Spare the Tube, Save a Life

This is part of a recurring series examining landmark articles in Emergency Medicine, in the style of ALiEM’s 52 Articles.


Brochard, L. Mancebo, J. Wtsocki, M. et al. “Noninvasive Ventilation for Acute Exacerbations of Chronic Obstructive Pulmonary Disease.” NEJM 1995, 333(13):817-22.

Main Points:

  1. In this randomized prospective multicenter trial of 85 patients admitted to ICUs throughout Europe with COPD exacerbations, noninvasive ventilation reduced the need for endotracheal intubation, length of stay and in-hospital mortality rate.
  1. 31 of the 42 patients in the standard arm required intubation, compared to 11 of 43 patients in the noninvasive arm (p<0.001). These results were consistent among the five centers studied. The mortality rate and length of stay was similar in the two groups in whom endotracheal intubation was required, suggesting that the benefits observed in noninvasive ventilation resulted from lower rates of intubation.
Figure 1. Mask used to deliver noninvasive ventilation

Figure 1. Mask used to deliver noninvasive ventilation


COPD exacerbations often manifest as acute hypercapnic ventilatory failure and endotracheal intubation can be a life-saving procedure. This intervention, however, is not without associated risks both during the time of the procedure as well as later in the course of the patient’s care. This patient population is at risk for hemodynamic compromise during intubation and may be difficult to manage on the ventilator due to a multitude of concerns including air trapping and tachypnea. The risk for ventilator associated pneumonia and other complications secondary to being intubated for prolonged periods of time are also worth considering.

Brochard and his colleagues investigated the use of noninvasive ventilation in COPD exacerbations in hopes of reducing mortality through the reduction of intubation. Thiswas a multicenter prospective randomized study that recruited patients in five European ICUs. The primary and secondary outcomes were patient-centered and this article from 1995 has clearly framed the manner in which we manage the sick COPD patient today. The medications used and manner in which noninvasive ventilation is employed has evolved since the publication and a comprehensive review of management was published in 2010 by the American Academy of Family Physicians. ACEP also has published clinical guidelines on use of noninvasive ventilation in 2010.


This prospective multicenter study enrolled 85 out of 275 patients admitted to the ICU with COPD or a high probability of the disease based on careful history, physical examination and chest x-ray. Patients were selected if they had a respiratory acidosis and elevated bicarbonate level. Additional criteria included dyspnea for less than two weeks and at least two of the following: respiratory rate >30 BPM, partial pressure of arterial O2 <45 mm Hg, arterial pH <7.35 after the patient was breathing room air for at least 10 minutes. The exclusion criteria included: respiratory rate <12 BPM, need for immediate intubation-defined by strict criteria in the paper, already intubated, use of sedative drugs in the past 12 hours, CNS disorder, cardiac arrest in the past five days, cardiogenic pulmonary edema, neuromuscular or skeletal disorder, upper airway obstruction or asthma, clear cause of decompensation requiring treatment, or facial deformity. Patients were either assigned to the standard arm which included treatment with: maximum of 5LPM O2 by nasal prongs with goal O2 saturation >90%, medications such as subcutaneous heparin, antibiotic agents and bronchodilators (subcutaneous terbutaline, aerosolized or intravenous albuterol, corticosteroids or intravenous aminophylline), correction of electrolytes. The noninvasive arm received the same medications with the addition of periods of noninvasive ventilation. The same apparatus was used at all five sites to deliver pressure support of 20 cm H20 with an expiratory pressure that was atmospheric. Patients underwent noninvasive ventilation for at least six hours a day with overall duration determined by clinical criteria and arterial blood gal levels.

In order to standardize care, the authors created major and minor criteria as objective markers for the need to perform endotracheal intubation. The major criteria included: respiratory arrest, respiratory failure with LOC or gasping for air, psychomotor agitation making nursing care impossible and requiring sedation, HR<50 BPM with loss of alertness, hemodynamic instability with SBP <70 mm Hg. There was a series of minor criteria also relating to vital sign instability, mental status changes or arterial pH <7.3. In both groups the presence of one major criterion was an indication for intubation. After the first hour of treatment the presence of two minor criteria was an indication for intubation.

Patients were evaluated at the one hour, three hour and 12 hour mark following the initiation of therapy. The primary outcome examined was the need for endotracheal intubation with secondary end points including length of stay, complications not present on admission (pneumonia, barotrauma, gastrointestinal hemorrhage, renal insufficiency, neurologic events and pulmonary embolism), duration of ventilatory assistance, and mortality rate during hospitalization. 31 of the 42 patients in the standard arm required intubation, compared to 11 of 43 patients in the noninvasive arm (p<0.001). Per the authors, these results were consistent among the five centers studied, however, examining table 2 sites one and two seemed to have high percentages of intubation, 100 and 83 percent respectively, compared to the others. This may be skewed by the overall low numbers studied. Patients who ultimately were intubated both in the standard and noninvasive arms had extended ventilation time with 17 +/- 21 days and 25 +/- 17 days respectively. Complications and events leading to death are shown in Table 4.

Level of Evidence:

This study was graded a level I based on the ACEP Clinical Policy Grading Scheme for therapeutic questions.


The use of pressure support of 20/0 is quite different from the manner in which many providers initiate noninvasive ventilation today. This may be secondary to the limitations of the technology at the time because the photograph in figure 1 (see above) displays a mask that appears different from what you find on modern machines.

Relevant articles:

Ahn, J. Pillow, T. “Focus On: Noninvasive Positive Pressure Ventilation in the Emergency Department.” 2010,—Practice-Management/Focus-On–Noninvasive-Positive-Pressure-Ventilation-In-the-Emergency-Department/

Evensen, A. “Management of COPD Exacerbation.” Am Fam Physician 2010, 81(5): 607-13.

Faculty Reviewer: Dr. Siket

Source Articles:

Brochard, L. Mancebo, J. Wtsocki, M. et al. “Noninvasive Ventilation for Acute Exacerbations of Chronic Obstructive Pulmonary Disease.” NEJM 1995, 333(13):817-22.

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