Computer-driven Protocolized Weaning from ... - ATS Journals

968

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 175 2007

We have developed an array of recombinant A. fumigatus allergens and tested their diagnostic value in A. fumigatus– sensitized patients suffering from allergic asthma or CF. The aim of these studies was to confirm ABPA suspected from clinical signs and not to provide an alternative diagnosis method. The rationale behind a discriminatory property of some recombinant allergens like MnSOD (Asp f 6) is that they are expressed only during the late phase of A. fumigatus germination (4) and are therefore unlikely to be seen by the immune system of A. fumigatus– sensitized individuals without ABPA. In contrast, secreted allergens like Asp f 1 are seen by the immune system of all exposed individuals and therefore potentially able to induce an IgE immune response in all atopic individuals (5). Because the fungus is able to produce more that 80 allergens (6), it cannot be expected that all A. fumigatus–sensitized patients mount an IgE response against all allergens, limiting the sensitivity of a diagnosis based on single molecules. A further complication related to the serology of ABPA is that the A. fumigatus–specific IgG and IgE levels vary depending on the stage of the disease. Therefore, patients with ABPA should be stratified according to the phase of the disease for a correct diagnosis (7). If this stratification is taken into account, the diagnosis of ABPA based on recombinant allergens is quite reliable and highly specific, but the sensitivity never reaches 100%. From the 65 patients with asthma analyzed by Giavina-Bianchi, only 26 are RAST positive to A. fumigatus and, therefore, at potential risk to develop ABPA. The majority of the patients, 39 subjects, do not show any A. fumigatus–specific IgE RAST and are consistently negative if tested for IgE against the recombinant allergens. They would not be considered as A. fumigatus– sensitized in normal allergy screening. Among the 26 RASTpositive patients, 19 (70%) developed an IgE response against recombinant allergens, a figure similar to other studies performed with recombinant A. fumigatus allergens. We do not know the reason for the discrepancy between the skin prick test and A. fumigatus–specific RAST observed by Giavina-Bianchi. However, as pointed out by Greenberger (3), in patients with asthma only proximal bronchiectasis (in the absence of distal bronchiectasis) and elevated A. fumigatus–specific serum IgE and IgG are specific criteria for the diagnosis of ABPA. Therefore, elevated serum IgE and a positive skin test to the fungus should be demonstrated before considering ABPA as a possible reason for pulmonary complications in patients with asthma or CF. Conflict of Interest Statement : Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

Reto Crameri Swiss Institute of Allergy and Asthma Research (SIAF) Davos, Switzerland Richard Kraemer University of Berne Berne, Switzerland References 1. Kraemer R, Delose´a P, Ballinari P, Gallati S, Crameri R. Effect of allergic bronchopulmonary aspergillosis on lung function in children with cystic fibrosis. Am J Respir Crit Care Med 2006;174:1211–1220. 2. Nelson LA, Callerame ML, Schwartz RH. Aspergillosis and atopy in cystic fibrosis. Am Rev Respir Dis 1979;120:863–873. 3. Greenberger PA. Allergic bronchopulmonary aspergillosis and fungoses. Clin Chest Med 1988;9:599–608. 4. Schwienbacher M, Israel L, Heesemann J, Ebel F. Asp f6, an Aspergillus allergen specifically recognized by IgE from patients with allergic bronchopulmonary aspergillosis, is differentially expressed during germination. Allergy 2005;60:1430–1435.

5. Crameri R. Molecular cloning of Aspergillus fumigatus allergens and their role in allergic bronchopulmonary aspergillosis. Chem Immunol 2002; 81:73–93. 6. Kodzius R, Rhyner C, Konthur Z, Buczek D, Lehrach H, Walter G, Crameri R. Rapid identification of allergen-encoding cDNA clones by phage display and high-density arrays. Comb Chem High Throughput Screen 2003;6:147–154. 7. Patterson R, Greenberger PA, Radin RC, Roberts M. Allergic bronchopulmonary aspergillosis: staging as an aid to management. Ann Intern Med 1982;96:286–291.

Computer-driven Protocolized Weaning from Mechanical Ventilation To the Editor:

We read with interest the recent article by Lellouche and colleagues in which they show that a computer-driven weaning protocol, as compared with human-controlled weaning guidelines, significantly reduces duration of mechanical ventilation and length of stay in the intensive care unit (1). The authors deserve compliments for their efforts. Although it has been shown to be difficult to test the efficiency of protocols in randomized controlled trials (2), the investigators were very successful in this respect. We agree with them that a computer-driven weaning protocol will become the future of weaning. Indeed, adherence to weaning protocols can be disappointingly low, even if caregivers are well trained (3). Despite the clear presentation of results, some questions remain. The so-called “comfort zone,” as clearly defined in the computer-driven weaning protocol, may differ strongly from what was accepted as “comfortable” in the human-controlled weaning guidelines. In the computer-driven weaning arm, “comfort” was defined as having a respiratory rate between 15 and 30 breaths/min, a tidal volume above a minimum threshold (⬎ 300 ml, ⬎ 250 ml if weight ⬍ 55 kg), and an end-tidal CO2 below a maximal threshold. Only when these criteria were met was the support adapted to a lower level until minimal levels were reached. In the control arm, “comfort” was only minimally defined. In fact, the attending physician had to decide whether the patient was “comfortable enough” to adapt support to lower levels. Of course, this difference is in fact part of what is being compared, but we hypothesize that this part may be larger than expected. For instance, even with a respiratory rate between 15 and 30 breaths/min, the physician may have decided not to lower the support level in case the breathing pattern gave the impression that the patient was “uncomfortable.” In addition, no data are given on tidal volumes used in this study during the weaning process. Indeed, no target tidal volumes were given in the human-controlled weaning guidelines, while with computer-driven weaning only the minimal threshold of tidal volumes was set. Lung-protective mechanical ventilation using lower tidal volumes has been found to benefit patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) (4). Of note, it is advisable to use lower tidal volumes throughout the period of mechanical ventilation, that is, also during weaning. Although we are not informed about the incidence of ALI/ARDS in the study by Lellouche and coworkers, we assume a majority of their patients must have suffered from ALI/ARDS. From experience, we know physicians are reluctant to use lower tidal volumes (5), in particular because their use may result in higher respiratory rates. Given these questions, can the authors provide us with data on tidal volumes and respiratory rates in the two arms of the study? Conflict of Interest Statement : L.M.K. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.J.S. has participated as a speaker in scientific meetings or courses organized and financed by

Correspondence

969

various pharmaceutical companies (Maquet, Hamilton, Eli Lilly); he received €1,000 in 2006 for speaking at conferences sponsored by Maquet; he received $12,500 in 2005 and 2006 from Hamilton as research grants for performing a mono-center clinical trial; another Hamilton-sponsored grant is pending.

Liesbeth M. Kager Marcus J. Schultz Academic Medical Center Amsterdam, The Netherlands References 1. Lellouche F, Mancebo J, Jolliet P, Roeseler J, Schortgen F, Dojat M, Cabello B, Bouadma L, Rodriguez P, Maggiore S, et al. A multicenter randomized trial of computer-driven protocolized weaning from mechanical ventilation. Am J Respir Crit Care Med 2006;174:894–900. 2. Rubenfeld GD. Just a spoonful of technology makes the protocol go down. Am J Respir Crit Care Med 2006;174:849–851. 3. Ely EW, Bennett PA, Bowton DL, Murphy SM, Florance AM, Haponik EF. Large scale implementation of a respiratory therapist-driven protocol for ventilator weaning. Am J Respir Crit Care Med 1999;159:439–446. 4. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301–1308. 5. Wolthuis EK, Korevaar JC, Spronk P, Kuiper MA, Dzoljic M, Vroom MB, Schultz MJ. Feedback and education improve physician compliance in use of lung-protective mechanical ventilation. Intensive Care Med 2005;31:540–546.

criteria allowed the inclusion of patients with PaO2 /FiO2 below 200. Interestingly, at inclusion, 15 patients (20.3%) in the computerdriven weaning and 16 patients (22.9%) in the control group (p ⫽ 0.706) had a PaO2/FiO2 ratio ⬍ 200 mm Hg. This shows that patients with quite low levels of PaO2 /FiO2 can be managed with the system. However, the system should be used in patients who demonstrate improving respiratory condition, with stable hemodynamic and neurological status, and not at the time a patient is developing ARDS. In particular, the sytem is not designed to maintain tidal volume at a fixed level. Conflict of Interest Statement : F.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. L.B. has received research contracts with Drager Medical for the conduct of clinical trials concerning the studied system, approximately €15,000 per year from 2001 to 2004. Drager Medical has provided the equipment necessary for the study, including EVITA 4 ventilators equipped with the Evita Weaning System, and has provided a grant necessary to cover insurance costs, Ethics Committee’s administrative fees, and organization of meetings for the investigators and for monitoring purposes. L.B. has received approximately €10,000 in 2006 as royalties from Drager.

Franc¸ois Lellouche Hoˆpital Henri Mondor Cre´teil, France and Centre de recherche de l’Hoˆpital Laval Que´bec, Canada Laurent Brochard Hoˆpital Henri Mondor Cre´teil, France

From the Authors: References

We first would like to thank Drs. Kager and Schultz for their interest in our recent article (1). Their first comment concerned the different definitions of the “comfort zone” between the study and control groups. During the weaning process, the target zone for the respiratory rate as indicated in the written guidelines of the different centers slightly differed: 25–35 breaths/min and clinical comfort (Cre´teil), 25–30 breaths/min and an adequate adaptation to the ventilator (Barcelona), or below 30 breaths/min with a tidal volume ⭓ 6 ml/kg (Geneva). This is, however, what was indicated in the guidelines available in these centers, and there is a possibility that it substantially differed from what was really applied in clinical practice. Our goal was to study the efficacy of the system in centers with interest in the topic of weaning, as reflected by written guidelines, and having a reasonable level of staffing, but we did not try to assess the real life application of these guidelines in each center. The other point raised concerned the tidal volumes used in both arms. We did not record tidal volumes in the two arms after inclusion and cannot fully address this question. At inclusion, tidal volumes were 574 ⫾ 129 ml in the computerized weaning group and 554 ⫾ 142 ml in the control group (p ⫽ 0.402). Interestingly, patients could be included who had an SpO2 above or equal to 90% and FiO2 below or equal to 50%. These

1. Lellouche F, Mancebo J, Jolliet P, Roeseler J, Schortgen F, Dojat M, Cabello B, Bouadma L, Rodriguez P, Maggiore S, et al. A multicenter randomized trial of computer-driven protocolized weaning from mechanical ventilation. Am J Respir Crit Care Med 2006;174:894–900.

Erratum: “In the Beginning” of COPD: Is Evolution Important? From the Editor:

There was an error in the name of the author of the editorial “‘In the Beginning’ of COPD: Is Evolution Important?,” which was published in the March 1 issue of the AJRCCM (1). First and last names were inverted. The correct form of the name is: Nikos M. Siafakas, M.D., Ph.D. We apologize for the error. Edward Abraham Editor References 1. Siafakas NM. “In the beginning” of COPD: is evolution important? Am J Respir Crit Care Med 2007;175:423–424.