A young woman was admitted with respiratory failure requiring invasive ventilation. She had bilateral lobar consolidation and positive urinary pneumococcal antigen. She was ventilated with protective lung strategies but required FiO2 of between 0.8-1.0. A PEEP of 18 was set. She was ventilated for over 2 weeks, and was tracheostomised but was discharged from the ICU after 3 weeks.
How is PEEP utilised in the ventilatory strategies in the management of Adult Respiratory Distress Syndrome?
Acute respiratory distress syndrome (ARDS) is a diffuse, inflammatory lung injury leading to increased pulmonary vascular permeability, increased lung weight and loss of aerated tissue and was initially described in 1967 by Ashbaugh. The American-European Consensus Conference (AECC) defined it in 1994 as the acute onset of hypoxaemia (PaO2/FiO2 ratio ≤ 200mmHg) with bilateral infiltrates on chest radiograph and no evidence of left atrial hypertension. Issues have arisen with this definition since inception, which include difficulties in distinguishing hydrostatic oedema, poor reliability of chest radiograph interpretation and sensitivity of PaO2/FiO2 to different ventilator settings. In 2012 the ARDS task force developed the Berlin definition. This consensus process focused on improving feasibility, validity and reliability and was evaluated using a meta-analysis of 4457 patients with ARDS from 7 distinct data sets. It has 3 mutually exclusive severity categories.
Using the above data sets, mortality increased from 27% in mild ARDS, to 32% (moderate) and 45% in severe ARDS. Compared with the AECC definition, this has a better predictive validity for mortality with an area under the receiver-operating curve (AUROC) of 0.577 vs 0.536 (p<0.001), although both values are low(1).
Protective lung ventilation strategies in ARDS include using 6mls/kg tidal volumes and a plateau pressure of ≤ 30cmH2O. This was shown to decrease mortality (31% vs 29.8%, p=0.007) and increase ventilator-free days (12 vs 10, p=0.007) when compared to 12ml/kg predicted body weight in patients with ALI and ARDS. The mean plateau pressures were 25±6cm and 33±8cm of water (p=<0.001). They allowed plateau pressures of ≥ 50cm H2O in the bigger volume group; the low tidal volume group had higher FiO2s, PEEP levels, respiratory rates and pCO2s. This trial by the ARDSNet group in 2000 was stopped early due to the decreased mortality in the low volume group(2).
Positive end-expiratory pressure increases the proportion of aerated lung and therefore leads to improved arterial oxygenation and reduces the shearing forces that occur between aerated and non-aerated lung. Conversely, it may cause circulatory depression, pulmonary oedema and further lung injury from increased airway pressures and lung volumes. Below is the ARDSNet PEEP strategy.
In 1998 Amato et al compared conventional ventilation with a protective strategy, which was associated with improved survival at 28 days (p<0.001). The 53 patients were assigned to either a low PEEP, 12ml/kg tidal volume and normal pCO2 conventional strategy or protective strategy involving PEEP above the lower inflection point, 6ml/kg tidal volume, peak pressures of 20 cmH2O and permissive hypercapnia. The protective ventilation group had a 28-day survival benefit (p<0.001), although there was no difference in survival from hospital. The protective group also weaned from mechanical ventilation faster (p=0.005) and had less barotrauma. The study was stopped early due to the survival difference. Retrospective analysis found three significant prognostic factors: APACHE II score, mean PEEP and driving pressures (Pplat-PEEP) in first 36 hours. They believed that the benefit of high PEEP was more pronounced than that of Pplat, although the study was not designed to look specifically at PEEP(3).
Villar conducted a similar study comparing 9-11ml/kg tidal volume with PEEP of ≥5cmH2O (mean 9.0± 2.7 cmH2O) to 5-8ml/kg and a PEEP that equalled the inflection point + 2 cmH2O (mean 14.1± 2.8 cmH2O, p<0.001). It only included patients with established ARDS. This was stopped early as the protective group had significantly better mortality outcomes and ventilator-free days. Again this study was looking at tidal volumes combined with PEEP. In both studies, it is therefore difficult to ascribe the contribution to the mortality benefit made by higher PEEP values. Inflection points can be difficult to establish clinically and even in this study the investigators were unable to find the inflection point in 5 patients, in whom the PEEP was arbitrarily set at 15 cmH2O. After day 1, PEEP was not defined by a protocol and was at the clinician’s discretion.
In 2004, the ALVEOLI trial randomised 549 ALI/ARDS patients to either high PEEP (mean 13.2± 3.5cmH2O) or low PEEP (mean 8.3±3.2cmH2O) with 6ml/kg tidal volume and plateau pressure ≤ 30cmH2O. They found no difference in mortality rates (27.5% versus 24.9%, p=0.48) or ventilator-free days(5). Patients in the high PEEP group were older had higher APACHE III scores and lower PaO2/FiO2 ratios. PEEP was adjusted according to PEEP/FiO2 tables. This study was also stopped early on the grounds of futility in finding statistical differences.
An unblinded randomised controlled trial by Mercat in 2008 compared a minimum distension strategy of 5-9 cmH2O PEEP to a increased recruitment strategy where PEEP was set to reach a plateau pressure of 28-30 cmH2O (tidal volumes were 6ml/kg). There was no significant difference in mortality although the increased recruitment group significantly reduced the duration of mechanical ventilation and duration of organ failure (both p=0.04). It was associated with higher compliance, better oxygenation reduced use of rescue therapies and larger fluid requirements. The mean total PEEP values were 8.4(1.9) and 15.8(2.9) respectively on day one(6). It included ALI patients and the PaO2/FiO2 ratios of the two groups of patients were significantly different on day one, which may suggest slightly different patient groups.
A similar study by Meade et al compared average PEEP values of 14.6 to 9.8cmH2O (p<0.001) in 983 patients with set tidal volumes of 6ml/kg, albeit different plateau pressures (30 v 40cmH20). Mortality and barotrauma rates were not significantly different however the barotrauma recorded only included pneumothorax, pneumomediastinum etc. It found lower rates of hypoxaemia in the higher PEEP group(7).
Current Surviving Sepsis guidelines (2012) recommend PEEP should be applied to avoid atelectotrauma (grade 1B) and higher rather than lower PEEP levels for patients with sepsis-induced moderate to severe ARDS (grade 2B). They suggest either titrating PEEP according to thoraco-pulmonary compliance and thereby balancing lung recruitment and overdistension or to the severity of oxygenation deficit as guided by the FiO2(8).
Tidal volumes of 6mls/kg and limiting plateau pressures to ≤ 30cmH2O are well proven to improve survival in ARDs. However it is noted that the traditional ventilation strategy group in the ARDSnet study did use excessive volumes of 12ml/kg and allowed peak pressures up to 50 cmH2O.
There is no ‘one size fits all’ strategy for positive end expiratory pressure in ARDs, and in comparison to prescriptive tidal volume strategies, recommendations are not so explicit. Experienced investigators found it difficult sometimes to establish inflection points so this may be difficult to translate into clinical practice.
The perceived advantages of high PEEP must be balanced against the possible detrimental effects on the cardiovascular system. Higher PEEP does not appear to convey any survival advantage although has been shown to improve many secondary outcomes. It may be more advantageous in the moderate and severe ARDs groups. This is unclear from the above studies as all included mild ARDS/ALI.
1) The ARDS definition task force. The Berlin definition of acute respiratory distress syndrome. Journal of the American Medical Association 2012; 307(23): 2526-33
2) The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes from acute lung injury and the acute respiratory distress syndrome. New England Journal of Medicine 2000; 342(18): 1301-8
3) Amato MB, Barbas CS, Medeiros DM et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. New England Journal of Medicine 1998; 338(6): 347-54
4) Villar J, Kacmarek RM, Perez-Mendez L et al. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: A randomized, controlled trial. Critical Care Medicine 2006; 34(5): 1311-8
5) The National Heart, Lung and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. The ALVEOLI trial. New England Journal of Medicine 2004; 351(4): 327-36
6) Mercat A, Richard J-CM, Vielle B et al. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome. Journal of the American Medical Association 2008; 299(6): 646-55
7) Meade MO, Cook DJ, Guyatt GH et al. Ventilation strategy using low tidal volumes, recruitment manoeuvres, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome. Journal of the American Medical Association 2008; 299(6): 638-45
8) Dellinger RP, Levy MM, Rhodes A et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock 2012. Critical Care Medicine 2013; 41(2): 580-637