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(Chest. 2001;120:1622-1627.)
© 2001 American College of Chest Physicians

Clinicians’ Approaches to Mechanical Ventilation in Acute Lung Injury and ARDS*

B. Taylor Thompson, MD; Doug Hayden, MA; Michael A. Matthay, MD, FCCP; Roy Brower, MD and Polly E. Parsons, MD

* From the Pulmonary and Critical Care Unit, Department of Medicine (Dr. Thompson), Department of Biostatistics (Mr. Hayden), Massachusetts General Hospital and Harvard Medical School, Boston, MA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, the Department of Anesthesia, and the Cardiovascular Research Institute (Dr. Matthay), University of California, San Francisco, San Francisco, CA; Division of Pulmonary and Critical Care Medicine (Dr. Brower), Johns Hopkins University, Baltimore, MD; and Pulmonary and Critical Care Unit (Dr. Parsons), Fletcher Allen Health Care, Burlington, VT.

Correspondence to: B. Taylor Thompson, MD, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114; e-mail: tthompson1{at}partners.org


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: To examine clinicians’ approaches to mechanical ventilation in patients with acute lung injury (ALI; PaO2/fraction of inspired oxygen [FIO2] <= 300) and compare ventilator settings in patients with ARDS (PaO2/FIO2 <= 200) to settings in patients with milder oxygenation impairment (PaO2/FIO2 of 201 to 300).

Design: Retrospective analysis of baseline data from prospective randomized trials conducted by the National Institutes of Health ARDS Network between 1996 and 1999.

Setting: Ten clinical centers comprising 24 hospitals and 74 medical and surgical ICUs of the ARDS Network.

Measurements and results: The most common mode of mechanical ventilation in both groups was volume-assist control (56%). Synchronized intermittent mandatory ventilation (SIMV) or SIMV with pressure support was used more often in patients with PaO2/FIO2 of 201 to 300 than in patients with ARDS. The use of pressure-control ventilation was uncommon (10% overall), as was the use of permissive hypercapnia (6% of patients with ARDS and 3% of patients with PaO2/FIO2 of 201 to 300). The mean ± SD tidal volume was 10.3 ± 2 mL/kg of predicted body weight or 8.6 ± 2 mL/kg of measured weight for patients with ARDS, and was not significantly different for patients with PaO2/FIO2 of 201 to 300. Plateau pressures (Pplats) were lower in the PaO2/FIO2 of 201 to 300 group (27 ± 7 vs 31 ± 8 for the ARDS group; p = 0.0003) and were > 35 cm H2O in 26% of patients. Seventy-eight percent of patients with ARDS received <= 10 cm H2O of positive end-expiratory pressure.

Conclusions: Physicians in ARDS Network centers caring for patients early in the course of ALI/ARDS used volume-targeted ventilation and selected tidal volumes that resulted in Pplats generally < 35 cm H2O. The average tidal volume was similar for patients with ARDS vs those with milder oxygenation deficits.

Key Words: acute lung injury • ARDS • mechanical ventilation


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The best approach to mechanical ventilation for patients with acute lung injury (ALI) or ARDS has been controversial. Consensus conference conclusions1 2 recommended limitation of tidal volume and end-inspiratory airway pressures and acceptance of permissive hypercapnia. A survey3 of critical-care practitioners, conducted before this consensus statement and also before the publication of several clinical trials4 5 6 of low tidal volume ventilation, showed a preference for the assist-control mode. There was a wide range of preferred tidal volumes: 48% reported using volumes in the 10- to 15-mL/kg range and 45% reported using 5 to 9 mL/kg. Nearly all responded that airway pressure influenced their choice of tidal volume. There was also great disparity in how clinicians used supplemental oxygen and positive end-expiratory pressure (PEEP).3

The purpose of this study is to examine recent ventilator practices of clinicians caring for patients with ALI and ARDS. We reviewed ventilator settings of ALI/ARDS patients before enrollment in clinical trials conducted by the National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Baseline data from 902 patients participating in ARDS Network multicenter randomized trials between March 18, 1996, and May 28, 1999, were examined. The first 861 subjects participated in a randomized trial4 of lower tidal volume vs traditional tidal volume ventilation (6 mL/kg vs 12 mL/kg of predicted body weight [PBW]). The first 234 of these 861 patients were also enrolled in a clinical trial7 comparing ketoconazole vs placebo using a factorial design. The last 194 of the 861 subjects participated in a trial of lisofylline vs placebo, also in a factorial design (Edward Abraham, MD; personal communication; March 2001). Following the early stopping of the ventilator trial4 for efficacy, an additional 41 patients received lisofylline or placebo with 6-mL/kg PBW tidal volume.

Patients were eligible if they required mechanical ventilation for the acute onset of PaO2/fraction of inspired oxygen (FIO2) <= 300 (altitude adjustment in Denver and Salt Lake City), bilateral pulmonary infiltrates consistent with pulmonary edema, and no clinical evidence of left atrial hypertension. If measured, the pulmonary capillary wedge pressure was required to be <= 18 mm Hg.

Exclusion criteria included > 36 h elapsed since the above-mentioned inclusion criteria were met, age < 18 years, participation in other ALI/ARDS trials within 30 days, pregnancy, increased intracranial pressure, neuromuscular disease that could impair spontaneous breathing, sickle-cell disease, severe chronic respiratory disease, massive obesity, > 30% body surface area burns, comorbid conditions with estimated 6-month mortality > 50%, bone marrow or lung transplant, chronic liver disease (Child-Pugh class C), or attending physician refusal or unwillingness to commit full life support. Values closest to the time of initial protocol-specified ventilator change were chosen. Tidal volume was corrected for volume lost from gas compression and ventilator tubing compliance and expressed per kilogram of PBW as previously described.4

Mean values ( ± SD) for patients with ARDS vs patients with PaO2/FIO2 of 201 to 300 were compared with Student’s t test for continuous variables and a {chi}2 test for dichotomous variables. Linear and logistic regression were used to test the association of selected variables and covariates. Two-sided p values of < 0.05 were accepted as indicating statistical significance. All analyses were conducted with SAS version 6.12 (SAS Institute; Cary, NC).


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The participating centers of the ARDS Network have been outlined in previous publications.4 7 The network comprises 10 sites, 24 hospitals, and > 70 ICUs. During the approximately 3-year period of this study, 7,456 patients with ALI were identified in ARDS Network ICUs and 902 of those patients were enrolled in ARDS Network trials. Baseline characteristics of the subset of patients enrolled in the trial of lower vs traditional tidal volume (n = 861) have been reported elsewhere.4

Data on baseline ventilator settings (used in the 4-h interval prior to the initial protocol-specified ventilator changes) and arterial blood gas values indicating a PaO2/FIO2 <= 300 were available in 814 of the 902 patients and comprise the basis of this report (88 patients excluded). Modes of ventilation at baseline for patients with ALI, those with ARDS (PaO2/FIO2 <= 200), and those at the milder end of the ALI spectrum (PaO2/FIO2 of 201 to 300) are shown in Table 1 . The most common mode of mechanical ventilation used in all groups was volume-assist control (56%). Synchronized intermittent mandatory ventilation (SIMV) or SIMV plus pressure support was used more often in patients with PaO2/FIO2 of 201 to 300 than in patients with PaO2/FIO2 <= 200. The use of the pressure-control mode was uncommon (10% overall) and almost entirely confined to patients with ARDS (77 of 84 patients). The proportion of patients receiving volume-assist control was similar (61%) for those excluded from the study.


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  		Table 1.. Modes of Ventilation at Study Entry*

 
Ventilator settings, airway pressures, and arterial blood gas values for patients who received volume-targeted ventilation are shown in Table 2 . For this analysis, we defined volume-targeted ventilation as volume-assist control or SIMV and included patients receiving SIMV plus pressure support. There were no differences in tidal volume, but PEEP, FIO2, and set rate were lower in patients with PaO2/FIO2 of 201 to 300 vs those with ARDS. Plateau pressures (Pplats; measured after a 0.5-s inspiratory pause), but not peak or mean airway pressures, were higher in patients with PaO2/FIO2 <= 200.


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  		Table 2.. Ventilator Settings, Airway Pressure, and Arterial Blood Gas Values for Volume-Targeted Ventilation*

 
The mean tidal volume selected for the early management of ARDS was 10.3 mL/kg PBW. This was not significantly different from the mean tidal volume of 10.4 mL/kg PBW selected for patients with PaO2/FIO2 of 201 to 300 (Table 2) . When expressed per kilogram of actual (measured) weight, the tidal volumes were 9.0 ± 2.2 mL/kg and 9.1 ± 2.2 mL/kg for ARDS and PaO2/FIO2 of 201 to 300, respectively (p = 0.65). To further examine if the selection of initial tidal volume was influenced by the severity of oxygenation failure as manifest by a low PaO2/FIO2, we performed linear regression analysis on tidal volume vs the entire spectrum of PaO2/FIO2. There was no significant correlation between tidal volume and PaO2/FIO2 (p = 0.596). Tidal volume was similar (10.2 ± 1.9 mL/kg) in those excluded from the primary analysis.

Table 3 shows ventilator settings, airway pressures, and arterial blood gas values for patients whose baseline ventilator mode was pressure targeted rather than volume targeted. Pressure-targeted ventilation was defined as pressure control or pressure support as the sole mode of mechanical ventilation. There were no significant differences in the levels of pressure control, pressure support, or total respiratory rate between patients with ARDS vs those with PaO2/FIO2 of 201 to 300. Patients with PaO2/FIO2 of 201 to 300 received lower levels of PEEP. Only 10 patients received pressure-controlled inverse-ratio ventilation (PCIRV).


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  		Table 3.. Ventilator Settings, Airway Pressures, and Arterial Blood Gas Values for Pressure-Targeted Ventilation*

 
For both volume-targeted and pressure-targeted ventilation, mean PaO2 values were > 100 mm Hg for patients with PaO2/FIO2 of 201 to 300, suggesting the FIO2 and/or PEEP settings were generous (Tables 2 , 3) . Hypercapnia, defined as a PaCO2 >= 50 mm Hg, occurred in 6% of patients with ARDS and 3% of patents with PaO2/FIO2 of 201 to 300.

The levels of PEEP used for the entire ALI cohort ranged from 2 to 28 cm H2O, and 16 patients (14 patients with ARDS) were treated with zero end-expiratory pressure. Seventy-eight percent of patients with ARDS received <= 10 cm H2O, and 97% received <= 15 cm H2O PEEP. For patients with PaO2/FIO2 of 201 to 300, 88% received <= 10 cm H2O and 98% received <= 15 cm H2O PEEP. Figure 1 shows the mean PEEP levels used over a range of FIO2 values from 0.3 to 1.0 for all patients. Higher levels of PEEP correlated with higher inspired oxygen levels (p < 0.0001).



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  		Figure 1.. Baseline levels of PEEP for each FIO2.

 
To determine if ventilator preferences changed during the study, perhaps due to either the ongoing ARDS Network ventilator trial itself (which used volume assist-control mode to compare tidal volumes of 6 mL/kg PBW vs 12 mL/kg PBW) or external events (such as the publication of three trials, two with negative findings and one with positive findings, of lung protective ventilation), we tested for a linear trend in baseline tidal volume and the log odds of the proportion of patients receiving volume-assist control over time.5 6 8 The relationships of baseline tidal volume vs time (p = 0.177) or the proportion receiving volume-assist control (p = 0.348) over the 3-year period of the study were not significant. However, when the 41 patients enrolled in the lisofylline trial after the ARDS Network ventilator trial stopped (for efficacy in the low tidal volume group) were analyzed separately, clinician-selected tidal volumes were significantly lower (9.1 ± 2.2 mL/kg PBW vs 10.4 ± 1.8 mL/kg PBW for those enrolled before study termination; p = 0.0016). This suggests a change in practice in response to the study at ARDS Network hospitals.


   Discussion
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
For the early management of patients with ALI or ARDS in ARDS Network centers, volume-assist control was the most commonly selected mode of ventilation (56% overall) and volume-targeted ventilation was used in most patients (82%). For patients with milder oxygenation deficits (PaO2/FIO2 of 201 to 300), SIMV and SIMV plus pressure support were used with greater frequency than in patients with ARDS. Pressure-control use was uncommon, as was the use of > 10 cm H2O PEEP.

These findings are consistent with a survey3 of critical-care practitioners’ preferences obtained in late 1992 and published in 1996. The most favored modes of mechanical ventilation for patients with ARDS were volume-assist control (approximately 65%) and intermittent mandatory ventilation (approximately 20%). In the ARDS network studies, baseline tidal volumes in patients with volume-targeted ventilation were 10.3 ± 2 mL/kg PBW, or approximately 9 mL/kg of measured weight, which was within the range of tidal volumes most commonly preferred by survey respondents.3

The mean Pplat of 31 ± 8 cm H2O in patients with ARDS in this study was consistent with the consensus conference recommendations1 to limit end-inspiratory pressure to < 35 cm H2O. However, in 28% of patients receiving volume-targeted ventilation, Pplat exceeded this limit prior to enrollment in the ARDS Network trials.

Baseline tidal volumes used before enrollment in the ARDS Network trials are compared to tidal volumes used by clinicians and investigators in several studies conducted from 1989 to 1999 (Table 4 ). In the multicenter, international trial of aerosolized surfactant in ARDS (A. Anzueto, MD; personal communication; March 2000),9 the mean tidal volume on the day of study enrollment was 11.4 mL/kg of measured body weight, which is equivalent to approximately 13.7 mL/kg PBW. In the seven-center trial of ibuprofen in sepsis (G. Bernard, MD; personal communication; March 2000),10 the mean tidal volume among intubated patients with ALI on the day of enrollment was 10.3 mL/kg of measured body weight, equivalent to approximately 12.4 mL/kg PBW. These tidal volumes were prescribed by clinicians working in ICUs that were not participating in trials of pressure-limited and volume-limited mechanical ventilation strategies. Hence, these tidal volumes likely represent the standard practice for initial ventilator management of patients with ALI/ARDS during the time these studies were conducted (from 1989 to 1995).


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  		Table 4.. Clinician- and Investigator-Selected Tidal Volume in the 1990s*

 
Later in the 1990s, physician-prescribed tidal volumes used for early management of ALI/ARDS patients appear to be lower. The tidal volumes used in 1996 to 1999 prior to enrollment in the ARDS Network studies (10.3 mL/kg PBW)4 and the physician-prescribed tidal volumes used in the international survey of mechanical ventilation practices between 1996 and 1997 (10.5 mL/kg PBW)11 are approximately 2 to 3 mL/kg of PBW lower than the tidal volumes used earlier in the decade (Table 4) . The recent modest reduction in clinician-prescribed tidal volumes may have resulted from heightened physicians’ concerns for ventilation-associated lung injury.

The tidal volumes used by investigators in the traditional arm of the ARDS Network study, the control group of the pressure-limited and volume-limited study by Stewart et al,5 and in the "conventional" arm used by Brochard et al6 were, on average, intermediate between the tidal volumes selected by clinicians caring for patients earlier vs later in the 1990s (Table 4) .4 11 Thus, investigators designing trials of lower tidal volume ventilation in the mid-1990s appear to have selected "control" tidal volumes representative of an evolving practice toward the use of lower tidal volumes during this decade.

While there may have been a modest reduction of tidal volumes over the past decade, it is important to note that the tidal volume used in the ARDS Network ventilation management strategy that was ultimately found to be associated with improved outcome is substantially smaller yet. That strategy targeted a tidal volume of 6 mL/kg PBW (approximately 5 mL/kg of measured weight) that was further reduced, if needed, to a minimum of 4 mL/kg PBW to maintain a Pplat < 30 cm H2O.4 Additional studies will be needed to see if the results of the ARDS Network trial will accelerate the use of these much lower tidal volumes for the management of patients with ALI/ARDS.

In 1994, an American-European Consensus Conference on ALI and ARDS recommended a definition for ARDS that incorporated a PaO2/FIO2 threshold <= 200. The recommended definition of ALI was the same as for ARDS, except for a PaO2/FIO2 threshold <= 300.2 ALI thus refers to all patients with a PaO2 <= 300, including the subset with ARDS. Studies12 13 have suggested that the clinical characteristics, risk factors for lung injury, and outcomes are similar for patients with ALI vs the subset of patients with ARDS.

We anticipated that ventilator support would differ in patients across the spectrum of ALI, with low tidal volume ventilation or pressure-targeted ventilation used more commonly in patients with more severe oxygenation deficits. There were modest differences in modes of ventilation used for patients with ARDS vs those with PaO2/FIO2 of 201 to 300, with slightly more use of SIMV and less use of pressure control for the PaO2/FIO2 of 201 to 300 group. However, volume-targeted ventilation was used in a large majority of both the ARDS and PaO2/FIO2 of 201 to 300 groups, and pressure-control ventilation, especially PCIRV, was infrequently used.

Optimal use of PEEP and supplemental oxygen is also controversial.14 Most intensivists adjust PEEP and FIO2 to achieve an arterial oxygenation goal. In this study, physicians used, on average, 8.8-cm H2O PEEP and an FIO2 of 0.67 early in the course of patients with ARDS to achieve an average PaO2 of 78 mm Hg. Two studies8 15 of lung-protective ventilatory strategies incorporating higher PEEP levels (set on the basis of pressure-volume curves) have demonstrated reduced mortality or diminished lung and systemic cytokine release. The mean levels of PEEP on the first day of these two trials were 16.3 ± 0.7 cm H2O and 14.7 ± 2.7 cm H2O in the lung-protective groups. PEEP levels in the control groups were set to meet oxygenation goals and were 6 to 7 cm H2O. The levels of PEEP reported in the present study are similar to those in these control groups, and only 3% of patients with ARDS received >= 15 cm H2O of PEEP. These findings suggest that a traditional approach was used to set PEEP in the patients described herein.

There are some limitations to this study. First, the ventilator approaches reported in Tables 1 2 3 represent ventilator settings clinicians prescribed only during the first 36 h after onset of ALI or ARDS. We do not know if these approaches would have been maintained in the subsequent clinical courses. It is possible that tidal volumes would have been reduced or PEEP levels increased in some patients to limit inspiratory airway pressures or FIO2, respectively. Second, it is possible that the ventilator approaches used in the initial phase of ALI were influenced by clinicians’ familiarity with the ongoing ARDS Network trials, which used volume-assist control mode in all patients before weaning.4 Moreover, clinicians may have prescribed lower tidal volumes before their patients’ enrollments because the ARDS Network trial increased their concerns for overdistention or stretch-induced lung injury. The reduction in tidal volumes following completion of the ventilator trial suggests that clinicians practicing in ARDS Network hospitals were aware of and probably influenced by the study. Third, we do not have clinician-prescribed ventilator settings for patients excluded from the ARDS Network trial. These patients represent 88% of all patients with ALI identified in the network ICUs.

In summary, physicians caring for patients early in the course of ALI in ARDS Network hospitals favored volume-targeted ventilation and selected tidal volumes that resulted in Pplats generally < 35 cm H2O, in accordance with consensus recommendations. SIMV with or without pressure support was used more often in the PaO2/FIO2 of 201 to 300 group vs the ARDS subset, while pressure control, especially PCIRV, was uncommonly used. The average tidal volume (8.6 mL/kg of measured weight or 10.3 mL/kg PBW) was similar across the spectrum of PaO2/FIO2, was similar to the tidal volumes reported in a recent international survey, but was lower than tidal volumes used earlier in the 1990s. It remains to be seen if the results of recent clinical trials will accelerate the apparent evolution of practice toward using lower tidal volume ventilation for the management of ALI.


   Footnotes
 
Abbreviations: ALI = acute lung injury; FIO2 = fraction of inspired oxygen; PBW = predicted body weight; PCIRV = pressure-controlled inverse-ratio ventilation; PEEP = positive end-expiratory pressure; Pplat = plateau pressure; SIMV = synchronized intermittent mandatory ventilation

Supported by contracts NO1-HR 46054–64 from the National, Heart, Lung, and Blood Institute.

Received for publication January 22, 2001. Accepted for publication April 11, 2001.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. . ACCP Consensus Conference. (1993) Mechanical ventilation. Chest 104,1833-1859[Free Full Text]
  2. Bernard, GR, Artigas, A, Brigham, K, et al (1994) The American-European Consensus Conference on ARDS. Am J Respir Crit Care Med 149,818-824[Abstract]
  3. Carmichael, L, Dorinsky, P, Higgins, S, et al (1996) Diagnosis and therapy of acute respiratory distress syndrome in adults: an international survey. J Crit Care 11,9-18[CrossRef][ISI][Medline]
  4. . The Acute Respiratory Distress Syndrome Network. (2000) Ventilation with lower tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342,1301-1308[Abstract/Free Full Text]
  5. Stewart, TE, Meade, M, Cook, D, et al (1998) Evaluation of a ventilation strategy to prevent barotrauma in patients a high risk for acute respiratory distress syndrome. N Engl J Med 338,355-361[Abstract/Free Full Text]
  6. Brochard, L, Roudot-Thorval, F, Roupie, E, et al (1998) Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. Am J Respir Crit Care Med 158,1831-1838[Abstract/Free Full Text]
  7. . The ARDS Network. (2000) Ketoconazole for the early treatment of acute lung injury and acute respiratory distress syndrome. JAMA 283,1995-2002[Abstract/Free Full Text]
  8. Amato, MBP, Barbas, CSV, Medeiros, DM, et al (1998) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338,347-354[Abstract/Free Full Text]
  9. Anzueto, A, Baughman, R, Guntupalli, KK, et al (1996) Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. N Engl J Med 334,1419-1421
  10. Bernard, G, Wheeler, AP, Russel, JA, et al (1997) The effects of ibuprofen on the physiology and survival of patients with sepsis: the Ibuprofen in Sepsis Study Group. N Engl J Med 336,912-918[Abstract/Free Full Text]
  11. Esteban, A, Anzueto, A, Alia, I, et al (2000) How is mechanical ventilation employed in the intensive care unit? Am J Respir Crit Care Med 161,1450-1458[Abstract/Free Full Text]
  12. Doyle, RL, Szaflarski, N, Modin, GW, et al (1995) Identification of patients with acute lung injury: predictors of mortality. Am J Respir Crit Care Med 152,1818-1824[Abstract]
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  15. Raniere, VM, Suter, SP, Tortorella, C, et al (1999) Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 282,54-61[Abstract/Free Full Text]



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Arterial O2 Saturation versus O2 Extraction Ratio during Permissive Hypercapnia of ARDS Patients
Mohamad Abdelsalam Abdelkader
Chest Online, 23 Apr 2004 [Full text]
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