ARDS

Summary of papers not included for final recommendation

Randomised controlled studies

1. Effect of Mechanical Ventilation on Inflammatory Mediators in Patients With Acute Respiratory Distress Syndrome

A Randomized Controlled Trial

Peter M. Suter, Cosimo Tortorella, Renato De Tullio, Jean Michel Dayer, Antonio Brienza, Francesco Bruno, Arthur S. Slutsky.

JAMA. 1999;282:54-61

In a randomised controlled trial in the intensive care units of 2 European hospitals from November 1995 to February 1998 forty-four patients with acute respiratory distress syndrome were enrolled, 7 of whom were withdrawn due to adverse events. Patients were randomized to either the control group (n = 19): tidal volume to obtain normal values of arterial carbon dioxide tension (35-40 mmHg) and positive end-expiratory pressure (PEEP) producing the greatest improvement in arterial oxygen saturation without worsening hemodynamics; or the lung-protective strategy group (n = 18): tidal volume and PEEP based on the volume-pressure

curve.

Main outcome measures- Pulmonary and systemic concentrations of inflammatory mediators approximately 36 hours after randomization.

Conclusions- Mechanical ventilation can induce a cytokine response that may be attenuated by a strategy to minimize overdistention and recruitment/derecruitment of the lung. Whether these physiological improvements are associated with improvements in clinical end points should be determined in future studies.

6. Long-term effects of two different ventilatory modes on oxygenation in acute lung injury. Comparison of airway pressure release ventilation and volume-controlled inverse ratio ventilation."

Sydow M, Burchardi H, Ephraim E, Zielmann S and Crozier TA.

American Journal of Respiratory & Critical Care Medicine 1994; 149: 1550-6.

A total of 18 patients with acute lung injury (ALI) were sequentially ventilated with two different modes of mechanical ventilation, each applied for a period of 24 h: (1) volume-controlled inverse ratio ventilation (VC-IRV), (2) airway pressure release ventilation (APRV). The individual sequence of both ventilatory modes was randomized.

Conclusions:- The improvement was significantly different between both ventilatory modes (p < 0.01). We conclude that this indicates a progressive alveolar recruitment over time during ventilation with APRV

9. Prospective randomized trial comparing pressure-controlled ventilation and volume-controlled ventilation in ARDS.

Esteban A, Alia I, Gordo F, et al.

Chest 2000; 117: 1690-6.

Objectives: To compare in-hospital mortality of patients with ARDS ventilated with either pressure-controlled ventilation (PCV) or volume-controlled ventilation (VCV) with a square-wave inspiratory flow.

Design: Multicenter and randomized trial of seventy-nine patients having ARDS, as defined by the American-European Consensus Conference.

Interventions: Patients were randomly assigned to be ventilated with either PCV (n = 37) or VCV (n = 42). In both instances, inspiratory plateau pressure was limited to < or = 35 cmH2O.

Conclusions: The increased number of extrapulmonary organ failures developed in patients of the VCV group was strongly associated with a higher mortality rate. The development of organ failures was probably not related to the ventilatory mode.

13. Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure

Rappaport SH, Shipner R, Yoshihara G, et al.

Critical Care Medicine 1994; 22: 22-32.

Objectives: To assess the feasibility and utility of early and sustained use of pressure-limited ventilation in patients with this clinical syndrome.

Design: Randomized, prospective trial of 27 patients in medical intensive care unit (ICU) of a university hospital

Conclusions: Pressure-limited ventilation can be used safely and is well tolerated as an initial mode of ventilatory support in patients with acute hypoxic respiratory failure. Because the early initiation of pressure-limited ventilation is associated with lower peak airway pressure and more rapid improvement in static thoracic compliance than volume-controlled ventilation, pressure-limited ventilation may have a beneficial role when used as the primary ventilatory modality in patients with this clinical condition.

Not looking at primary area of study

2. The relation of pneumothorax and other air leaks to mortality in the acute respiratory distress syndrome

Weg, J. G. Anzueto, A. Balk, R. A. Wiedemann, H. P. Pattishall, E. N. Schork, M. Wagner, L. A.

New England Journal of Medicine 1998; 338: 341-346.

From a prospective trial of aerosolized synthetic surfactant in 725 patients with the acute respiratory distress syndrome induced by sepsis they compared the ventilatory pressures and volumes in the patients without any air leaks with the pressures and volumes in those with pneumothorax or with any air leaks RESULTS: There were no significant differences between patients with air leaks and those without air leaks in any pressure or volume examined. Conclusions:- In patients with sepsis-induced acute respiratory distress syndrome who were receiving mechanical ventilation with conventional pressures and volumes, there were no significant correlations between high ventilatory pressures or volumes and the development of pneumothorax or other air leaks.

7. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome."

Morris AH, Wallace CJ, Menlove RL, et al.

American Journal of Respiratory & Critical Care Medicine 1994; 149: 295-305.

The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria.

Outcome measure- Survival at 30 days after randomization.

Conclusions- There was no significant difference in survival between the mechanical ventilation and the extracorporeal CO2 removal groups. Both groups had low mortality when compared to historical controls. They do not recommend extracorporeal support as a therapy for ARDS. Extracorporeal support for ARDS should be restricted to controlled clinical trials.

Cohort studies

8. Comparison of volume control and pressure control ventilation: is flow waveform the difference?

Davis K, Jr., Branson RD, Campbell RS and Porembka DT

Journal of Trauma-Injury Infection & Critical Care 1996; 41: 808-14.

Objective: To examine the hypothesis that a decelerating inspiratory flow waveform is responsible for improvements in gas exchange during pressure control ventilation for acute lung injury.

Design: Prospective, controlled, crossover study of twenty-five patients with acute lung injury requiring mechanical ventilation

Conclusions: Both pressure control ventilation and volume control ventilation with a decelerating flow waveform provided better oxygenation at a lower peak inspiratory pressure and higher mean airway pressure compared to volume control ventilation with a square flow waveform. The results of our study suggest that the reported advantages of pressure control ventilation over volume control ventilation with a square flow waveform can be accomplished with volume control ventilation with a decelerating flow waveform

3. Cardiorespiratory effects of pressure-controlled ventilation with and without inverse ratio in the adult respiratory distress syndrome

Mercat, A. Graini, L. Teboul, J. L. Lenique, F. Richard, C.

Chest 1993: 104: 871.

A study to assess the cardiorespiratory effects of pressure-controlled ventilation and pressure-controlled inverse ratio ventilation , they compared pressure-controlled ventilation with an inspiratory-to-expiratory time ratio (I/E) of 1/2 (PCV) and of 2/1 (PC-IRV) to volume-controlled ventilation (VCV) with an I/E of 1/2 in 10 patients suffering from the adult respiratory distress syndrome. Each ventilatory mode was applied for 1 h in a randomized order.

Conclusions- Results suggest that neither PCV nor PC-IRV bring any benefit over VCV in terms of arterial oxygenation. Moreover, the increase in mPaw induced by PC-IRV may be deleterious to the CI and DO2.

4. 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

Lessard, M. R. Guerot, E. Lorino, H. Lemaire, F. Brochard, L.

Anesthesiology 1994; 80: 983.

Nine patients with moderate to severe ARDS had their lungs ventilated with VC, PCV with a conventional ratio and PCIRV. Ventilator settings were adjusted to keep tidal volume, respiratory rate, FiO2, and total-PEEP constant in every mode. With each mode, a complete set of ventilatory, hemodynamic, and gas exchange parameters was obtained after 30 min.

CONCLUSIONS: In this prospective controlled study, no short-term beneficial effect of PCV or PCIRV could be demonstrated over conventional VC with PEEP in patients with ARDS.

5. Inverse ratio ventilation in acute respiratory distress syndrome: a six-hour controlled study

Mercat, A. Titiriga, M. Anguel, N. Richard, C. Teboul, J. L.

American Journal of Respiratory & Critical Care Medicine 1997; 155:1837.

To assess the cardiorespiratory effects of a prolonged application of inverse ratio ventilation, thy compared IRV (I/E = 2) with conventional ventilation for 6 h each in a randomized order, with constant tidal volume (VT) and total positive end-expiratory pressure (PEEP(tot)) in eight patients with acute respiratory distress syndrome (ARDS).

Conclusions- That IRV at a ratio that results in a significant intrinsic PEEP does not improve Pa(O2), enhances CO2 elimination, decreases cardiac output (CO), and does not exert any time-dependent effect

10. Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study.

Hickling KG, Walsh J, Henderson S and Jackson R

Critical Care Medicine 1994; 22: 1568-78.

Objectives: To evaluate the outcome in patients with severe adult respiratory distress syndrome (ARDS) managed with limitation of peak inspiratory pressure to 30 to 40 cm H2O, low tidal volumes (4 to 7 mL/kg), spontaneous breathing using synchronized intermittent mandatory ventilation from the start of ventilation, and permissive hypercapnia

Design: Prospective, descriptive study of 53 patients with severe ARDS having a lung injury score of > or = 2.5.

Conclusions: Support the hypothesis that limitation of peak inspiratory pressure and reduction of regional lung overdistention by the use of low tidal volumes with permissive hypercapnia may reduce ventilator-induced lung injury and improve outcome in severe ARDS. However, the hypothesis requires testing in a randomized trial as acute hypercapnia could potentially have some adverse as well as beneficial effects.

11. Hemodynamic and ventilatory effects associated with increasing inverse inspiratory-expiratory ventilation

Gore DC

Journal of Trauma-Injury Infection & Critical Care 1998; 45: 268-72.

Objective- To assess for an optimal I:E ratio, hemodynamic, ventilatory, and oxygenation parameters were determined in eight adult trauma patients with acute respiratory distress syndrome supported with pressure-control ventilation.

Conclusions- Suggests effectiveness of increasing inspiratory time to improve oxygenation, yet to the detriment of ventilation. This suggests that within the parameter confines of this study, the preferential I:E ratio is a balance between oxygen demands and ventilatory requirements.

12. Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993.

Milberg JA. Davis DR. Steinberg KP. Hudson LD.

JAMA. 273(4):306-9, 1995 Jan 25.

Objective-To analyze temporal trends in acute respiratory distress syndrome (ARDS) fatality rates since 1983 at one institution.

Design- Cohort study of consecutive adult patients meeting ARDS criteria were identified

Outcome measures- Hospital mortality

Conclusions- In this large series, they observed a significant decrease in fatality rates occurring largely in patients younger than 60 years and in those with sepsis syndrome as their risk for ARDS. They were unable to determine the extent to which experimental therapies or other changes in treatment have contributed to the observed decline in the ARDS fatality rate. Institution-specific rates and temporal trends in ARDS fatality rates should be considered in clinical trials designed to prevent ARDS and the high mortality associated with this syndrome.

14. High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation.

Lewandowski K. Rossaint R. Pappert D. Gerlach H. Slama KJ. Weidemann H. Frey DJ. Hoffmann O. Keske U. Falke KJ.

Intensive Care Medicine. 1997; 23:819-35.

OBJECTIVE: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). DESIGN: Uncontrolled prospective trial.

Patients: 122 patients with ARDS, consecutively admitted to the ICU.

Interventions: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) groups received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. Conclusions: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved.

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