paradoxical movement
o Excessive respiratory secretions
o Aspiration or emesis
o Bleeding in upper gastrointestinal tract
o Severe hemodynamic instability without response to fluid resuscitation and low-dose vasopressor agents
o Ventricular or supraventricular arrhythmias
3) Or cardiac or respiratory arrest
Discussion
In the high-intensity NIPPV group, 7 patients (4.8%) met the prespecified criteria for needing intubation when compared to 21 patients (13.7%) in the low-intensity group; an absolute difference of -9%. There was no significant difference in the intubate rate during hospitalization between the two groups, likely due to the low-intensity group crossover to high-intensity intervention with 11 out of 13 patients avoiding intubation. The composite outcome of intubation or avoidance of intubation did show a significant difference with 3.4% in high-intensity NIPPV versus 11.1% in low-intensity NIPPV group; absolute difference of -7.7%.
In adverse effects, abdominal distention was more commonly seen in the high-intensity NIPPV group likely due to the higher pressure overcoming the lower esophageal sphincter. Severe alkalosis of pH > 7.55 was also seen in high-intensity NIPPV group, however, without any complicating sequelae noted.
Limitations of the study:
- Early termination of the study after only enrolling only half of the intended participant size due to significant prespecified interim analysis in addition to COVID-19 pandemic interruptions and slower recruitment rates.
- The investigators and treating physicians were not blinded with the possibility for bias in treatment decisions.
- Crossover of low-intensity group to high-intensity intervention reducing the likelihood of group differences in intubation.
- Exclusion of patients with emphysematous bullae or restrictive ventilatory dysfunction (e.g., pulmonary consolidations) limits the generalizability of this study due to possible complications such as development of pneumothorax.
What did this trial show us?
- In patients with AECOPD with persistent hypercapnia following 6 hours of low-intensity NIPPV, escalating treatment to high-intensity NIPPV had significantly less likelihood of meeting criteria for needing intubation. When evaluated for rate of completed intubations during hospitalization, there was no significant difference between the low-intensity and high-intensity NIPPV groups, 3.9% versus 3.4% respectively.
- Of note, the low-intensity NIPPV group had a composite of 11% of those who were intubation or had avoided intubation by crossover to high-intensity intervention, which was significant when compared to high-intensity NIPPV group.
Read the full article here.
References:
1) Luo Z, Li Y, Li W, et al. 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. JAMA. 2024. doi: 10.1001/jama.2024.15815
2) Scott Weingart, MD FCCM. EMCrit 384 – Did this Really Just HAPPEN? – The HAPPEN Trial Hot Take – NIPPV for COPD. EMCrit Blog. Published on September 29, 2024. Accessed on November 16th 2024. Available at [https://emcrit.org/emcrit/happen-trial/ ].