PEEP, Intrathoracic Pressure, and Right Ventricular Afterload

Positive end-expiratory pressure changes both the pressure surrounding the heart and the volume of the lung through which the right ventricle ejects. These effects can oppose one another. Recruitment may improve oxygenation and relieve vascular compression in one region, while distension impedes blood flow elsewhere. This chapter develops the circulatory consequences of PEEP, building on the respiratory mechanics of Chapters 23 and 26 and the oxygen-transport principles of Chapter 34.

40.1 Applied PEEP and Total PEEP Describe Different Starting Conditions

Applied, or extrinsic, PEEP is the pressure maintained at the airway opening by the ventilator during expiration. It is generally displayed in cm H₂O relative to atmospheric pressure. Intrinsic PEEP is pressure retained because expiration is incomplete. Total PEEP incorporates the externally maintained pressure and the intrinsic component present under the measurement conditions.

In a passive patient, an end-expiratory occlusion allows pressure to equilibrate between communicating alveoli and the airway sensor. Suppose applied PEEP is 8 cm H₂O and the occlusion pressure is 12 cm H₂O. The measured intrinsic component is 12 − 8 = 4 cm H₂O. The circulation experiences the mechanical consequences of the resulting thoracic state, rather than the displayed setting in isolation.

An occlusion does not necessarily reveal every trapped region. Airway closure can isolate units, unequal time constants can delay equilibration, and expiratory muscle activity can add pressure. A seemingly modest measured intrinsic PEEP therefore cannot exclude important regional hyperinflation.

Applied and intrinsic PEEP also interact. In flow-limited obstructive lungs, increasing downstream airway pressure may initially leave upstream pressure and end-expiratory volume nearly unchanged. Once the relevant limiting conditions are exceeded, additional external pressure may increase retained volume and circulatory impairment. Ranieri and colleagues demonstrated this behavior in ventilated patients with COPD. Their group observations do not establish a universal fraction of intrinsic PEEP that is safe for every patient. 1

Pressure units require attention when connecting ventilator and vascular measurements. One mm Hg is approximately 1.36 cm H₂O; conversely, 10 cm H₂O is approximately 7.4 mm Hg. Pressures must be converted before subtraction. The resulting difference still requires an explanation of which compartments were measured and at what respiratory phase.

40.2 Added Airway Pressure Is Partitioned Between Lung and Chest Wall

Under static conditions in communicating units, alveolar pressure approximates airway pressure. Transpulmonary pressure is alveolar pressure minus pleural pressure. It is the pressure across the lung, whereas pleural pressure contributes to the pressure surrounding intrathoracic vessels and the heart. These are different mechanical exposures.

For a passive respiratory system, the pressure needed to increase volume is shared between lung recoil and chest-wall recoil. A relatively stiff chest wall requires a larger surrounding-pressure change for a given volume increase. A relatively stiff lung requires a larger transpulmonary change. Chiumello and colleagues demonstrated substantial variation in the relationship between airway pressure and lung stress across patients and ventilatory conditions. 2

An illustrative pressure change makes the partition clear. Total PEEP increases by 6 cm H₂O, and a valid end-expiratory esophageal measurement increases by 2 cm H₂O. If esophageal change reasonably represents the relevant pleural change, the estimated transpulmonary increase is 6 − 2 = 4 cm H₂O. In another mechanical configuration, a surrounding-pressure increase of 4 cm H₂O would leave only 2 cm H₂O of the same airway increment across the lung.

These illustrative examples show pressure partitioning; they are not correction rules. Recruitment, nonlinear recoil, abdominal displacement, posture, and regional pleural gradients can change the relationship during the adjustment. A fraction estimated during tidal inflation need not describe the pressure transmission of a larger PEEP change.

Esophageal pressure adds information when position, balloon filling, calibration, and pressure transmission have been assessed. It does not sample a uniform pressure surrounding every vessel or cardiac chamber. Consequently, neither subtracting all PEEP nor subtracting a fixed fraction of it from a filling pressure provides a universally valid estimate. Chapter 41 develops cardiac transmural pressure in greater detail.

40.3 A Larger End-Expiratory Volume Can Recruit or Overdistend

Increasing PEEP usually raises end-expiratory lung volume, but the added gas can enter different anatomical destinations. Recruitment restores aeration to previously closed or poorly aerated tissue. Distension enlarges units that were already open. Both processes can occur simultaneously, with recruitment in dependent regions and excess distension in less dependent regions.

The distinction matters to pulmonary vessels. Opening a compressed region can restore vascular pathways and improve local oxygenation. Distending an already inflated region can narrow capillaries within its alveolar walls and divert blood elsewhere. The same increase in total lung volume can therefore produce different pulmonary vascular effects depending on its regional distribution.

Gattinoni and colleagues used computed tomography to show wide variation in potentially recruitable tissue among patients with acute lung injury or ARDS. Their findings help explain why the same airway-pressure intervention has different consequences. Recruitability assessed with a particular imaging protocol is not identical to the amount of useful recruitment achieved by a bedside PEEP change. 3

Respiratory-system compliance can improve when newly aerated tissue accepts tidal volume more easily. It can worsen when distension moves open tissue onto a stiffer portion of its pressure–volume relationship. However, chest-wall changes, airway closure, and heterogeneous regional behavior can complicate either interpretation. A favorable global compliance change cannot prove that no region is overdistended.

Volume history also matters. Tissue opened during a preceding inflation may remain aerated at a pressure that would not have opened it initially. Thus a pressure–volume response on deflation can differ from the response during inflation. PEEP is acting on a lung with a history, not on a fixed spring.

The circulatory interpretation follows the regional mechanism: which vessels reopen, which are compressed, how much pleural pressure rises, and whether the right ventricle can sustain flow through the resulting vascular network.

40.4 Venous Return Depends on Upstream Pressure and Collapsible Pathways

Raising pressure around the right atrium commonly raises measured right atrial pressure. If the upstream systemic filling pressure did not change, the pressure gradient for venous return would fall. Mean systemic filling pressure describes the systemic vascular pressure after flow has stopped and pressures have equilibrated; it reflects stressed blood volume and vascular capacitance rather than a directly measured pressure in one peripheral vein.

In a simplified steady model, venous return depends on the difference between mean systemic filling pressure and right atrial pressure, divided by resistance to venous return. Suppose upstream pressure is 18 mm Hg, right atrial pressure is 8 mm Hg, and resistance is 2 mm Hg·min/L. The gradient is 10 mm Hg and modeled flow is 10/2 = 5 L/min. If right atrial pressure rises to 12 while upstream pressure rises to 20, the gradient becomes 8 and flow becomes 4 L/min, assuming unchanged resistance.

The upstream response cannot be ignored. PEEP can redistribute blood, alter vascular capacitance, and activate reflexes. Fessler and colleagues showed in dogs that mean systemic pressure could rise substantially with PEEP, sometimes preserving the measured filling-pressure gradient despite reduced flow. This demonstrates why the rise in right atrial pressure alone is an incomplete explanation. 4

The pathways are also collapsible. At a compressed segment, surrounding pressure can become the effective downstream limit. Further lowering right atrial pressure then fails to increase flow. Subsequent canine venous-bypass experiments demonstrated PEEP-related changes in critical closing behavior and venous conductance, beyond changes in the simple upstream–atrial gradient. 5

Diaphragmatic displacement and abdominal pressure add another interaction. Compression of abdominal capacitance vessels can raise upstream pressure or displace blood centrally. It can also impede caval flow, increase resistance, and impair abdominal organ drainage. The net result depends on volume, vascular tone, surrounding pressure, and the anatomical site of compression. Abdominal pressure is therefore neither a guaranteed compensation nor an inevitable explanation for every output fall.

40.5 Lung Inflation Exerts Opposing Effects on Pulmonary Vessels

Pulmonary vessels embedded in alveolar walls behave differently from vessels supported by surrounding parenchyma. Alveolar vessels are exposed to the forces produced as alveoli inflate. At high distension, capillaries can become elongated and narrowed, increasing resistance to flow. Their behavior depends on vascular pressure relative to the surrounding mechanical forces.

Extra-alveolar vessels receive outward traction from the expanding lung. At low lung volume, reduced traction can narrow them. Inflation can enlarge these pathways and reduce their resistance. The opposing tendencies explain the familiar curved relationship between lung volume and total pulmonary vascular resistance: resistance may increase at both low and high volumes, through different mechanisms.

This is a conceptual relationship, not a bedside prescription to restore one universal volume. Whittenberger and colleagues demonstrated inflation-dependent vascular resistance in controlled canine preparations, including effects of blood flow and volume history. The behavior of an injured, edematous, heterogeneously aerated lung cannot be reduced to one unchanging curve. 6

Regional pressure relationships further modify flow. When pulmonary venous pressure exceeds alveolar pressure, changes in downstream venous pressure can influence the driving gradient. When alveolar pressure exceeds venous pressure in a collapsible region, alveolar pressure can become the effective downstream constraint. West, Dollery, and Naimark demonstrated these relationships in isolated perfused lungs. Their zones describe regional mechanical conditions, not permanently assigned anatomical compartments. 7

Increasing PEEP can therefore improve flow through a previously compressed low-volume region while impairing flow through an overdistended region. Reduced vascular pressure during hypovolemia or RV failure makes alveolar compression more likely at a given alveolar pressure. Conversely, higher vascular pressure can distend vessels, although it may carry other consequences, including edema and increased RV loading.

40.6 Pulmonary Arterial Pressure Must Be Interpreted With Flow

RV afterload is the load opposing ejection. Pulmonary vascular resistance, or PVR, describes its mean resistive component. The conventional calculation subtracts pulmonary artery wedge pressure, PAWP, from mean pulmonary arterial pressure, mPAP, and divides by cardiac output, Q. With pressures in mm Hg and flow in L/min, the result is in Wood units.

Consider an illustrative state with mPAP 35 mm Hg, PAWP 15 mm Hg, and flow 5 L/min. The pressure difference is 20 mm Hg, and calculated PVR is 20/5 = 4 Wood units. After a PEEP change, suppose mPAP falls to 30, PAWP remains 15, and flow falls to 3. The difference is now 15, but PVR is 15/3 = 5 Wood units. A lower pulmonary arterial pressure has accompanied a higher calculated resistance because the ventricle is delivering less flow.

This example does not establish that resistance caused the entire output fall. Venous return may also have changed. It demonstrates why pulmonary arterial pressure alone cannot describe the response. A failing RV may generate less pressure even as its coupling to the pulmonary circulation deteriorates.

The conventional calculation also assumes that PAWP appropriately represents downstream pressure. Regional vascular waterfalls can make that assumption incomplete. Pulmonary vessels recruit and distend as flow and pressure change, so a single pressure–flow quotient is not a complete pressure–flow curve. External pressure and the respiratory phase affect the measured pressures as well.

Direct physiological studies show that ventilator settings can change RV outflow behavior. Schmitt and colleagues compared PEEP selected from a pressure–volume inflection point with a compliance-based condition in ARDS. The former improved oxygenation more but impaired RV ejection more. These Doppler observations clarify a mechanism without establishing a universally optimal Doppler target, compliance target, or PEEP level. 8

40.7 Recruitment, Blood Gases, and Left Atrial Pressure Modify the Response

PEEP can reduce pulmonary vascular load when recruitment relieves low-volume vascular narrowing and improves oxygenation in previously hypoxic regions. Better alveolar oxygenation can reduce local hypoxic vasoconstriction. However, oxygen distribution remains heterogeneous: a ventilator’s oxygen setting does not measure the oxygen tension in every alveolus, and airway pressure does not reveal alveolar oxygen tension.

Overdistension can produce the opposite response by compressing alveolar vessels and increasing high ventilation–perfusion regions. If effective alveolar ventilation falls, PaCO₂ can rise. Hypercapnia and accompanying acidemia can further increase pulmonary vascular tone. The balance depends on the gas-exchange change, the vascular substrate, and the mechanical conditions rather than on the PEEP number alone.

Mekontso Dessap and colleagues studied patients with severe ARDS while increasing PEEP at a fixed plateau pressure, which required a smaller tidal volume. Recruitment and oxygenation improved, but hypercapnia, acidemia, RV dilatation, LV deformation, and reduced cardiac index developed. Because several variables changed together, the study does not isolate the effect of PEEP from the effects of altered ventilation and blood gases. It directly illustrates why useful recruitment can coexist with circulatory intolerance. 9

Pulmonary vascular pressure itself changes the mechanical response. Increased flow can recruit and distend vascular pathways. Elevated left atrial pressure can keep some vessels open against surrounding pressure, while increasing the downstream load and favoring fluid filtration. Reducing left atrial pressure may relieve congestion but can also change regional zone conditions.

This makes an isolated oxygenation or resistance response difficult to generalize. The response at one cardiac output, PAWP, blood-gas state, and body position may differ when those conditions change. Assessing PEEP therefore includes ventilation and acid–base effects, not merely the arterial oxygen value.

40.8 RV Tolerance Depends on Pulsatile Load and Ventricular Interaction

The RV ejects into a pulsatile circulation. Pulmonary arterial compliance determines how much pressure rises as a stroke volume enters the arterial tree. Wave reflections and the timing of pressure relative to ejection add load that a mean PVR calculation cannot fully describe. A circulation with reduced compliance can require greater pulsatile work at the same mean resistance.

Tedford and colleagues analyzed invasive human hemodynamic data and showed that elevated wedge pressure altered the resistance–compliance relationship, increasing pulsatile loading relative to resistance. Their findings support considering downstream pressure and compliance when interpreting RV load; they do not provide a PEEP-specific correction formula. 10

When the RV cannot maintain ejection against the new load, end-systolic volume rises and the chamber can dilate. A larger radius and higher pressure increase myocardial wall stress, although the RV’s complex geometry prevents a simple bedside wall-stress calculation. Increased demand can then coincide with impaired coronary supply if systemic arterial pressure falls while RV cavity pressure and surrounding pressure rise. Coronary perfusion depends on arterial pressure relative to downstream and intramyocardial pressures across the cardiac cycle, not on one universal pressure difference.

Experiments with controlled pressure around an isolated canine heart demonstrated direct impairment of coronary flow. Their extreme pressure range should not be treated as a clinical PEEP threshold, but the findings reinforce that surrounding pressure can affect supply as well as cardiac work. 11

RV enlargement also changes LV filling through the shared septum and pericardial space. Leftward septal displacement can reduce LV filling even when a measured filling pressure rises. Jardin and colleagues demonstrated altered septal geometry and reduced output during PEEP in patients with ARDS. The study supports ventricular interaction as one mechanism, rather than establishing it as the cause of every PEEP-related output fall. 12

40.9 CVP and PAWP Remain Measurements Requiring a Mechanical Explanation

CVP approximates right atrial intravascular pressure when the catheter and waveform are appropriate. Under PEEP, a rise may reflect greater surrounding pressure, a change in chamber distension, impaired RV emptying, altered venous return, or several processes together. The numerical rise cannot distinguish those mechanisms.

PAWP estimates pressure transmitted through an occluded pulmonary arterial pathway toward the pulmonary veins and left atrium. A valid tracing and appropriate vascular communication are essential. If alveolar pressure interrupts that fluid connection, the measurement can become influenced by alveolar conditions rather than faithfully representing left atrial pressure.

High PEEP does not automatically invalidate every wedge measurement. Teboul and colleagues compared simultaneous occlusion pressure and LV end-diastolic pressure in selected patients with severe ARDS and found close correspondence under their study conditions despite substantial PEEP. Catheter location, pathology, and pressure transmission therefore matter more than declaring a fixed PEEP level beyond which PAWP becomes meaningless. 13

Even accurate intravascular or intracavitary pressure is not identical to pressure across the chamber wall or to chamber volume. An external-pressure rise can increase measured PAWP while reducing LV filling. Conversely, ventricular interaction can change the pressure–volume relationship. These possibilities explain why a pressure change must be paired with flow, chamber appearance, and the clinical state.

Compare measurements at a defined respiratory phase and with a consistent anatomical reference. End-expiration improves comparability but does not remove intrinsic PEEP or external pressure. Active expiration and strong inspiratory efforts can undermine an apparently simple end-expiratory reading.

Esophageal estimates can help explain pressure transmission, with the technical and regional limitations developed in Chapter 23. They should not be treated as direct pericardial pressure or subtracted automatically from every vascular reading. A high CVP after PEEP is neither proof of volume excess nor an instruction to give more volume; it identifies a pressure state whose cause needs clarification.

40.10 Better Oxygenation Can Coexist With Lower Oxygen Delivery

Recruitment can improve arterial oxygenation by reducing shunt. PEEP can also redistribute pulmonary blood flow, and reduced cardiac output can change mixed venous oxygen content. The arterial oxygen response therefore reflects interacting gas-exchange and circulatory effects rather than recruitment alone.

Systemic oxygen delivery depends on arterial oxygen content multiplied by cardiac output. Consider an illustrative patient whose measured arterial content improves from 12 to 13 mL O₂/dL after a PEEP change. At baseline, output is 5 L/min. Because one liter contains ten deciliters, this carries 50 dL/min of blood. Delivery is therefore 12 × 50 = 600 mL O₂/min.

If output falls to 4 L/min, blood flow becomes 40 dL/min. Despite the higher content, delivery is now 13 × 40 = 520 mL O₂/min. This is an 80 mL O₂/min decrease. The example demonstrates a transport tradeoff; it does not establish that this particular delivery is inadequate, because metabolic demand and regional distribution have not been specified.

Likewise, reduced output does not by itself prove that recruitment was useless. Maintaining aeration may reduce injurious opening and closing or permit other beneficial changes. The question is whether the complete ventilatory and circulatory state remains tolerable and appropriate, judged alongside outcome evidence for the strategy.

Useful paired observations include total PEEP, plateau pressure, tidal volume, blood gases, output or stroke-volume estimates, systemic pressure, and RV size and function. Peripheral perfusion, organ function, and venous congestion provide information about consequences. All measurements require their own technical checks and can change at different speeds.

An improvement in saturation, compliance, or PaO₂/FiO₂ cannot independently establish a survival benefit or certify circulatory tolerance. Conversely, preserving output while allowing substantial derecruitment may worsen lung protection. PEEP assessment requires the combined physiological response.

40.11 Trials Distinguish Higher Maintained PEEP From Recruitment Bundles

PEEP trials evaluate strategies in selected populations. They do not compare an identical increment in every lung or establish which mechanism explains an individual patient’s response. Chapter 26 develops their respiratory context; their circulatory implications depend on preserving the intervention distinctions.

ALVEOLI compared higher and lower PEEP–oxygen strategies during low-tidal-volume ventilation. Overall outcomes, including hospital mortality, were not significantly different. 14 LOVS combined higher PEEP with recruitment maneuvers and other protocol differences. It reduced some hypoxemia-related outcomes without demonstrating a significant primary hospital-mortality benefit. 15 EXPRESS increased PEEP toward a specified plateau-pressure range, compared with a minimal-distension strategy. The primary 28-day mortality comparison was not significant, although some secondary recovery outcomes favored the higher-PEEP strategy. 16

An individual-patient analysis of these trials found heterogeneity according to baseline oxygenation severity, with a favorable higher-PEEP signal among patients meeting the analysis’s ARDS oxygenation criterion. This supports attention to population selection. Oxygenation severity nevertheless does not directly measure recruitability, vascular tolerance, or RV reserve. 17

ART tested a different, intensive combination: recruitment maneuvers followed by compliance-based PEEP titration. Mortality at 28 days increased from 49.3% in the low-PEEP control group to 55.3% in the intervention group, and barotrauma increased. The trial establishes harm from the strategy tested; it does not isolate maintained PEEP from recruitment maneuvers or prove that every PEEP increase is harmful. 18

The 2026 Surviving Sepsis Campaign conditionally suggests higher rather than lower PEEP for adults with sepsis and moderate–severe ARDS, with moderate-certainty evidence. It strongly recommends against an incremental PEEP titration strategy in that population, also with moderate certainty. 19 The distinction between maintained-pressure strategies and the recruitment/titration protocols in the evidence base is essential. These recommendations are not an instruction to keep increasing pressure until oxygenation or compliance reaches an apparent optimum.

Hemodynamic observations help explain benefit and intolerance within these frameworks. They do not override trial evidence by turning a favorable short-term oxygen response into proof that a harmful protocol has become beneficial.

40.12 Interpret a PEEP Change as a Linked Lung–Circulation Experiment

Consider an illustrative patient with ARDS whose PEEP is increased for persistent hypoxemia. Oxygenation improves and driving pressure decreases at the same tidal volume. However, stroke volume falls, CVP rises, and echocardiography shows greater RV dilatation with septal flattening. The pulmonary improvement is real, but the entire response includes a circulatory cost requiring explanation.

First establish whether the comparison is valid. Confirm total rather than only applied PEEP, passive or active breathing conditions, airway waveforms, pressure references, and the reliability of the flow estimate. Check whether posture, rhythm, vasoactive support, tidal volume, or blood gases changed. A nominally isolated PEEP change can alter several physiological variables indirectly.

Then locate the likely limitation. A fall in venous return may reflect a changed filling-pressure gradient or vascular compression. RV dilatation with reduced ejection raises concern about increased outflow load or inadequate RV reserve. New hypercapnia and acidemia can add vascular load. A rise in measured PAWP can reflect external pressure or altered cardiac interaction rather than greater LV volume.

The next adjustment should address that explanation while considering the respiratory consequences. Reducing excessive distension may improve RV ejection but can allow derecruitment. Altering ventilation or position can change gas exchange and loading together. Additional fluid is not a default response to every output fall: an overloaded, dilating RV may become less effective when further distended.

Reassess after the new state develops and continue watching organ perfusion and congestion. Early pressure transmission, later recruitment or derecruitment, and evolving circulatory compensation need not follow identical timescales. Recovery of lung disease, a posture change, or renewed patient effort can change tolerance again.

The aim is a defensible balance between useful aeration, acceptable regional distension, sustained RV function, and adequate tissue perfusion. No one airway pressure, filling pressure, oxygen value, or compliance measurement can independently define that balance.

References

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18. 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

19. 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.