Correspondence
Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury
N Engl J Med 2000; 343:812-814September 14, 2000
- Article
To the Editor:
The Acute Respiratory Distress Syndrome Network investigators (May 4 issue)1 deserve commendation for their important study. Because of its importance and despite the clarity of the results, several points should be made.
First, this study was not simply a comparison of high and low tidal volumes, but rather a comparison of two distinct and highly specific strategies of ventilatory management, with differences in tidal volume and airway pressure. Use of positive end-expiratory pressure was specified by the protocol, and on days 1 and 3 of the study, the group treated with lower tidal volumes had significantly higher positive end-expiratory pressure than did the group treated with traditional tidal volumes. The authors state that the benefit occurred “despite” the higher positive end-expiratory pressure. In reality, much laboratory evidence and the results of at least one clinical study2 suggest that lung recruitment, provided in part by positive end-expiratory pressure, is protective and may actually be necessary for lung protection when the tidal volume is reduced.
Second, the authors suggest that hypercapnic acidosis (accompanying reduced tidal ventilation) is deleterious, and the study involved the buffering of acidosis with intravenous bicarbonate. The authors appear to attribute the improved outcome to the nonstandardized partial buffering of hypercapnic acidosis. We are concerned about the suggestion that low levels of hypercapnic acidosis are deleterious, given the accumulating evidence that acidemia in general,3 and hypercapnic acidosis specifically,4 may have beneficial effects. Furthermore, there is evidence that the buffering of acidosis has adverse effects in experimental studies of lung injury.5
Third, the authors often point to between-group differences in mean values (e.g., the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, positive end-expiratory pressure, pH, and partial pressure of arterial carbon dioxide) as evidence of cause and effect. Many of these associations might be better demonstrated by multivariate analyses or an assessment of frequency intervals rather than by simple comparisons of group means.
Our comments refer only to the interpretation of the data and to extrapolation therefrom. The primary outcomes speak for themselves and constitute an important, and clear, message.
5 ReferencesJohn G. Laffey, M.B.
Brian P. Kavanagh, M.B.
Hospital for Sick Children, Toronto, ON M5G 1X8, Canada1
The Acute Respiratory Distress Syndrome Network
Full Text | Web of Science | Medline2
Amato MBP ,Barbas CSV ,Medeiros DM , et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998;338:347-354
Full Text | Web of Science | Medline3
Hood VL ,Tannen RL . Protection of acid-base balance by pH regulation of acid production. N Engl J Med 1998;339:819-826
Full Text | Web of Science | Medline4
Laffey JG ,Kavanagh BP . Carbon dioxide and the critically ill -- too little of a good thing? Lancet 1999;354:1283-1286
CrossRef | Web of Science | Medline5
Laffey JG ,Engelberts D ,Kavanagh BP . Buffering hypercapnic acidosis worsens acute lung injury. Am J Respir Crit Care Med 2000;161:141-146
Web of Science | Medline
To the Editor:
The study by the Acute Respiratory Distress Syndrome Network demonstrates convincingly that the survival of patients with acute lung injury is improved by a protective strategy of mechanical ventilation. The authors attribute the lower mortality rate in the group treated with lower tidal volumes to reduced ventilator-associated lung injury. However, information on the immediate causes of death is not provided. Since death may be attributable to extrapulmonary organ failure rather than to the failure of pulmonary gas exchange, reduced lung injury may not sufficiently explain the improved outcome.
Another possible explanation for the lower mortality rate in the group treated with lower tidal volumes is improved systemic oxygen delivery. Systemic oxygen delivery depends not solely on pulmonary gas exchange but also on cardiac output and intact organ microcirculation. Reduced inspiratory airway pressure in patients receiving low tidal volumes may increase cardiac output and diminish the need for exogenous vasopressor drugs. Decreased use of these drugs would improve microvascular organ perfusion. The article does not provide data on cardiovascular function and the administration of vasopressor drugs.
Pressure-controlled ventilation with decelerating inspiratory flow limits inspiratory airway pressure similarly and may deliver higher tidal volume.1 This approach may optimize alveolar ventilation and improve the elimination of carbon dioxide. As a consequence, pressure-controlled ventilation may allow for lower respiratory rates than those used in the present study and, hence, for a further reduction in inspiratory airway pressure at a constant respiratory volume per minute, with concomitant increases in cardiac output and systemic oxygen delivery.
1 ReferencesLudwig Ney, M.D.
Wolfgang M. Kuebler, M.D.
University of Munich, D-81366 Munich, Germany1
Al-Saady N ,Bennett ED . Decelerating inspiratory flow waveform improves lung mechanics and gas exchange in patients on intermittent positive-pressure ventilation. Intensive Care Med 1985;11:68-75
CrossRef | Web of Science | Medline
To the Editor:
The study by the Acute Respiratory Distress Syndrome Network was well conducted, with an adequate sample size. The researchers maintained plateau pressure at 45 to 50 cm of water in the group that received traditional tidal volumes. A consensus conference on mechanical ventilation recommended limiting end-inspiratory plateau pressure to 35 cm of water or less in patients with the acute respiratory distress syndrome.1
As the authors mention in their discussion, a greater difference in tidal volumes between the two groups in their trial may explain the difference in results between their study and previous studies.2-4 The greater difference in tidal volumes also suggests a greater difference in plateau pressures between the two groups. In the other studies, the mean (±SD) plateau pressures on days 5 through 7 in the groups that received traditional tidal volumes were 29±7 cm of water2 and 31±9 cm of water3; these values are considerably lower than the value on day 7 in this study (37±9 cm of water). Unconventionally high plateau pressures in the group treated with traditional tidal volumes may account for the different outcomes in this study and may make the results less applicable to clinical practice.
Did this study prove that low tidal volumes were beneficial or did it prove that unconventionally high plateau pressures were harmful? Even if low tidal volumes are beneficial and improve clinically important outcomes, this study could have overestimated the effects of low tidal volumes because of the unusually high tidal volumes and high plateau pressures used in the group treated with traditional tidal volumes.
4 ReferencesYuji Oba, M.D.
Gary A. Salzman, M.D.
University of Missouri–Kansas City, Kansas City, MO 64108-27921
Slutsky AS . Mechanical ventilation: American College of Chest Physicians' Consensus Conference. Chest 1993;104:1833-1859[Erratum, Chest 1994;106:656.]
CrossRef | Web of Science | Medline2
Stewart TE ,Meade MO ,Cook DJ , et al. Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. N Engl J Med 1998;338:355-361
Full Text | Web of Science | Medline3
Brochard L ,Roudot-Thoraval F ,Roupie E , et al. Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. Am J Respir Crit Care Med 1998;158:1831-1838
Web of Science | Medline4
Brower RG ,Shanholtz CB ,Fessler HE , et al. Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 1999;27:1492-1498
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We agree that positive end-expiratory pressure can confer lung protection by increasing lung recruitment. However, the higher positive end-expiratory pressure (and fraction of inspired oxygen) in the group treated with lower tidal volumes was necessary to achieve the same level of arterial oxygenation as that in the group treated with traditional tidal volumes. Moreover, respiratory-system compliance was lower in the group treated with lower tidal volumes. These observations suggest that there was less lung recruitment in this group. The buffering of acidosis in our trial was only one of several explanations offered to account for the difference between our results and those of previous trials.
Most patients who die with acute lung injury have dysfunction of multiple organs and systems. We do not have sufficient data to assess the role of cardiac output or organ microcirculation. The number of days without organ failure was higher and the plasma interleukin-6 concentration was lower in the group treated with lower tidal volumes, suggesting that lung protection reduced inflammation in nonpulmonary organs. The volume-assist–control mode was used in our trial to control tidal volume. In two studies involving patients with acute lung injury, gas exchange did not differ according to whether the pressure-controlled or volume-controlled mode was used.1,2
The recommendation of the American–European consensus conference to limit the plateau pressure to 35 cm of water or less or to 30 to 40 cm of water3 was based on experiments in animals that demonstrated acute lung injury from overdistention. Our trial was designed to assess the beneficial effects of reduced lung stretch as compared with the potential adverse effects of ventilation with lower tidal volumes in patients with acute lung injury. With the traditional-tidal-volume approach, there was no goal to maintain the plateau pressure at 45 to 50 cm of water. The primary goal was to maintain a traditional tidal volume of 12 ml per kilogram of predicted body weight (approximately 10 ml per kilogram of measured weight). The tidal volume was reduced if necessary to maintain the plateau pressure below a traditional limit (50 cm of water), as in the other recent trials. The mean plateau pressures in the group treated with traditional tidal volumes were 33 and 34 cm of water on days 1 and 3, respectively — values within the limits of the consensus recommendations. The mean plateau pressure of 37 cm of water on day 7, when most patients no longer required assistance with breathing, were being weaned from the ventilator, or had died, does not accurately represent the traditional protocol. Tidal volumes and mortality in the group treated with traditional tidal volumes were similar to those in similar groups in other trials.4,5 Our study proved that a strategy of using lower tidal volumes was better than the traditional-tidal-volume strategy.
5 ReferencesRoy G. Brower, M.D.
Johns Hopkins University, Baltimore, MD 21287Michael A. Matthay, M.D.
University of California, San Francisco, San Francisco, CA 94143Arthur Wheeler, M.D.
Vanderbilt University, Nashville, TN 372321
Mercat A ,Graini L ,Teboul J-L ,Lenique F ,Richard C . Cardiorespiratory effects of pressure-controlled ventilation with and without inverse ratio in the adult respiratory distress syndrome. Chest 1993;104:871-875
CrossRef | Web of Science | Medline2
Lessard MR ,Guerot E ,Lorino H ,Lemaire F ,Brochard L . Effects of pressure-controlled with different I:E ratios versus volume-controlled ventilation on respiratory mechanics, gas exchange, and hemodynamics in patients with adult respiratory distress syndrome. Anesthesiology 1994;80:983-991
CrossRef | Web of Science | Medline3
Artigas A ,Bernard GR ,Carlet J , et al. The American-European Consensus Conference on ARDS, part 2: ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Am J Respir Crit Care Med 1998;157:1332-1347
Web of Science | Medline4
Anzueto A ,Baughman RP ,Guntupalli KK , et al. Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. N Engl J Med 1996;334:1417-1421
Full Text | Web of Science | Medline5
Brochard L ,Roudot-Thoraval F ,Roupie E , et al. Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. Am J Respir Crit Care Med 1998;158:1831-1838
Web of Science | Medline
- Citing Articles (5)
Citing Articles
1
Alessandro Beda, Frederico C. Jandre, Antonio Giannella-Neto. (2010) A Numerical Model of the Respiratory Modulation of Pulmonary Shunt and PaO2 Oscillations for Acute Lung Injury. Annals of Biomedical Engineering 38:3, 993-1006
CrossRef2
Keisuke Tomii, Ryo Tachikawa, Kazuo Chin, Kimihiko Murase, Tomohiro Handa, Michiaki Mishima, Kyosuke Ishihara. (2010) Role of Non-invasive Ventilation in Managing Life-threatening Acute Exacerbation of Interstitial Pneumonia. Internal Medicine 49:14, 1341-1347
CrossRef3
Manuela Iglesias, Elisabeth Martinez, Joan Ramon Badia, Paolo Macchiarini. (2008) Extrapulmonary Ventilation for Unresponsive Severe Acute Respiratory Distress Syndrome After Pulmonary Resection. The Annals of Thoracic Surgery 85:1, 237-244
CrossRef4
John L. Moran, Andrew D. Bersten, Patricia J. Solomon. (2005) Meta-analysis of controlled trials of ventilator therapy in acute lung injury and acute respiratory distress syndrome: an alternative perspective. Intensive Care Medicine 31:2, 227-235
CrossRef5
John G. Laffey, Donall O’Croinin, Paul McLoughlin, Brian P. Kavanagh. (2004) Permissive hypercapnia — role in protective lung ventilatory strategies. Intensive Care Medicine 30:3, 347-356
CrossRef
