Correspondence

Noninvasive Ventilation in Immunosuppressed Patients

N Engl J Med 2001; 344:2027-2028June 28, 2001

Article

To the Editor:

Hilbert and coworkers (Feb. 15 issue)1 report that immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure who were treated with noninvasive ventilation had a lower rate of endotracheal intubation, a lower rate of serious complications, and a lower mortality rate in the intensive care unit than patients who received standard care. We question whether oxygen supplementation with a Venturi mask represents an adequate standard of care for this group of patients. In a previous study,2 the authors reported on the merits of continuous positive airway pressure (CPAP) in a similar population of patients. It is surprising that the authors chose to revert to a lower standard of care in this new study.1

The adequate control group for this study should have been patients who were treated not with standard care but with CPAP and lung physiotherapy. Oxygen supplementation alone may worsen acute respiratory failure by increasing the risk of atelectasis.3 Furthermore, although this is controversial, there might be an increased risk of oxygen-induced toxicity in patients who undergo chemotherapy.4 The use of oxygen supplementation alone to treat patients who have acute respiratory failure is not standard care.

Waheedullah Karzai, M.D.
Egbert Hüttemann, M.D.
University Hospital, 07740 Jena, Germany

4 References

1. 1

   Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med 2001;344:481-487
   Full Text | Web of Science | Medline

2. 2

   Hilbert G, Gruson D, Vargas F, et al. Noninvasive continuous positive airway pressure in neutropenic patients with acute respiratory failurerequiring intensive care unit admission. Crit Care Med 2000;28:3185-3190
   CrossRef | Web of Science | Medline

3. 3

   Dantzker DR, Wagner PD, West JB. Instability of lung units with low V̇_A/Q̇ ratios during O₂ breathing. J Appl Physiol 1975;38:886-895
   Web of Science

4. 4

   Rinaldo J, Goldstein RH, Snider GL. Modification of oxygen toxicity after lung injury by bleomycin in hamsters. Am Rev Respir Dis 1982;126:1030-1033
   Web of Science | Medline

To the Editor:

We are concerned about the accuracy of the measurements of the fraction of inspired oxygen (FiO₂) and therefore of the ratio of the partial pressure of arterial oxygen (PaO₂) to FiO₂ in the study by Hilbert et al. Control patients received oxygen through a Venturi mask, presumably with a directly attached Venturi apparatus. This device, originally developed by Campbell,1 was designed to limit FiO₂ in patients with chronic obstructive pulmonary disease and thus prevent the cycle of oxygen-induced hypoventilation compounded by further increases in FiO₂ as the inspiratory flow rate decreased. It sets an upper limit but does not ensure a precise FiO₂.

If the inspiratory flow rate of the acutely ill patients in the study exceeded the flow rate of the Venturi mask, the FiO₂ was overestimated. In patients with stable pulmonary function, the inspiratory flow rate averages 30 liters per minute.2 The maximal inspiratory flow rate can exceed 200 liters per minute. For acutely ill patients with a respiratory rate of 35, minute ventilation approaching 20 liters per minute, and a ratio of inspiration to expiration of 1:3, the inspiratory flow rate approaches 80 liters per minute. Clearly, the inspiratory flow rate and the FiO₂ of patients who were breathing oxygen through a Venturi mask are unknowns in the study. By contrast, the ventilators used in the standard-treatment group deliver an FiO₂ that is close to the targeted amount. If some control patients were intubated because the FiO₂ was overestimated and the PaO₂:FiO₂ ratio was underestimated, this would constitute a flaw in the study design. If the term “Venturi mask” was used to indicate another device with a more precise FiO₂, it would be important to document the actual FiO₂ delivered, since the PaO₂:FiO₂ ratio was the main criterion for intubation that portended an adverse outcome.

Barry A. Gray, M.D.
Gary T. Kinasewitz, M.D.
University of Oklahoma College of Medicine, Oklahoma City, OK 73190

2 References

1. 1

   Campbell EJM. A method of controlled oxygen administration which reduces the risk of carbon-dioxide retention. Lancet 1960;2:12-14
   CrossRef | Web of Science | Medline

2. 2

   Tobin MJ, Chadha TS, Jenouri G, Birch SJ, Gazeroglu HB, Sackner MA. Breathing patterns. II. Diseased subjects. Chest 1983;84:286-294
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Karzai and Hüttemann state that treating patients who have acute respiratory failure with oxygen supplementation alone is not standard care and that CPAP should be systematically used in such patients. CPAP is widely used. Nevertheless, to our knowledge, although several studies have shown the ability of the method to improve hypoxemia, only one randomized study has demonstrated that the use of CPAP reduces the need for endotracheal intubation in patients with severe hypercapnic cardiogenic pulmonary edema.1 In fact, respiratory failure of cardiac origin and hypercapnia with acidosis were exclusion criteria in our study. Delclaux et al. have recently reported that, as compared with standard oxygen therapy, CPAP neither reduced the need for intubation nor improved outcomes in patients with acute hypoxemic nonhypercapnic respiratory insufficiency.2 Concerning the risk of oxygen-induced toxicity, we assume that CPAP must be used with oxygen in patients with hypoxemia and, thus, it could not prevent this risk.

We share the concern of Gray and Kinasewitz about the risk of underestimation of the PaO₂:FiO₂ ratio when oxygen is delivered through a Venturi mask. Error in the FiO₂ setting must be considered, especially because the PaO₂:FiO₂ ratio was used in most studies of acute respiratory failure and noninvasive ventilation. Nevertheless, the risk of error in the FiO₂ setting applies to all oxygen-delivery systems. How can one estimate the FiO₂ when oxygen is administered through a nasal cannula? In the study by Alsous et al.,3 each liter of oxygen delivered through a nasal cannula was assumed to add 3 percent oxygen to room air. We assume that the modifications in the respiratory rate, the ratio of inspiration to expiration, and the inspiratory flow rates could also affect FiO₂ in this and other oxygen-delivery systems.

A fault in the FiO₂ setting can be verified by obtaining an independent, direct measurement of FiO₂. But which method should be used? Should a sampling catheter be placed in the nasopharynx to allow the measurement of the end-tidal oxygen fraction? Should a gas analyzer be connected to this catheter or simply to the inside of the mask? Recommendations are needed for further prospective, controlled studies.

A Venturi mask was also used in another study4 and in both prospective, controlled studies in immunosuppressed patients. Thus, despite the risk of underestimation of the PaO₂:FiO₂ ratio, the use of the same oxygen-delivery system facilitates comparisons between studies.

The possibility of an error in the FiO₂ setting does not constitute a flaw in the study design: noninvasive ventilation was used in a sequential mode, and in the majority of cases, the decision to intubate was made when the patients were not receiving ventilation. Thus, in terms of the decision to intubate, the estimation of the PaO₂:FiO₂ ratio was the same in both groups of patients.

Gilles Hilbert, M.D.
Didier Gruson, M.D.
Fréderic Vargas, M.D.
University Hospital, 33076 Bordeaux CEDEX, France

4 References

1. 1

   Bersten AD, Holt AW, Vedig AE, Skowronski GA, Baggoley CJ. Treatment of severe cardiogenic pulmonary edema with continuous positive airway pressure delivered by face mask. N Engl J Med 1991;325:1825-1830
   Full Text | Web of Science | Medline

2. 2

   Delclaux C, L'Her E, Alberti C, et al. Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: a randomized controlled trial. JAMA 2000;284:2352-2360
   CrossRef | Web of Science | Medline

3. 3

   Alsous F, Amoateng-Adjepong Y, Manthous CA. Noninvasive ventilation: experience at a community teaching hospital. Intensive Care Med 1999;25:458-463
   CrossRef | Web of Science | Medline

4. 4

   Antonelli M, Conti G, Rocco M, et al. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 1998;339:429-435
   Full Text | Web of Science | Medline