Question 29

With respect to positive end-expiratory pressure (PEEP) in a ventilated patient with acute respiratory distress syndrome (ARDS):

a) Describe the possible approaches to setting PEEP. (80% marks)

b) List the disadvantages of excessive PEEP in this situation. (20% marks)

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College answer

•    PEEP setting adjusted to FiO2, increasing with increasing FiO2 according to the ARDSNet studies (low Vt study NEJM 2000, PEEP 5 – 20+ with FiO2 0.3 – 1.0 and ALVEOLI high PEEP study NEJM 2004 PEEP 5 – 24 with FiO2 0.3 – 1.0) or clinical assessment 
•    Use of lung mechanics to set PEEP – requires the static measurement of P-V curve e.g. using super-syringe. Patient sedated and paralysed and ventilated at FiO2 1.0 and zero PEEP with lung inflation in 50-100ml increments from FRC using a super-syringe followed by deflation in similar steps. Pressure and volume are recorded simultaneously and the P-V curve is constructed from the data. 
Typically requires identification of lower infection point on P-V curve (on VC mode) and setting of PEEP 2 cm H2O above the LIP. 
•    PEEP adjusted to maximise static compliance  
(C = Vt / (Pplateau – PEEP) 
•    Optimal (or best) PEEP – a level of PEEP that optimizes PaO2 and compliance without interfering with tissue oxygen delivery – ideally achieved during or immediately after recruitment manoeuvre, e.g. in Staircase Recruitment Manouevre best PEEP is 2.5 cmH2O above derecruitment point 
•    Transpulmonary pressures (TPP) to guide setting of PEEP – this requires real time measurement of oesophageal pressures (by placement of an oesophageal balloon) to keep the TPP (Paw-Pes) < 25 cm H2O at end inspiration and between 0 – 10 cm H2O at end expiration, while applying the low tidal volume ARDSNet ventilation strategy.  
b)      Disadvantages of excessive PEEP in patients with ARDS 
•    Overdistention of non-diseased alveoli resulting in further injury (VILI) 
•    Increased risk of barotrauma 
•    Increased dead space effect due to over-distension and also due to reduction in blood flow to alveoli • CO2 retention 
•    Reduced venous return to the heart, decreased cardiac output and a fall in blood pressure, vital organ perfusion. 
•    May decrease venous return from the abdomen, increasing renal/portal vein pressure and decreasing perfusion of kidneys/gut and increasing IAP 
•    Increased ICP 
•    May increase right to left shunt (increased pulmonary vascular resistance) 
Additional Examiners' Comments: 
Overall there was poor understanding of this topic and some candidates were unable to provide basic details. In the responses to part (a) there was generally good breadth in regard to the options of setting best PEEP, however there was often little depth in the options given. In part (b) most answers focused on the cardiorespiratory complications. There were very few candidates who mentioned increased intra-abdominal and intra-cranial pressures as potential complications. 




These issues undergo a thorough exploration in the chapter on how to determine the optimal PEEP for open lung ventilation in ARDS.

In brief:

  • Use an arbitrarily high PEEP: set to 15-20cmH2O.
    • Meta-analysis of LOVS, ALVEOLI and PROGRESS has suggested that severe ARDS patients (P/F ratio under 200) benefit from higher PEEP settings.
    • CT data suggests that in most ARDS patients the optimal PEEP is around 16cm H2O
  • Use the ARDSNet PEEP/FiO2 escalation tables (setting the PEEP according to the severity of the oxygenation failure)
    • The tables were used in the ARMA and LOVS trials, and are therefore associated with improved survival in ARDS
    • However, the main hypothesis of those trials was related more to tidal volumes and not to PEEP selection.
    • Recently, there has been a move away from oxygenation-based PEEP selection, and towards an "open lung" approach with PEEP being selected on the basis of ideal end-expiratory lung unit recruitment
  • Titrate PEEP according to maximum compliance, i.e. set the PEEP which achieves the highest static compliance
    • This has the advantage of being tailored to each specific patient
    • The physiological basis is sound (maximum compliance should occur when maximum recruitment but minimal overdistension has occurred).
    • No strong literature evidence exists
  • Set the PEEP using the lower inflection point of the pressure volume curve
    • On the pressure volume curve, the lower inflection point indicates the pressure at which alveolar recruitment is maximal (i.e. fewest alveoli are collapsed).
    • It is unclear where this point is on any given real-life curve
    • It is unclear whether we should use the lower (inspiratory) inflection point or the upper (expiratory) inflection point, and there are good theoretical arguments for each.
    • The measurement requires paralysis and - ideally - serial static measurements
  • Use a staircase recruitment (or derecruitment) manoeuvre to find the lowest PEEP at which the maximal oxygenation is maintained.
    • This has the advantage of having a very pragmatic endpoint, SpO2.
    • One recruits the lung, and then decreases PEEP incrementally until SpO2 begins to drop
    • The minimum PEEP which maintains the highest SpO2 is then selected as the "ideal" PEEP
    • The problem is, this PEEP may still expose some of the lung regions to cyclic atelectasis, and will not prevent biotrauma. As long as oxygenation is preserved, those lung regions will be ignored by this technique.
  • Using a PA catheter, titrate PEEP to achieve the smallest intrapulmonary shunt
    • Shunt will increase with atelectasis or derecruitment
    • Shunt will also increase with overdistension
    • Monitoring the intrapulmonary shunt is possible only by using a PA catheter
    • These days this technique is at least as unpopular as the PA catheter
  • Titrate PEEP according to the transpulmonary pressure
    • Oesophageal pressure (Pes) derived from an oesophageal balloon manometer is a satisfactory surrogate for pleural pressure.
    • Transpulmonary pressure = (Pplat - Pes)
    • This variable ca be used to titrate PEEP as well as tidal volume, as it relates to derecruitment and overdistension.
    • The ideal TPP is 0-10 in end-expiration and no more than 25 in inspiration
  • Using electrical impedance tomography, titrate PEEP to achieve the highest electrical impedance in the thorax (i.e. the greatest amount of aerated lung)
    • This is promising bu still largely experimental
    • No hard outcomes adata is available, only animal and "feasibility" studies.
  • Sequential CT scans to visually determine a PEEP at which the greatest volume of lung is recruited during end-expiration
    • CT volumetric measurements are the gold standard of recruitment research
    • The disadvantages are related to safety and logistics, i.e. transport to and from the CT scanner as well as radiation exposure.


Disadvantages of excessive PEEP are discussed in the chapter on ventilator-associated lung injury, as excessive pressure at end-expiration is pathologically indistinguishable from excessive pressure at inspiration, except in terms of magnitude. The short statement about each issue borows heavily from the college answer to  Question 10 from the first paper of 2012 . In summary, the problems are:

  • Volutrauma
    • Over-distension of normal alveolar units to trans pulmonary pressures above ~30 cm H2O
      causes basement membrane stretch and stress on intracellular junctions.
  • Barotrauma
    • Increasing the trans-pulmonary pressures above 50 cm H2O will cause disruption of the basement membranes
  • Biotrauma
    • Mechanotransduction and tissue disruption leads to upregulation and release of chemokines and  cytokines with subsequent WBC attraction and activation resulting in pulmonary and systemic inflammatory response and multi-organ dysfunction.
  • Cardiovascular effects
    • Excessive PEEP results in increased pulmonary pressure, increased right ventricular afterload and decreased cardiac preload.
    • Right heart failure may lead to haemodynamic instability.
  • Extrathoracic effects
    • Excessive PEEP decreases cardiac output by decreasing preload, and increases central venous pressure
    • The net result is decreased organ perfusion pressure, and therefore poorer organ function (including renal hepatic and splanchnic)


Gattinoni, Luciano, Eleonora Carlesso, and Massimo Cressoni. "Selecting the ‘right’positive end-expiratory pressure level." Current opinion in critical care 21.1 (2015): 50-57.

Grasso, Salvatore, et al. "ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end-expiratory pressure." American journal of respiratory and critical care medicine 176.8 (2007): 761-767.

Suter, Peter M., H. Barrie Fairley, and Michael D. Isenberg. "Optimum end-expiratory airway pressure in patients with acute pulmonary failure." New England Journal of Medicine 292.6 (1975): 284-289.

Pintado, María-Consuelo, et al. "Individualized PEEP setting in subjects with ARDS: a randomized controlled pilot study." Respiratory care 58.9 (2013): 1416-1423.

Chiumello, Davide, and Matteo Brioni. "Severe hypoxemia: which strategy to choose." Critical Care 20.1 (2016): 1.