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ARDS (I)

Principal Investigator: Dr Brian Cuthbertson

Tidal volume limitation and PEEP in Acute Lung Injury and Acute Respiratory Distress Syndrome

Current State: Complete  (23.12.02; Up-dated 08.05)

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Tidal volume limitation and PEEP in Acute Lung Injury and Acute Respiratory Distress Syndrome

Brian H Cuthbertson on behalf of the SICS EBM group

Senior Lecturer in Anaesthesia & Intensive Care, Health Services Research Unit, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD

Correspondence: b.h.cuthbertson@abdn.ac.uk 

SICS EBMG web site January 2003. Updated August 2005.

Citation: EBM Reviews. Scottish Intensive Care Society EBM Group. Cuthbertson BC. Tidal volume limitation and PEEP in Acute Lung Injury and Acute Respiratory Distress Syndrome. 2005. 

Background: The outcome from ARDS has not significantly improved in 30 years. The hypothesis that limitation of peak ventilatory pressures and volumes will improve outcome has existed for some years. A moderate evidence base exists in this area with 6 well designed RCT’s looking at outcome. 

Objectives: To critically appraise the evidence for tidal volume, peak pressure limitation and PEEP in ALI and ARDS and make an evidence-based practice recommendation. 

Search strategy: ARDS with subheadings- therapy / drug therapy limited to prospective trials/ or randomised or double blind method; human; AIM journals. 

Selection criteria: One reviewer (BHC) selected studies for inclusion and two others (IG and CC) independently checked the selections. One reviewer assessed trial quality and independently extracted the data (BHC). One reviewer edited the final CAT for quality and accuracy (CC). 

Data collection and analysis: Six randomised controlled trials involving 1647 patients and 14 other studies involving 2086 patients were included. Of these 14 studies:- 4 small randomised studies (pressure control versus volume controlled ventilation); 8 non-randomised (cohort studies of tidal volume limitation in ARDS) and 2 studies (ECMO and surfactant studies) were not directed on primary question. There were sufficient data to enable conclusions to be drawn from the 6 randomised trials. These were critically appraised with CATmaker™ software. The 14 other studies offered lower levels of evidence and were not used in final recommendation.  

Main results: Brower et al [1] showed no difference between small and traditional tidal volumes in ARDS (RRR 0% CI - 46% to 46%) but failed to exclude bias and study stopped early. Stewart et al [2] showed no difference in outcome between tidal volume and peak pressure limitation and control ventilation in those “at-risk” for ARDS (RRR  -7% OR –45% to 31%) but controls differed little from treatment group. Brochard et al [3] showed no benefit from reduced tidal volume compared to conventional approach in ARDS (RRR –23% CI –70% to 24%) but controls differed little from treatment group. In two studies by Amato et al [4](both reported in Amato NEJM 1998) showed that “protective ventilation” (Tidal volume 6ml/kg and peak pressure < 40cmH2O) reduced 28 day mortality in severe (MLIS > 2.5) ARDS (RRR –87% CI –154 to –20%) but this study was unblinded and lacked intention-to-treat analysis. The ARDSnet [5] study of 861 patients randomised patients to either tidal volumes of 12 ml/kg with peak pressures of >50cmH2O or tidal volumes of 6ml/kg with peak pressures of < 30cmH2O and showed a RRR of 23% (CI 7 to 39%) in a large well designed study with high power and small risk of bias. This study represents the majority of patients randomised to ARDS ventilation studies and represents level 1+ evidence. A published meta-analysis of the first 5 papers suggests that differences between the management of the control groups in these studies combined with the changes in clinical practice with regard to tidal volume setting means there is no scientific basis for the use of low tidal volumes (6ml/kg) in ARDS until further evidence is provided to exclude a harmful effect of low tidal volume in this group [6]. This assertion has been hotly debated in the literature. A further study looking at the role of differing PEEP algorithms (“High or low PEEP”) showed no difference in outcome between a high PEEP algorithm and a low PEEP algorithm when combined with the ARDSnet ventilatory strategy (RRR –10% CI –40 – +19%, ns) [7].

Reviewers conclusions:

• Grade A recommendation – Reducing ventilatory tidal volumes in line with the ARDSnet algorithm in patients with ARDS is likely to be beneficial for all-comers with ARDS in Scotland (see appendix 1). Some concern remains about the potential for harm of low tidal volumes (6ml/kg) but the ARDSnet trial results remain the best available evidence to guide the ventilatory management of ARDS.

• Grade A recommendation- There is no difference in mortality between “high” and “low” PEEP strategies in ARDS and thus either strategy could be safely used in your patients. It seems reasonable practice to use the original ARDSnet PEEP strategy.

Citations with links to CATs:

1. Brower RG, et al. Prospective, randomized, controlled clinical trial comparing traditional vesus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 1999;27:1492-8 cat
2. Stewart TE 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;338:355-61 cat
3. Brochard L et al. Tidal volume reduction for prevention of ventilator-induced ling injury in acute respiratory distress syndrome. Am J Respir Crit Care Med. 1998;158:1831-8 cat
4. Amato MBP, et al. Effect of protective-ventilation strategy on mortality in the Acute Respiratory Distress Syndrome. N Engl J Med. 1998;338:347-54 cat
5. ARDSnet. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and acute respiratory distress syndrome. N Engl J Med 2000;342:1301-8 cat
6. Eichacker PQ, et al. Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med. 2002 Dec 1;166(11):1510-4. Link.
7. The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus Lower Positive End-Expiratory Pressures in Patients with Acute respiratory Distress Syndrome. N Eng J Med 2004;351;327-36. cat.
8. Other 14 studies - summary cat

Appendix 1:

Anon. Ventilation with lower tidal volumes as compared to traditional tidal volumes for acute lung injury and ARDS.  New England Journal of Medicine 2000; 342: 1301-1308.