J Appl Physiol 104: 1241, 2008;
doi:10.1152/japplphysiol.00171.2008
8750-7587/08 $8.00
LETTER TO THE EDITOR
Last Word on Point:Counterpoint: High-frequency ventilation is/is not the optimal physiological approach to ventilate ARDS patients
TO THE EDITOR: It was with great interest that I read the letters to the editor (6) addressing the content of the Point:Counterpoint debate "High-frequency ventilation is/is not the optimal physiological approach to ventilate ARDS patients" (4, 5). The overall issues that were presented across these letters can be summarized as follows. 1) The clinical evidence needed to determine which approach to the management of ARDS is optimal is lacking regardless of the population under discussion. 2) The concept of recruitment/derecruitment injury (R/D, atelectrauma) in ARDS has not been fully appreciated nor integrated in management strategies for ARDS. Here is where HFO historically has had an advantage because of the use of high mean airway pressures presumably above the pressure preventing R/D. However, two recent trials, one in animals (7) and one in patients (2), clearly illustrate how R/D can be avoided in CMV by the use of lung recruitment maneuver followed by the setting of PEEP using a decremental trial. Future comparisons of HFO and CMV need to ensure strategies for both arms are parallel in avoiding injury from R/D. 3) Most of the published randomized controlled trails (RCTs) addressing management of ARDS have not studied the correct group of patients. Many have arrived at this conclusion because of the perceived heterogeneity of the populations of patients studied in these trials. This perception is supported by the results of three trials (3, 8, 9) evaluating the impact of standard ventilator setting on identifying outcome differences in patients already classified as having ARDS by the current American European consensus definition (1). This concern was recently illustrated by Villar et al. (9), who demonstrated that ARDS patients placed on 
0.5 FIO2 and 10 cmH2O PEEP 24 h after meeting ARDS criteria could be separated into three groups with widely varying mortality; ARDS 45.5%, ALI 20%, and acute respiratory failure (P/F > 300 mmHg) 6.3%. The implication being that if an RCT does not account for the varying morality of ARDS patients identified by the current definition, it is possible that an effective therapy could be shown useless or a useless therapy shown effective!
Thus the current debate on the optimal approach (CMV vs. HFO) to the management of ARDS will never be answered appropriately until we establish a better definition of ARDS for the purpose of clinical trials and ensure that the two arms of the study are parallel not just in avoiding volutrauma but also atelectrauma. Until we assure that the patients we study are not heterogeneous with regard to disease severity, we will continue to have negative trials despite overwhelming physiological rationale and convincing animal data. Yes, we need additional appropriately designed RCTs addressing the effect of HFO on outcomes in all patient age groups!
FOOTNOTES
Address for reprint requests and other correspondence: R. M. Kacmarek, Harvard Medical School, Respiratory Care, Massachusetts General Hospital, 55 Fruit St., Ellison 401, Boston, MA 02114 (e-mail: rkacmarek{at}partners.org)
REFERENCES
- Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149: 818–824, 1994.[Abstract]
- Borges JB, Okamoto VN, Matos GFJ, Caramez MPR, Arantes RA, Barros F, Souza CE, Victorino JA, Kacmarek RM, Barbas CSV, Carvalho CRR, Amato MBP. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Am J Respir Crit Care Med 174: 268–278, 2006[Abstract/Free Full Text]
- Ferguson D, Kacmarek RM, Chiche JD, Singh JM, Hallett CD, Mehta S, Stewart TE. Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial. Intensive Care Med 30: 1111–1116, 2004.[CrossRef][Web of Science][Medline]
- Ferguson ND, Slutsky AS. Point: High-frequency ventilation is the optimal physiological approach to ventilate ARDS patients. J Appl Physiol; doi:10.1152/japplphysiol.01226.2007.[Free Full Text]
- Kacmarek RM. Counterpoint: High-frequency ventilation is not the optimal physiological approach to ventilate ARDS patients. J Appl Physiol; doi:10.1152/japplphysiol.01226.2007a.[Free Full Text]
- Muellenbach RM, Wunder Brederlau J C, Villar J, Rotta AT, Maruvada S, Vento G, Tana M, Tirone C, Vendettouli V, Froese A, Bollen CW, Uiterwaal CSPM, van Vught AJ, Lucangelo U, Zin WA, Baumgardner JE, Markstaller K, Otto CM. Comments on Point:Counterpoint: High-frequency ventilation is/is not the optimal physiological approach to ventilate ARDS patients. J Appl Physiol; doi:10.1152/jappphysiol.00153.2008.
- Suarez-Sipmann F, Bohm S, Tusman G, Pesch T, Thamm O, Reissmann H, Reske A, Magnusson A, Hedenstierna G. Use of dynamic compliance for open lung positive end-expiratory pressure titration in an experimental study. Crit Care Med 35: 214–221, 2007.[CrossRef][Web of Science][Medline]
- Villar J, Perez-Mendez L, Kacmarek RM. Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome. Intensive Care Med 20: 930–936, 1999.
- Villar J, Pérez-Méndez L, López J, Belda J, Blanco J, Saralegui I, Suárez-Sipmann F, López J, Lubillo S, Kacmarek RM. An early PEEP/FIO2 trial identifies different degrees of lung injury in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 176: 795–804, 2007.[Abstract/Free Full Text]
Robert M. Kacmarek
Harvard Medical School; and Respiratory Care, Massachusetts General Hospital, Boston, Massachusetts
Copyright © 2008 by the American Physiological Society.
