Noninvasive ventilation for Acute COPD Exacerbations

In Review

Brochard L, et al. "Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease". New England Journal of Medicine. 1995. 333(13):817-822.
PubMed • Full text

Clinical Question

In patients with acute exacerbations of chronic obstructive pulmonary disease, does noninvasive ventilation decrease the need for endotracheal intubation?

Bottom Line

Noninvasive positive pressure ventilation (NPPV) in acute exacerbation of COPD decreases the need for endotracheal intubation and decreases mortality, complications, and length of stay.

Major Points

This study expands on an earlier prospective trial by Bott et al in 1993 that measured a mortality reduction, but did not excluded all patients that could not tolerate NPPV. This study further expands on the previous by measuring hospitalization length of stay, complications of hospital stay, and avoidance of endotracheal intubation in patients receiving NPPV plus standard care over standard care alone for Acute COPD Exacerbations. After this trial, these measured benefits became common endpoints for COPD related studies.

While the authors do not provide statistical power data, confidence intervals, or large sample size, the study did provide statistically significant benefit in mortality on NPPV (9% vs 12%), decreased length of stay by about 10 days, and a lower composite risk of in-hospital complications including complications inherently greater in intubation such as pneumonia, barotrauma, and sepsis. Importantly, the physiologic parameters such as arterial pH and blood gas and clinical parameters such as respiratory rate and encephalopathy were improved measurable faster than in standard care.

Guidelines

• 2004 NICE guidelines recommend NPPV for persistent hypercapnic ventilatory failure exacerbations not responding to medical therapy alone.

• 2013 GOLD guidelines recommend NPPV in patients respiratory acidosis or respiratory distress with signs of muscle fatigue.

Design

• Multicenter, open-label, blinded randomization, parallel-group, prospective trial
• N=85
  • Standard treatment (n=42)
  • Noninvasive ventilation (n=43)
• Setting: 5 centers in Western Europe
• Enrollment: September 1990 - November 1991
• Mean follow-up: Not reported, per-protocol follow-up is hospital stay + 3 months
• Analysis: Not reported
• Primary outcome: Need for intubation during study

Population

Inclusion Criteria

• Diagnosis of COPD or high probability of COPD based on clinical history, physical exam, chest imaging
• Respiratory acidosis with elevated bicarbonate level
• Exacerbation of dyspnea lasting less than two weeks and at least two of the following:
  • Respiratory rate above 30 breaths per minute
  • Partial pressure of arterial oxygen below 45 mm Hg
  • Arterial pH below 7.35

Exclusion Criteria

• Respiratory rate less than 12 breaths per minute
• Immediate need for intubation (respiratory arrest, respiratory pauses with loss of consciousness or gasping, psychomotor agitation, hemodynamic instability)
• Tracheotomy or intubation prior to admission
• Administration of sedative medications in the 12 hours prior
• CNS disorder unrelated to hypercapnic encephalopathy or hypoxemia
• Cardiac arrest in the last 5 days
• Cardiogenic pulmonary edema
• Chronic respiratory failure resulting from other conditions (kyphoscoliosis, neuromuscular disorder, upper airway obstruction, asthma)
• Patients who refused intubation

Baseline Characteristics

For the NIPPV arm vs intubation:

• Demographics: Age 71 years vs 69 years
• Vitals: SBP 143 vs 145, HR 105 vs 107, RR 35 vs 33
• Encephalopathy Score: 1.8 vs 1.6
• Laboratory data at admission: PaO2 41 vs 39, PaCO2 70 vs 67, pH 7.27 vs 7.28, bicarbonate 33 vs 32, Hgb 14.5 vs 13.8
• 10% vs. 12% of patients had prior mechanical ventilation episodes

Interventions

• Randomized to CPAP at least 6 hours per day + standard treatment or standard treatment
• Standard treatment included 5 lpm nasal cannula, subcutaneous heparin, antibiotics, bronchodilators, electrolyte correction
• Bronchodilators included SC tertbultaline, albuterol (aerosol and intravenous), corticosteroids, IV aminophylline

Outcomes

Comparisons are NPPV with standard treatment vs standard treatment

Primary Outcomes

Need for endotracheal intubation

26% vs. 74% p < 0.001

Secondary Outcomes

Length of hospital stay

23 ± 17 days vs 35 ± 33 days

Complications not present on admission

16% vs. 48% p = 0.001

Duration of ventilatory assisstance in those requiring intubation

25 days vs 17 days

Mortality during hospital stay

9% vs. 29% p = 0.02

Subgroup Analysis

Affect of intubation on death

No signficant mortality difference between groups after controlling for endotracheal intubation

In those responding to noninvasive ventilation, there was a statistically significant improvement in respiratory rate, PaO2, PaCO2, encephalopathy score, and SAPS score

Criticisms

• Patients highly selected for COPD exacerbation with a clear cause limited total enrollment, only 31% of those screened.
• The rate of intubation in usual treatment is too high (74%) implying sub-optimal standard care regimen.
• The limitation of oxygen delivery to 5 lpm by nasal cannula may be responsible for increased intubation when venturi facemask and higher O2 delivery is preferred.
• Less than expected proportion of patients in both groups received corticosteroids and sympathomimetics; none received anticholinergic treatment. These factors may contribute to sub-optimal care.
• The authors did not disclose which treatments were administered by aerosol or intravenous which complicates the interpretation of their effect on the primary endpoint.
• The study excluded those who needed intubation on presentation to the hospital
• The time on noninvasive positive pressure ventilation was limited and there was no allowance for change of ventilation mode in those failing initial settings.

Funding

Funding by Institut National de la Santé Et de la Recherche Médicale (INSERM)