Positive End-Expiratory Pressure: Physiological Effects

Positive end-expiratory pressure changes the state from which every ventilator breath begins. It can preserve aeration, alter gas exchange, and change the loading of both ventricles. Its usefulness depends on the balance of these effects in the current patient.

26.1 PEEP Maintains Pressure at the End of Expiration

Positive end-expiratory pressure, or PEEP, is the pressure maintained at the airway opening above the chosen pressure reference at the end of expiration. In most ventilator displays, that reference is atmospheric pressure. PEEP prevents the airway pressure from returning to zero during expiration; it does not necessarily stop expiratory flow or keep every region of the lung open.

The applied pressure changes the equilibrium between the lung's inward recoil and the pressures surrounding it. End-expiratory lung volume often increases. How much it increases depends on lung and chest-wall mechanics, airway closure, recruitment, and whether expiration has enough time to finish.

The displayed setting describes external PEEP imposed by the ventilator. Total end-expiratory pressure can be higher if gas remains trapped behind resistance or expiratory flow limitation. In a passive patient, an appropriately performed end-expiratory hold can estimate total PEEP in communicating regions. The difference from external PEEP is commonly described as intrinsic PEEP.

A single measurement still averages a heterogeneous system. Closed airways may prevent pressure equilibration with trapped regions. Active expiratory muscle contraction can also affect the reading. A measured value should therefore be interpreted with the waveform, timing, and patient's muscle activity.

PEEP also changes the pressure sequence over the whole respiratory cycle. With tidal volume held constant, a higher starting pressure usually increases end-inspiratory pressure unless compliance improves sufficiently. In pressure-controlled ventilation, the meaning depends on whether the inspiratory setting is specified above PEEP or as an absolute pressure. An unnoticed difference in those conventions can change delivered volume.

Early physiological work by Falke and colleagues examined lung volume, mechanics, gas exchange, and circulation together during PEEP changes in severe acute respiratory failure. The study's lasting lesson is the need to measure the combined cardiopulmonary response rather than interpret the pressure setting as having one isolated effect. 1

26.2 A Larger End-Expiratory Volume Can Have Different Meanings

Increasing PEEP can add gas volume by opening previously unaerated regions, expanding regions that were already aerated, or both. Recruitment and distension therefore contribute in different proportions. A measured increase in end-expiratory lung volume does not identify those proportions on its own.

When new tissue remains aerated at expiration, the next breath can be distributed over a larger participating lung. Some regions may undergo less repeated opening and closing. At a fixed tidal volume, respiratory-system compliance may improve if recruitment adds expandable tissue without an offsetting loss of compliance elsewhere.

Already open regions also receive the higher pressure. Their resting volume can increase even when little new tissue is recruited. If they approach a less compliant part of their pressure–volume relationship, further volume requires a larger pressure increment. This can increase end-inspiratory loading and divert ventilation away from some regions.

The response depends on starting conditions. A region compressed by surrounding tissue may recruit over one pressure interval. A flooded or consolidated region may remain unaerated despite a larger pressure increase. Airway opening and tissue recruitment can also occur at different pressures, so the airway pressure does not identify one alveolar opening threshold.

Time matters as well. Some changes occur rapidly, while redistribution and slow opening continue afterward. Disconnection, suctioning, position, and the preceding inflation history can change the apparent response. Comparing measurements obtained at different times or after different maneuvers can misattribute a change to the PEEP setting alone.

These mechanisms explain why neither the largest lung volume nor the best compliance is a complete objective by itself. More volume may represent useful recruitment or excessive distension. Improved global compliance may conceal a mixture of recruitment in one region and overdistension in another.

The practical interpretation should specify what changed and what remains uncertain. A larger end-expiratory volume with lower tidal driving pressure suggests a different mechanical response from a larger volume with rising driving pressure. Regional information and cardiovascular tolerance help determine the meaning of either pattern.

26.3 Better Oxygenation Does Not Necessarily Mean Better Oxygen Delivery

PEEP can improve oxygenation when it opens perfused lung units that previously received little ventilation. More blood then passes through gas-exchanging regions rather than leaving poorly oxygenated. Maintaining aeration between breaths can preserve this reduction in shunt.

Other effects complicate the interpretation. PEEP can redistribute pulmonary blood flow and change cardiac output. Mixed venous oxygen content can change as systemic oxygen extraction changes. Consequently, a rise in arterial oxygen tension or saturation does not quantify anatomical recruitment or demonstrate improved tissue oxygen supply.

Systemic oxygen delivery depends on both arterial oxygen content and blood flow. Hemoglobin-bound oxygen usually contributes most of the arterial content. An illustrative simplified calculation makes the dependence clear.

Here hemoglobin is in g/dL, saturation is a fraction, content is in mL O₂/dL, and cardiac output is in L/min. The factor 1.34 approximates the milliliters of oxygen carried per gram of fully saturated hemoglobin. The factor 10 converts liters to deciliters. The first expression omits dissolved oxygen, which must be included when its contribution is relevant. These examples assume hemoglobin remains 10 g/dL.

Before a PEEP change, let saturation be 0.90 and output be 5 L/min. Content is approximately 1.34 × 10 × 0.90 = 12.06 mL O₂/dL. Delivery is 5 × 12.06 × 10 = 603 mL O₂/min. If saturation rises to 0.96 but output falls to 4 L/min, content becomes 1.34 × 10 × 0.96 = 12.864 mL O₂/dL. Delivery becomes 4 × 12.864 × 10 ≈ 515 mL O₂/min.

The higher saturation coexists with lower calculated global oxygen delivery. The values are illustrative rather than treatment targets. They show why a gas-exchange benefit must be interpreted alongside flow and perfusion.

PEEP can also alter carbon dioxide elimination. Recruitment may improve ventilation of perfused units. Excessive expansion can compress pulmonary vessels and increase ventilation relative to perfusion, contributing to dead-space ventilation. A change in arterial carbon dioxide therefore requires consideration of minute ventilation, perfusion, metabolic production, and timing, rather than one explanation such as recruitment failure.

26.4 Pulmonary Vascular Effects Change Right Ventricular Load

Pulmonary vessels respond to lung inflation in different ways. Vessels within alveolar walls can be compressed as alveolar pressure and expansion increase. Extra-alveolar vessels are influenced by surrounding tissue pressure and radial traction from the expanding parenchyma. These mechanisms help explain why pulmonary vascular resistance is not a simple linear function of lung volume.

At low volumes, narrowed extra-alveolar vessels, hypoxic vasoconstriction, and poorly aerated regions can increase vascular load. Recruitment and improved oxygenation may reduce some of these effects. At high volumes, compression and elongation of vessels in expanded regions can instead increase resistance to right ventricular ejection.

The familiar U-shaped relation between lung volume and pulmonary vascular resistance is a conceptual description of these competing effects. Its minimum is not a bedside PEEP prescription. Injury, vascular obstruction, regional overdistension, and pulmonary arterial and venous pressures change the relationship.

The right ventricle must generate flow against the resulting pulmonary vascular load. An increase in load can reduce stroke volume and cause dilation. If the ventricle dilates within the pericardial constraint, septal displacement can impair left ventricular filling. Systemic arterial pressure may then fall even though measured right-sided filling pressure rises.

Schmitt and colleagues assessed right ventricular outflow impedance during PEEP titration in ARDS using pulmonary artery Doppler measurements. Their physiological study showed that right ventricular loading can respond differently to different ways of selecting PEEP. This supports assessing the right ventricle during titration; it does not establish a universally optimal setting or a survival-improving Doppler target. 2

A fall in output after PEEP can therefore arise from more than reduced venous return. Excessive pulmonary vascular loading may be the dominant problem, particularly in a vulnerable right ventricle. Additional fluid can raise venous congestion without restoring effective ejection if the main limitation is afterload.

Interpret cardiac imaging with the ventilatory change, blood gases, rhythm, and perfusion. A pressure change that improves lung mechanics but causes important right ventricular deterioration represents a mixed response requiring reassessment.

26.5 Venous Return Depends on More Than the Rise in CVP

Systemic venous return is commonly described by the pressure difference between mean systemic filling pressure and right atrial pressure, divided by resistance to venous return. Mean systemic filling pressure represents the pressure generated by the systemic vascular volume and its distribution under no-flow conditions. It is not the mean arterial pressure.

This is a simplified circulation model. Regional vascular collapse and changing external pressures can make the effective downstream conditions more complex than one right atrial pressure. The equation is useful only when its pressure references and assumptions are kept consistent.

Raising intrathoracic pressure can raise measured right atrial pressure and oppose inflow. However, pressure transmission to the abdomen and systemic veins can also raise upstream pressure or alter resistance. The change in CVP alone therefore does not determine the change in the venous-return gradient.

Jellinek and colleagues examined positive airway pressure during a specialized human physiological study performed during defibrillator implantation. Both right atrial and estimated mean systemic filling pressure rose, while stroke volume fell. The estimated gradient was relatively preserved. This selected setting demonstrates why a rise in right atrial pressure cannot be interpreted in isolation; it does not reproduce every mechanism present during ICU PEEP titration. 3

The patient's vascular state changes the response. A circulation with little recruitable stressed volume may be sensitive to altered intrathoracic conditions. Venous tone, abdominal pressure, and regional flow limitations can modify that sensitivity. Concurrent vasoactive treatment can also change the upstream pressure and resistance while PEEP changes.

A fall in output after a ventilator adjustment should therefore prompt examination of timing and mechanism. It may reflect impaired inflow, increased right ventricular afterload, or both. A rising CVP is compatible with several of these conditions and is not proof that the right ventricle has received more useful preload.

The same reasoning limits a routine fluid response. Some patients may benefit from additional vascular volume, while others mainly develop higher filling pressures and congestion. Assess preload responsiveness and fluid tolerance in the context of the identified ventilatory mechanism.

26.6 Measured Filling Pressure and Transmural Pressure Can Move Differently

A catheter measures pressure within a chamber relative to its reference. The pressure stretching the chamber wall is the internal pressure minus the surrounding pressure. This is transmural pressure. PEEP can raise the surrounding thoracic pressure, so measured intracardiac pressure may rise while the pressure distending the chamber changes little or falls.

For an illustrative right atrial pressure of 10 cm H₂O and surrounding pressure of 6 cm H₂O, transmural pressure is 10 − 6 = 4 cm H₂O. After a ventilatory change, suppose the measured right atrial pressure is 15 cm H₂O and surrounding pressure is 12 cm H₂O. The transmural value is now 15 − 12 = 3 cm H₂O. The catheter pressure rose by 5, while the calculated distending pressure fell by 1 cm H₂O.

These values explain a pressure relationship, not a method for deriving every patient's right atrial preload. Surrounding pressure is difficult to measure, varies regionally, and includes pericardial influences. A fixed fraction of airway PEEP cannot be subtracted from every CVP to obtain an accurate transmural value.

The left ventricle also responds to surrounding pressure. Raising intrathoracic pressure can reduce the transmural pressure the ventricle must generate to eject into the systemic circulation. This can reduce an important component of left ventricular afterload. The benefit may be relevant when left ventricular failure and high ejection load are prominent.

At the same time, reduced right ventricular output lowers subsequent left ventricular filling. Right ventricular dilation and septal displacement can further constrain the left ventricle. The net cardiac response depends on whether reduced ejection load outweighs impaired filling and other adverse effects.

Jardin and colleagues studied ventricular volumes and pressures during PEEP in ARDS, demonstrating the importance of ventricular loading and interaction when interpreting reduced left ventricular output. Their selected physiological study should not be read as evidence that every patient with left ventricular disease has the same response. 4

This is why PEEP cannot be classified as uniformly harmful or beneficial to cardiac function. Identify the ventricle and loading condition being changed, then observe output and perfusion. Pressure measurements are useful only when their surrounding-pressure context is understood.

26.7 External and Intrinsic PEEP Interact According to Expiratory Mechanics

Intrinsic PEEP develops when expiration does not fully empty the communicating lung before the next breath, or when airway closure retains gas. It often accompanies dynamic hyperinflation in obstructive disease. A high end-expiratory volume can therefore exist despite a modest external PEEP setting.

Before inspiratory flow begins, an actively breathing patient may need to lower alveolar pressure enough to overcome the difference between trapped alveolar pressure and the airway opening. This creates an inspiratory threshold load. Part of the effort may produce no ventilator-delivered flow and can appear as ineffective triggering.

External PEEP can reduce that threshold difference in some patients with expiratory flow limitation. Under those conditions, increasing airway-opening pressure within a limited range may not increase upstream alveolar pressure by the same amount. The response resembles a downstream pressure change below a flow-limiting segment.

The protection is conditional. If there is no relevant flow limitation, if external pressure exceeds the effective limiting pressure, or if regional behavior differs, added PEEP can increase end-expiratory volume and worsen hyperinflation. Intrinsic and external PEEP are therefore not two independent numbers that can always be added without changing the system.

Ranieri and colleagues studied external PEEP in mechanically ventilated patients with COPD and acute ventilatory failure. Their physiological findings support the importance of flow limitation in determining whether applied PEEP adds hyperinflation. They do not supply a universally safe fraction of measured intrinsic PEEP for all obstructive patients. 5

Evaluate the effect on total PEEP, expiratory flow, delivered volume, effort, and circulation. A more comfortable trigger can coexist with harmful additional inflation if the rest of the response is not examined. Regional trapping can also remain hidden behind an apparently modest global measurement.

The underlying causes of incomplete expiration still require attention. Resistance, expiratory time, minute-ventilation demand, and airway patency influence how much gas remains. External PEEP may address a threshold load without correcting those causes. The detailed management of dynamic hyperinflation follows from these mechanisms and requires its own assessment.

26.8 Assess a PEEP Change With Paired Measurements

A physiological assessment begins with a clear reason for the change. The aim may be to improve oxygenation, maintain recruitment, reduce a threshold load, or modify cardiac loading. The measurements needed to evaluate success depend on that aim.

Compare conditions before and after the change while accounting for other interventions. Tidal volume, respiratory rate, oxygen fraction, patient effort, position, sedation, and vasoactive treatment can all modify the apparent response. A simultaneous change makes attribution less certain, even when the new state is clinically preferable.

For lung mechanics, compare total PEEP, plateau pressure, driving pressure, and delivered volume when the patient and measurement conditions permit. Check whether the rise in end-inspiratory pressure is proportionate to the end-expiratory change. A falling driving pressure at fixed volume can support improved tidal compliance, but it does not establish uniform recruitment or lower total lung inflation.

For gas exchange, compare oxygenation at a known oxygen fraction and consider carbon dioxide, minute ventilation, and dead-space behavior. A short-lived saturation rise immediately after a maneuver is different from sustained improvement under the maintained setting. Poor pulse-oximeter signals during peripheral vasoconstriction also require confirmation.

For circulation, follow arterial pressure, stroke volume or output when available, peripheral perfusion, and relevant cardiac imaging. A maintained pressure achieved by increasing vasopressor support does not demonstrate unchanged cardiovascular tolerance. Likewise, a rise in CVP cannot distinguish pressure transmission from a failing right ventricle.

Regional tools can explain a mixed response. New dependent ventilation with increasing nondependent overdistension, for example, may account for little change in global compliance. Esophageal pressure can add chest-wall information when appropriately measured. Neither tool removes the need to assess hemodynamic consequences.

Reassessment requires an interval appropriate to the question. Abrupt cardiovascular deterioration deserves immediate attention, while some recruitment and gas-exchange effects evolve more slowly. Repeatedly changing settings before the response can be interpreted may create a sequence of numbers without a clear physiological explanation.

26.9 Higher- and Lower-PEEP Trials Tested Different Strategies

Comparing trial results requires examining how PEEP was selected and what accompanied it. A pressure–oxygen table, a plateau-pressure approach, and an intensive recruitment protocol are different interventions. They should not be treated as interchangeable tests of a single higher-PEEP treatment.

ALVEOLI compared higher and lower PEEP/oxygen strategies in patients receiving low tidal volumes and a plateau-pressure limit. Overall clinical outcomes were similar between groups. The trial does not establish that every patient responds equally to PEEP; it tests the assigned strategies in the enrolled population. 6

LOVS compared an open-lung strategy incorporating higher PEEP and recruitment maneuvers with a control strategy, both targeting low tidal volumes. Hospital mortality was not significantly different, although some hypoxemia-related outcomes favored the intervention. Those physiological and rescue-therapy findings are distinct from a demonstrated survival benefit. 7

EXPRESS compared a minimal-distension approach with a strategy that increased PEEP toward a defined plateau-pressure range. The higher-PEEP strategy improved some secondary outcomes, including ventilator-free days, without a significant difference in the primary 28-day mortality outcome. This result does not make the trial's plateau-pressure range an individual patient's proven optimum. 8

Briel and colleagues pooled individual-patient data from these major trials. The overall mortality comparison was not statistically significant. They found evidence that the effect of higher PEEP differed according to oxygenation severity, with a possible benefit in the subgroup meeting the study's ARDS oxygenation criterion. This supports considering illness severity in interpreting the average trial result. It does not establish that oxygenation severity directly measures recruitability or identifies one best PEEP. 9

ART subsequently tested an intensive recruitment and compliance-titrated PEEP strategy and found increased mortality and barotrauma. That finding limits the strategy tested rather than proving that every increase in maintained PEEP is harmful. It also prevents using a better compliance or oxygenation response as sufficient justification for an aggressive protocol. 10

Across these studies, the relevant interpretation is the whole treatment strategy, population, comparator, and outcome. Neither an average neutral result nor a favorable subgroup authorizes a universal bedside setting.

26.10 Guidance Provides a Starting Framework, Not an Individual Optimum

Guidelines integrate results across trials and weigh benefits, harms, and certainty. Their recommendations address patient groups and treatment strategies. They do not directly measure the balance of recruitment, distension, and cardiovascular effects in one patient.

The 2026 Surviving Sepsis Campaign conditionally suggests higher rather than lower PEEP for adults with sepsis and moderate to severe ARDS, with moderate-certainty evidence. The same guideline strongly recommends against an incremental PEEP-titration strategy in that population, also with moderate certainty. These recommendations have different targets and should not be collapsed into an instruction to keep increasing PEEP. 11

The population restriction matters. This statement does not establish the same approach for every postoperative patient, every patient with mild lung injury, or every patient with obstructive hyperinflation. Those settings differ in mechanisms and in the supporting evidence.

A protocol can provide a reproducible starting approach and help avoid arbitrary changes. Its selection rule still needs to be understood. Oxygen-based tables respond to a gas-exchange requirement; pressure-based approaches constrain a mechanical variable. Neither automatically proves anatomical recruitment or cardiovascular tolerance.

Similarly, a monitor-derived optimum is an optimum for its selected measurement under the conditions sampled. Best global compliance may occur despite regional overdistension. Best oxygenation may coexist with lower output. A favorable esophageal-pressure estimate may not characterize all pleural regions. The word best must always identify the variable being optimized.

Clinical reassessment therefore operates alongside the evidence framework. Unexpected hypotension, worsening right ventricular function, increasing dead space, or unfavorable mechanics can change the balance for a particular patient. Conversely, reducing PEEP without considering derecruitment may sacrifice useful aeration.

The purpose of physiology is to explain these individual responses and detect intolerance. The purpose of outcome evidence is to define what can be claimed about the strategy. Combining them supports a defensible decision without pretending that one variable supplies a universal prescription.

26.11 Integrating a Mixed Pulmonary and Circulatory Response

Consider an illustrative patient with moderate to severe ARDS receiving passive ventilation. PEEP is increased because of persistent hypoxemia. Oxygenation improves and driving pressure decreases at the same tidal volume, but cardiac output falls and the right ventricle enlarges.

The pulmonary findings support a potentially useful change in tidal mechanics and gas exchange. They do not establish that all additional volume represents recruitment. The cardiac findings raise concern that increased pulmonary vascular load or altered filling has become important. The response is mixed rather than simply successful or unsuccessful by one number.

Confirm the comparison first. Check the pressure measurements, total PEEP, volume delivery, rhythm, effort, and timing. Review whether vasoactive treatment, position, or other settings changed. An apparent output fall based only on a tone-sensitive monitor may need corroboration.

Then identify the dominant limiting mechanism. A dilating right ventricle with worsening ejection suggests a different problem from a small underfilled right ventricle with preserved contraction. Rising venous pressure with impaired organ drainage adds further consequences. The same fluid intervention cannot be assumed to solve both patterns.

A useful reassessment examines how the pulmonary benefit changes as the circulatory limitation is addressed. The aim is to maintain adequate gas exchange and useful aeration while preserving forward flow. Chasing the maximal oxygenation response can miss the point at which its additional cardiovascular effects outweigh the gain.

Later, resolving edema, a position change, or recovery of spontaneous breathing alters the starting state again. A previously tolerated PEEP may contribute to hyperinflation or excess loading as the lung improves. Alternatively, reducing it may reveal persistent closure and produce deterioration. Earlier tolerance does not guarantee that the setting remains appropriate indefinitely.

PEEP is therefore an ongoing influence on both respiratory and circulatory physiology. Its assessment requires explaining where the added pressure goes, what volume it maintains, how it affects blood flow, and whether the resulting state continues to meet the patient's needs.

References

1. Falke KJ, Pontoppidan H, Kumar A, Leith DE, Geffin B, Laver MB. Ventilation with end-expiratory pressure in acute lung disease. J Clin Invest. 1972;51(9):2315–2323. doi:10.1172/JCI107042

2. Schmitt JM, Vieillard-Baron A, Augarde R, Prin S, Page B, Jardin F. Positive end-expiratory pressure titration in acute respiratory distress syndrome patients: impact on right ventricular outflow impedance evaluated by pulmonary artery Doppler flow velocity measurements. Crit Care Med. 2001;29(6):1154–1158. doi:10.1097/00003246-200106000-00012

3. Jellinek H, Krenn H, Oczenski W, Veit F, Schwarz S, Fitzgerald RD. Influence of positive airway pressure on the pressure gradient for venous return in humans. J Appl Physiol. 2000;88(3):926–932. doi:10.1152/jappl.2000.88.3.926

4. Jardin F, Farcot JC, Boisante L, Curien N, Margairaz A, Bourdarias JP. Influence of positive end-expiratory pressure on left ventricular performance. N Engl J Med. 1981;304(7):387–392. doi:10.1056/NEJM198102123040703

5. Ranieri VM, Giuliani R, Cinnella G, et al. Physiologic effects of positive end-expiratory pressure in patients with chronic obstructive pulmonary disease during acute ventilatory failure and controlled mechanical ventilation. Am Rev Respir Dis. 1993;147(1):5–13. doi:10.1164/ajrccm/147.1.5

6. Brower RG, Lanken PN, MacIntyre N, et al.; 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. N Engl J Med. 2004;351(4):327–336. doi:10.1056/NEJMoa032193

7. Meade MO, Cook DJ, Guyatt GH, et al.; Lung Open Ventilation Study Investigators. 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. JAMA. 2008;299(6):637–645. doi:10.1001/jama.299.6.637

8. Mercat A, Richard JC, Vielle B, et al.; Expiratory Pressure (Express) Study Group. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299(6):646–655. doi:10.1001/jama.299.6.646

9. Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303(9):865–873. doi:10.1001/jama.2010.218

10. Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators; Cavalcanti AB, Suzumura EA, et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2017;318(14):1335–1345. doi:10.1001/jama.2017.14171

11. Society of Critical Care Medicine and European Society of Intensive Care Medicine. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. Official recommendations