Noninvasive positive pressure ventilation: Increasing use in acute care

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Rapid improvement in cardiogenic pulmonary edema, but possibly no lower mortality rate

The Three Interventions in Cardiogenic Pulmonary Oedema (3CPO) trial,28 with 1,156 patients, was the largest randomized trial to compare NIPPV and standard oxygen therapy for acute pulmonary edema. It found that NIPPV (either CPAP or noninvasive intermittent positive pressure ventilation) was significantly better than standard oxygen therapy (through a variable-delivery oxygen mask with a reservoir) in the first hour of treatment in terms of the dyspnea score, heart rate, acidosis, and hypercapnia. However, there were no significant differences between groups in the 7- or 30-day mortality rates, the rates of intubation, rates of admission to the critical care unit, or in the mean length of hospital stay.

In contrast, several smaller randomized trials and meta-analyses showed lower intubation and mortality rates with NIPPV.29,30 Factors that may account for those differences include a much lower intubation rate in the 3CPO trial (2.9% overall, compared with 20% with conventional therapy in other trials), a higher mortality rate in the 3CPO trial, and methodologic differences (eg, patients for whom standard therapy failed in the 3CPO trial received rescue NIPPV).

If NIPPV is beneficial in cardiogenic pulmonary edema, the mechanisms are probably its favorable hemodynamic effects and its positive end-expiratory pressure (PEEP) effect on flooded alveoli. Specifically, positive intrathoracic pressure can be expected to reduce both preload and afterload, with improvement in the cardiac index and reduced work of breathing. 31,32

Notwithstanding the possible lack of impact of NIPPV on death or intubation rates in this setting, the intervention rapidly improves dyspnea and respiratory and metabolic abnormalities and should be considered for treatment of cardiogenic pulmonary edema associated with severe respiratory distress. A subgroup in which the NIPPV may reduce intubation rates is those with hypercapnia.33 A concern that NIPPV may increase the rate of myocardial infarction34 was not confirmed in the 3CPO trial.28 Interestingly, there were no differences in outcomes between CPAP and noninvasive intermittent positive pressure ventilation in this setting.28,34,35

Immunocompromised patients with acute respiratory failure

A particular challenge of NIPPV in immunocompromised patients, particularly compared with its use in COPD exacerbation or cardiogenic pulmonary edema, is that the underlying pathophysiology of respiratory dysfunction in immunocompromised patients may not be readily reversible. Therefore, its application in this group may need to follow clearly defined indications.

In one trial,20 inclusion criteria were:

  • Immune suppression (due to neutropenia after chemotherapy or bone marrow transplantation, immunosuppressive drugs for organ transplantation, corticosteroids, cytotoxic therapy for nonmalignant conditions, or the acquired immunodeficiency syndrome)
  • Persistent pulmonary infiltrates
  • Fever (temperature > 38.3°C; 100.9°F)
  • A respiratory rate greater than 30 breaths per minute
  • Severe dyspnea at rest
  • Early hypoxemic acute respiratory failure, defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (Pao2/Fio2 ratio) less than 200 while on oxygen.

Compared with patients who received conventional treatment, fewer of those randomized to additional intermittent noninvasive ventilation had to be intubated (46% vs 77%, P = .03), suffered serious complications (50% vs 81%, P = .02), or died in the intensive care unit (38% vs 69%, P = .03) or in the hospital (50% vs 81%, P = .02).

Similarly, in a randomized trial in 40 patients with acute respiratory failure after solid organ transplantation, more patients in the NIPPV group than in the control group had an improvement in the Pao2/Fio2 ratio within the first hour (70% vs 25%, P = .004) or a sustained improvement in the Pao2/Fio2 ratio (60% vs 25%, P = .03); fewer of them needed endotracheal intubation (20% vs 70%, P = .002); fewer of them died of complications (20% vs 50%, P = .05); they had a shorter length of stay in the intensive care unit (mean 5.5 vs 9 days, P = .03); and fewer of them died in the intensive care unit (20% vs 50%, P = .05). There was, however, no difference in the overall hospital mortality rate.36


NIPPV has been used to treat respiratory failure after extubation,22,37 to prevent acute respiratory failure after failure of weaning,38–41 and to support breathing in patients who failed a trial of spontaneous breathing.42–45

Unfortunately, the evidence for using NIPPV in respiratory failure after extubation, including unplanned extubation, appears to be unfavorable, except possibly in patients with chronic pulmonary disease (particularly COPD and possibly obesity) and hypercapnia. An international consensus report stated that NIPPV should be considered in patients with hypercapnic respiratory insufficiency, especially those with COPD, to shorten the duration of intubation, but that it should not be routinely used in extubation respiratory failure.46

Treatment of respiratory failure after extubation

Two recent randomized controlled trials compared NIPPV and standard care in patients who met the criteria for readiness for extubation but who developed respiratory failure after mechanical ventilation was discontinued. 22,37 Those two studies showed a longer time to reintubation for patients randomized to NIPPV but no differences in the rate of reintubation between the two groups and no difference in the lengths of stay in the intensive care unit.

Of greater concern, one study showed a higher rate of death in the intensive care unit in the NIPPV group than in the standard therapy group (25% vs 14%, respectively).22 This finding suggests that NIPPV delayed necessary reintubation in patients developing respiratory failure after extubation, with a consequent risk of fatal complications.

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