Show Summary Details
Page of

Respiratory support with positive end-expiratory pressure 

Respiratory support with positive end-expiratory pressure
Chapter:
Respiratory support with positive end-expiratory pressure
Author(s):

Ignacio Martin-Loeches

and Antonio Artigas

DOI:
10.1093/med/9780199600830.003.0094
Page of

PRINTED FROM OXFORD MEDICINE ONLINE (www.oxfordmedicine.com). © Oxford University Press, 2020. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy and Legal Notice).

date: 29 November 2020

Key points

  • Positive end-expiratory pressure (PEEP) is usually one of the first ventilator settings chosen when mechanical ventilation (MV) is initiated.

  • A sufficient level of PEEP is necessary to prevent alveolar derecruitment, without developing alveolar overdistension, dead space ventilation, and hypotension.

  • The ideal level of PEEP is that which prevents derecruitment of the majority of alveoli, while causing minimal overdistension.

  • The level of PEEP should be individualized and higher PEEP might be used in the more severe end of the spectrum of patients (acute respiratory distress syndrome) with improved survival.

  • A survival benefit for higher levels of PEEP has not been yet reported for any patient under MV but a higher PaO2/FiO2 ratio seems to be better in the higher PEEP group.

Introduction

Positive end-expiratory pressure (PEEP) is the pressure present in the airway (alveolar pressure) above atmospheric pressure that exists at the end of expiration. The term PEEP is defined in two particular settings. Extrinsic PEEP (PEEP applied by a ventilator) and intrinsic PEEP (PEEP caused by a non-complete exhalation that causes progressive air trapping). Applied (Extrinsic) PEEP—is usually one of the first ventilator settings chosen when mechanical ventilation (MV) is initiated. The application of PEEP has two primary purposes:

  • To increase lung volume in patients who have acute lung restriction in order to improve arterial oxygenation by recruiting or stabilizing alveolar units, and to protect the alveoli against injury during phasic opening and closing of atelectatic units that produces hypoxaemia;

  • To reduce the effort required for patients to trigger the ventilator or breathe spontaneously in the presence of dynamic hyperinflation and auto-PEEP.

It is important to consider that lung recruitment occurs during inspiration and PEEP is applied during expiration in order to maintain the alveolar units opened.

Physiological effects of PEEP

Applying PEEP increases alveolar pressure and alveolar volume. The increased lung volume increases the surface area by reopening and stabilizing collapsed or unstable alveoli. PEEP therapy can be effective when used in patients with a diffuse lung disease with a decrease in functional residual capacity (FRC). FRC is determined by primarily the elastic characteristics of the lung and chest wall, and in pulmonary diseases, such as ARDS, reduced because of the collapse of the unstable alveoli. Opening the alveoli with positive pressure improves the ventilation–perfusion match. After the shunt effect is modified to a ventilation–perfusion mismatch with PEEP (unoxygenated blood returning to the left side of the heart), lowered concentrations of oxygen can be used to maintain an adequate PaO2. PEEP therapy may also be effective in improving lung compliance [1]‌.

Lung protection ventilation is an established strategy of management to reduce and avoid ventilator induced lung injury and mortality. Levels of PEEP have been traditionally used from 5 to 12 cmH2O; however, higher levels of PEEP have also been proposed and updated in order to keep alveoli open, without the cyclical opening and closing of lung units (atelectrauma). Several studies have evaluated the effect of modest versus high levels of PEEP in patients with and acute respiratory distress syndrome (ARDS) [2]‌. A survival benefit for higher levels of PEEP has not been yet reported for any patient under MV, but a higher PaO2/FiO2 ratio seems to be better in the higher PEEP group. In addition, higher levels of PEEP have been associated with improved survival (about 10%) among the subgroup of patients with ARDS.

How to set the PEEP

The ideal level of PEEP is often difficult to set but in general is that which the majority of lung units are set in order to maximize gas exchange and minimize over-distension. The main goal is to titrate the optimal level of PEEP defined as the level of PEEP that allows the lowest FiO2 with an adequate level of oxygenation and avoiding complications induced by the level of PEEP. The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network have proposed to set individualized PEEP using a table that correlates the level of FiO2 and PEEP based on the oxygenation (Table 94.1) [3]‌. Titrating PEEP according to the ARDS Net PEEP-FiO2 ladder is strongly recommended. The benefit of PEEP might depend on the potential for alveolar recruitment. If the potential of recruitment is low, an increase in PEEP will not result in a beneficial effect on oxygenation with an accompanying higher risk for ventilator-induced lung injury, increased dead space that might potentially result in redistribution of pulmonary blood flow to non-ventilated regions of the lungs. If the increase of PEEP improves alveolar recruitment, the strain (distribution of pressure) might be reduced.

Table 94.1 National Heart, Lung, and Blood Institute (NHLBI) ARDS Clinical Trials Network FiO2/PEEP [3]‌

Lower PEEP group

FiO2

0.3

0.4

0.4

0.5

0.5

0.6

0.7

0.7

0.7

0.8

0.9

0.9

0.9

1.0

1.0

1.0

1.0

PEEP

5

5

8

8

10

10

10

12

14

14

14

16

18

18

20

22

24

Higher PEEP group

FiO2

0.3

0.3

0.4

0.4

0.5

0.5

0.6

0.6

0.7

0.8

0.8

0.9

1.0

1.0

PEEP

12

14

14

16

16

18

18

20

20

20

22

22

22

24

Adapted from New England Journal of Medicine, Brower RG et al., ‘Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome’, 351(4), pp. 327–36. DOI: 10.1056/NEJMoa032193. Copyright © 2004, Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

The potential for recruitment can be identified by the use of a ‘PEEP trial’. In a ‘PEEP trial’, the PEEP is progressively increased. Ideally, only one variable—the amount of PEEP—is altered during the trial, with VT, fraction of inspired oxygen (FiO2), body position, and other factors that might affect oxygenation unchanged. An assessment for both favourable and adverse PEEP effects should be made at each level as PEEP increased. As the condition of the patient may change over time, to determine the effects of PEEP most clearly the intervals at each level must be kept short. When the increase of PEEP is associated with an improvement of PaO2 and compliance and a decrease of PCO2, an alveolar recruitment is expected. Conversely, if the alveolar recruitment is not achieved, there is a minimal improvement of oxygenation by an increase in dead space. The PEEP trial should be performed in a systematic manner whenever feasible [4]‌.

It has been hypothesized that the level of PEEP can be determined by identifying pressure–volume (P–V) curve inflection points. Acquiring a dynamic curve presents the key to the curve’s bedside application. The lower inflection point (LIP) on the total respiratory system P–V curve is widely used to set PEEP in patients with acute respiratory failure (ARF) on the assumption that LIP represents alveolar recruitment However, it is becoming widely accepted that the upper inflection point (UIP) of the deflation limb of the P–V curve represents the point of optimal PEEP (Fig. 94.1). New methods used to identify optimal PEEP, including computed tomography (CT), transthoracic lung ultrasound (LUS) and active compliance measurements, are currently being investigated. Using CT, it is possible to assess the pulmonary distribution of the increase in gas volume resulting from tidal ventilation and PEEP and to separate PEEP-induced lung overdistension from alveolar recruitment. In the mid-1990s, Gattinoni et al. [5]‌ measured PEEP-induced alveolar recruitment on a single junta-diaphragmatic CT section by quantifying the decrease in non-aerated lung parenchyma characterized by CT attenuations ranging between −100 and +100 Hounsfield units (HU). In spite of the reference method for assessing PEEP-induced lung recruitment is lung CT, it is an important source of radiation, requires transporting an often unstable and hypoxaemic patient outside the ICU with a time-consuming analysis of data. Other considerations such as the stress index and the measurement of oesophageal pressure have been recently proposed to assess the level of PEEP to avoid overdistension.

Fig. 94.1 The hysteresis of the pressure–volume curve of the lung. On inflation limb lungs need higher pressures to inflate than on deflation. On deflation limb, the higher lung volume can be maintained on lower pressure. Thus, once the lung is open it is more compliant. At the lower inflection point the lung opens up, compliance improves, and at the upper inflection point optimal lung volume is achieved. At over inflation, compliance decreases and lung injury occurs. The upper inflection point of the deflation limb of the P–V curve represents the point of optimal PEEP.

Fig. 94.1 The hysteresis of the pressure–volume curve of the lung. On inflation limb lungs need higher pressures to inflate than on deflation. On deflation limb, the higher lung volume can be maintained on lower pressure. Thus, once the lung is open it is more compliant. At the lower inflection point the lung opens up, compliance improves, and at the upper inflection point optimal lung volume is achieved. At over inflation, compliance decreases and lung injury occurs. The upper inflection point of the deflation limb of the P–V curve represents the point of optimal PEEP.

Finally, some considerations on how to set the PEEP should be taken into account in patients with acute respiratory failure (ARF) due to acute exacerbation of chronic obstructive pulmonary disease (COPD). The application of low levels of PEEP can result useful in order to reduce the magnitude of the inspiratory effort during assisted MV (or pressure support) and weaning, and therefore intrinsic PEEP. The application of PEEP in COPD patients requires close monitoring of the end-expiratory lung volume by inspection of flow/volume curves during application of increasing levels of PEEP. The presence of dynamic hyperinflation and expiratory flow limitation can be suspected based on the shape of the expiratory limb of the flow/volume curve (Fig. 94.1).

Haemodynamic effects of PEEP

Based on a better understanding of heart and lung interactions, lung overdistension (with the consequent effect on the pulmonary circulation and thus on the right ventricle) might be present with the application of excessive tension and deformation of the lung tissues (Table 94.2). These effects are determined in part by the stress (transpulmonary pressure) and strain (ratio tidal volume and FRC) applied to about 480 million of alveoli and 30,000 cycles/days. The vast majority of the studies that found an inverse relationship between high levels of PEEP and RV function were conducted before the studies that proposed to limit the tidal volume in the patients with ARDS and therefore these patients were ventilated with tidal volumes higher than 10 mL/kg ideal body weight.

Table 94.2 Haemodynamic effects of PEEP

LV

  1. 1. ↓ Preload

    1. (a) ↓ in RV stroke volume:

      • ↑ Pulmonary vascular resistance

      • ↑ Pericardic pressure

    2. (b) ↓ LV telediastolic volume:

      • Ventricular interdependence

      • ↑ Pericardic pressure

    3. 2.Afterload: ↓ in LV transmural pressure

    4. 3. Contractility:↓ neurohormonal response?

Venous return

  1. 1.Pulmonary venous return (effect on RV)

    1. (a) ↓ RV preload

    2. (b) ↑ RV afterload (increased pulmonary vascular resistance)

RV

  1. 1.Venous return

    1. (a) ↑ Intrathoracic pressure

    2. (b) ↑ Pericardic pressure

    3. (c) ↑ RV pressure

    4. (d) ↓ Transmural RA pressure

  2. 2.Afterload

    1. (a) ↑ Pulmonary vascular resistance

    2. (b) Compression of peri-alveolar capillaries

  3. 3.Cardiac output

As end-expiratory, end-inspiratory, and mean airway pressures are all increased in the presence of PEEP, PEEP induces an increase in the intrathoracic pressure with several hemodynamic effects [6]‌. Despite extensive investigation, the effect of PEEP on human cardiac physiology is complex, unpredictable, and has not been totally defined. It may also elevate mean systemic pressure (PMS), the static circulatory filling pressure that is the upstream pressure for venous return. A PEEP level of less than 10 cmH2O rarely causes haemodynamic problems in the absence of intravascular volume depletion. The cardiodepressant effects of PEEP are often minimized with judicious intravascular volume support or cardiac inotropic support. Although peak pressure is related to the development of barotrauma, arterial hypotension is related to the mean airway pressure that may decrease venous return to the heart or decrease right ventricular function.

Except from the failing ventricle, PEEP usually decreases cardiac output. It is important to understand certain aspects of cardiac physiology to appreciate the effect of PEEP in cardiac output. Cardiac output is the product of heart rate and left ventricular stroke volume. In most pathophysiological states, stroke volume is the major determinant of cardiac output, while heart rate changes reflexively in response to changes in stroke volume. Stroke volume is influenced by four major factors:

  • Diastolic ventricular filling, termed preload.

  • Ventricular distensibility or compliance.

  • Ventricular contractility.

  • Ventricular afterload.

Preload and ventricular distensibility influence stroke volume by their effects on the heart during diastole, while contractility and afterload influence stroke volume during systole. At least three factors probably contribute to the decrease in cardiac output produced by PEEP decreased venous return (right ventricular filling), increased right ventricular afterload (regional or generalized lung overdistention can also stretch pulmonary vessels, which reduces their calibre and increases pulmonary vascular resistance) and decreased left ventricular distensibility (Fig. 94.2).

Fig. 94.2 Effect of positive end-expiratory pressure (PEEP) on left ventricular (LV) filling. See text.

Fig. 94.2 Effect of positive end-expiratory pressure (PEEP) on left ventricular (LV) filling. See text.

Abbreviation: LVEDV, left ventricular end-systolic volume.

Decreasing PEEP

If PEEP is reduced prematurely, some alveoli may remain sufficiently unstable to collapse, which worsens oxygenation. If this happens, PEEP higher than the previous baseline level may be required to reopen the collapsed alveoli and, conceivably, the patient’s requirement for MV may be unnecessarily prolonged.

Bacterial effects

The alveolar opening achieved with PEEP is likely to be responsible for this reduction in pneumonia risk, although the precise mechanism is unknown. PEEP is protective against pulmonary micro-aspiration by a protective counterbalance pressure. Various experimental studies have confirmed lower bacterial growth and a lower incidence of bacteraemia with strategies to maintain alveolar opening and reduce atelectasis after intratracheal instillation of bacteria into bronchial tree. The early application of PEEP in the non-hypoxaemic ventilated patients would stabilize the alveoli and can contribute to reducing the bacterial burden, and therefore the incidence of early-onset VAP.

Hormonal effects

PEEP induces a rapid and intense antidiuresis with fall in fractional excretion of sodium (FE Na+), whereas negative pressure breathing is associated with increased urinary flow. As discussed before, PEEP has haemodynamic effects, but also leads to indirect cardiovascular reflex activation or deactivation of high and low pressure baroreflexes, and to vasoactive hormonal release of antidiuretic hormone (ADH), renin, and norepinephrine.

Contraindications

There are no absolute contraindications to applied PEEP. However, applied PEEP can have adverse consequences (especially at high levels) and should be used cautiously in patients with unilateral lung disease, obstructive lung disease (without the presence of expiratory flow limitation), elevated peak and mean airway pressures, bronchopleural fistulae, hypovolaemia, elevated intracranial pressure, and pulmonary embolism (PEEP can worsen hypoxaemia in pulmonary embolism when adjacent unobstructed pulmonary vessels become compressed).

Complications

A classic paradigm of MV is that the systemic hypotension induced ventilation failure to produce the right ventricle (RV), and that this associated with high pressure and mainly with the use of PEEP. This paradigm comes from classical studies in which objective a progressive elevation of PEEP is associated with a progressive increase in central venous pressure and a fall in blood pressure. Thus, in clinical practice, it is common to have episodes of hypotension in a mechanically-ventilated patient. Between the responses are initial therapeutic volume expansion, initiation, or dose increase of inotropic agents, the reduction in the dose of sedatives and also the descent PEEP level with the intention of reducing the pressure intrathoracic. The possibility of right ventricular failure due to pulmonary hypertension, with a drop in systemic blood pressure related to the elevation of PEEP, is mainly produced in many situations with other conditions, such as hypovolaemia, the appearance of comorbid conditions that decrease the compliance lung (increased intra-abdominal pressure, restrictive lung disease, presence of auto-PEEP or pneumothorax) and the inappropriate use of appropriate modes of ventilation.

Another important point when PEEP is applied is the possibility to produce barotrauma. Pulmonary barotrauma is lung injury that results from the hyperinflation of alveoli past the rupture point. The most severe form is the development of pneumothorax, pneumomediastinum and subcutaneous emphysema.

References

1. Determann RM, Royakkers A, Wolthuis EK, et al. (2010). Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Critical Care, 14(1), R1.Find this resource:

2. Briel M, Meade M, Mercat A, et al. (2010). Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. Journal of the American Medical Association, 303(9), 865–73.Find this resource:

3. Brower RG, Lanken PN, MacIntyre N, et al. (2004). Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. New England Journal of Medicine, 351(4), 327–36.Find this resource:

4. Meade MO, Cook DJ, Guyatt GH, et al. (2008). Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. Journal of the American Medical Association, 299(6), 637–45.Find this resource:

5. Gattinoni L, Pelosi P, Crotti S, and Valenza F. (1995). Effects of positive end-expiratory pressure on regional distribution of tidal volume and recruitment in adult respiratory distress syndrome. American Journal of Respiratory and Critical Care Medicine, 151(6), 1807–14.Find this resource:

6. Luecke T and Pelosi P. (2005). Clinical review: positive end-expiratory pressure and cardiac output. Critical Care, 9(6), 607–21.Find this resource: