Positive End-Expiratory Pressure

Function

Extrinsic PEEP is a ventilator setting that can increase oxygenation. According to Henry’s law, the solubility of a gas in a liquid is directly proportional to the pressure of that gas above the solution’s surface. Thus, increasing PEEP will increase the pressure within the mechanical or noninvasive ventilation system. This external pressure increases oxygen solubility, allowing it to cross the alveolocapillary membrane more easily, increasing the blood’s oxygen content.

PEEP is applied to prevent end-expiratory collapse during passive exhalation. Applying positive pressure inside the airways can open airways that may otherwise collapse, decreasing atelectasis, improving alveolar ventilation, and, in turn, decreasing ventilation/perfusion mismatch [7]. The application of extrinsic PEEP will have a direct impact on oxygenation and an indirect impact on ventilation. The alveolar surface increases by dilating airways, creating more areas for gas exchange and improving ventilation. Nevertheless, extrinsic PEEP should never be used for the sole purpose of increasing ventilation. If carbon dioxide (CO2) is decreased by improving ventilation, pressure support with either bilevel positive airway pressure or invasive ventilation is more appropriate. Selecting and titrating a specific level, especially for patients with ARDS remains challenging despite extensive research on the subject, with current guidelines suggesting higher PEEP strategies in moderate–severe ARDS but emphasizing individualization [[8],[2]]. Furthermore, there is no clear evidence-based guidance regarding initial PEEP settings or how to titrate them early in the course of the illness [[8], [2]]. Many clinicians try a “one-size-fits-all” approach; however, individualized PEEP titration using methods such as driving pressure, compliance, or electrical impedance tomography may offer greater benefit, particularly when tailored to lung injury severity and oxygenation needs [[3], [4]].

Extrinsic PEEP also significantly decreases breathing work [[2], [9]]. In intubated individuals with low lung compliance, breathing can represent up to 30% of total energy expenditure. This increased energy expenditure leads to higher CO2 and lactate production, which can cause acid-base abnormalities. By decreasing the work of breathing, CO2 and lactate production decrease, reducing the need for high minute ventilation (to correct the hypercapnia and acidosis) and thereby decreasing respiratory drive and further decreasing the work of breathing in a positive-feedback loop. Recent physiologic studies confirm that PEEP can also reduce inspiratory effort and mitigate patient self-inflicted lung injury during assisted ventilation [[6]]. Routine application of small amounts of extrinsic PEEP is often called “physiologic PEEP” because it preserves a physiologic end-expiratory volume (functional residual capacity) compared with zero PEEP, which leads to lower lung volumes and alveolar collapse.

Issues of Concern

The use of extrinsic PEEP can also cause several physiologic and clinical complications. Normal respiratory physiology functions as a negative-pressure system. When the diaphragm contracts during inspiration, intrathoracic negative pressure is generated, creating a gradient that draws air into the lungs. This same negative intrathoracic pressure decreases the right atrial (RA) pressure and generates negative pressure on the inferior vena cava, increasing venous return.

The application of extrinsic PEEP changes this physiology. The positive pressure generated by the ventilator or bilevel positive airway pressure is transmitted to the upper airways and ultimately to the alveoli, increasing intrapulmonary and intrathoracic pressure. As a result, RA pressure increases and venous return decreases, reducing preload. The result is a double effect on reduced cardiac output. Lower residual volume means less blood reaches the left ventricle, decreasing cardiac output. The reduced preload positions the heart to work at a less efficient point on the Frank-Starling curve, further reducing cardiac output. The decreased cardiac output decreases mean arterial pressure unless there is a compensatory response of increased systemic vascular resistance. If distributive shock is present (septic, neurogenic, or anaphylactic), systemic vascular resistance is low, worsening the decrease in mean arterial pressure. Extrinsic PEEP would reduce preload and lower the mean arterial pressure further. 

Decreased RA pressure and venous return may benefit patients with cardiogenic pulmonary edema and volume overload. The left ventricle may be overdistended and operating at a less optimal point on the Frank-Starling curve. Decreasing vascular resistance will decrease preload and allow the left ventricle to function more efficiently, thereby increasing cardiac output and improving pulmonary edema. Notably, higher PEEP does not directly improve left ventricular function.[10] Conversely, decreased vascular resistance to the right ventricle reduces pulmonary pressure, reducing pulmonary edema. 

In patients with stroke or subarachnoid hemorrhage, maintaining cerebral perfusion pressure through the effect of extrinsic PEEP on cardiac output and mean arterial pressure is significant. Although PEEP does not directly affect cerebral perfusion pressure, cerebral autoregulation will compensate for changes in mean arterial pressure. If cerebrovascular autoregulation is compromised, a decrease in mean arterial pressure can lead to adverse outcomes.[11]

Extrinsic PEEP can also induce harmful barotrauma, especially in stiff lungs, by increasing plateau pressures. Extrinsic PEEP can also interfere with hemodynamic measurements of right heart catheters. PEEP can affect the geometry and function of the diaphragm by remodeling the muscle fibers due to increased end-expiratory lung volumes.[12] This remodeling reduces muscle length and increases atrophy resulting from the loss of sarcomeres. This longitudinal atrophy is considered an adaptive response of muscles to restore their optimal length for force generation. During ventilator weaning, the rapid release of PEEP upon extubation quickly decreases end-expiratory lung volumes, stretching the adapted, longitudinally atrophied diaphragm fibers to excessive lengths, impairing contraction.[12]  

Patients with chronic obstructive pulmonary disease (COPD) on mechanical ventilation have both intrinsic and extrinsic PEEP, complicating ventilator management. Dynamic hyperinflation and the development of intrinsic PEEP are commonly observed in patients with COPD and acute respiratory failure.[12] Hyperinflation is a progressive (dynamic) because air accumulates in the lungs with each breath due to incomplete exhalation before the next breath. Airflow obstruction secondary to bronchoconstriction, combined with increased minute ventilation (increased respiratory rate and tidal volume) delivered by the ventilator, creates elevated levels of intrinsic PEEP. Patient-ventilator dyssynchrony, increased work of breathing, barotrauma, cardiovascular collapse, and potentially even death can result from high levels of intrinsic PEEP. 

Clinical Significance

Extrinsic PEEP requires an understanding of the type of ventilation (eg, nasal intermittent positive pressure versus invasive mechanical ventilation) and the ventilatory mode (assist-control, synchronized intermittent mandatory ventilation, airway pressure release ventilation). The following principles apply to the use of PEEP in all modes of ventilation:

• Begin with the lowest effective PEEP and increase as tolerated based on the patient’s comfort, oxygenation, and hemodynamic status [[2],[3]]. Current guidelines for ARDS emphasize that initial PEEP should be individualized rather than fixed, using physiologic targets such as driving pressure, compliance, or imaging-based recruitment assessment [[2],[4],[5]].

• Monitor plateau pressures consistently to prevent barotrauma; maintain plateau pressure below 30 cm H2O [[2]].

• Monitor mean arterial pressure while increasing or decreasing PEEP to avoid hemodynamic compromise, as high intrathoracic pressures can reduce venous return and cardiac output [[2],[6]].

• Consider effects on vascular resistance in patients with cardiogenic pulmonary edema. PEEP may reduce left ventricular afterload and improve oxygenation, but excessive levels can impair right ventricular function [[3]]. Premature extubation in this setting can worsen pulmonary edema and lead to reintubation.

• In ARDS, the ARDS Network (ARDSnet) PEEP/FiO2 tables remain a reference, but recent ATS recommendations support higher PEEP strategies in moderate-to-severe ARDS when tolerated, avoiding routine recruitment maneuvers unless indicated. Oxygenation goals include PaO2 55–80 mm Hg or SpO2 88–95%, achieved by titrating PEEP and FiO2 [[2]].

Other Issues

Auto-PEEP or Intrinsic PEEP

Intrinsic, or auto-PEEP, is a complication of mechanically ventilated individuals.[13] Under normal conditions, passive exhalation allows for the complete emptying of air until lung pressure equals atmospheric pressure. When mechanically ventilated, the lungs may not completely deflate, leaving air trapped inside at the end of exhalation. The trapped air generates positive pressure, known as intrinsic or auto-PEEP. With each successive respiratory cycle, air trapping increases. Consequently, the intrathoracic pressure increases, compressing the right atrium and decreasing vascular resistance, causing hypotension, high plateau pressure, and barotrauma. The increased air trapping will also reduce the volume of air inhaled, which increases the work of breathing, oxygen consumption, and carbon dioxide production. This imbalance leads to an increased need for ventilation, a higher respiratory rate, and greater auto-PEEP, perpetuating a vicious cycle.

Factors Leading to Auto-PEEP 

• Airway inflammation and mucus plugs generate dynamic airflow obstruction. Increased expiratory effort increases the pressure around the inflamed or obstructed airways, leading to closure around the plugs and alveolar air trapping.
• High lung compliance, as in COPD, predisposes to dynamic airway collapse during forced exhalation.
• High tidal volume ventilation can result in air trapping if some air is retained when the next breath is delivered.
• High respiratory rates result in shortened expiratory time, increasing air trapping.
• Slow inspiratory flow creates a higher inspiratory-to-expiratory time ratio, resulting in shorter exhalation times and air trapping.

Types of Auto-PEEP

Dynamic hyperinflation with intrinsic expiratory flow obstruction

This is the most common cause of auto-PEEP in patients with COPD because alveolar collapse during expiration leads to air trapping. Low-level extrinsic PEEP can help decrease auto-PEEP by keeping the airways open, encouraging complete exhalation. Airway inflammation and mucus plugs also cause dynamic hyperinflation, although extrinsic PEEP is not as beneficial.

Dynamic hyperinflation without airflow obstruction

This occurs when exhalation time is shortened due to a high respiratory rate, low inspiratory flow, or high tidal volume. Extrinsic PEEP would be detrimental in this case, as it would generate backpressure, preventing airflow from the lungs.

Clinical Clues Suggesting Auto-PEEP

• Incomplete return to baseline on the volume-time curve during mechanical ventilation [14]
• Elevated plateau pressure measurements
• Use of accessory muscles during exhalation (indicates active exhalation by the patient) 
• Decreased blood pressure
• Prolonged expiratory phase
• Sign of respiratory distress

Although there are many reasons for respiratory distress in an intubated individual, the presence of a volume curve that does return to 0 before the next breath is delivered is very highly suggestive of auto-PEEP.

Treating Auto-PEEP

Prompt recognition and intervention are critical to avoid complications such as shock and barotrauma. In the most extreme cases of respiratory distress and associated shock, temporarily disconnecting the patient from the ventilator to allow complete exhalation could be life-saving. In less severe cases, several measures can prevent or treat auto-PEEP:

• Decrease the respiratory rate to allow longer expiratory time and lower the inspiratory-to-expiratory ratio to between 1:3 and 1:5.
• Increasing the inspiratory flow rate to 60 to 100 L/min ensures rapid air delivery during inspiration, allowing longer exhalation.
• Use a square waveform for ventilation flow. While this type of delivery is uncomfortable for the patient, it speeds the inspiration process.
• Reduce tidal volume to decrease the time required for complete exhalation. 
• Reduce respiratory demand by decreasing carbon dioxide and lactate production (control fever and pain, ensure adequate sedation, control anxiety, and treat sepsis).
• Minimize flow obstruction by treating bronchoconstriction with bronchodilators and suctioning mucus plugs. Treat airway inflammation with steroids when indicated.[15]

In cases of dynamic flow obstruction, especially in COPD and alveolar collapse, low-level extrinsic PEEP will maintain airway patency and decrease expiratory resistance.[16]  Extrinsic PEEP will reduce the breathing work for patients with COPD by allowing expiration and decreasing auto-PEEP. However, although asthma is also an obstructive condition, extrinsic PEEP is ineffective due to inflammation-driven obstruction rather than airway collapse.

When extrinsic PEEP is applied to conditions without dynamic airflow obstruction, back pressure prevents air from escaping from the lungs. Notably, extrinsic PEEP initially adds to the auto-PEEP, increasing intrathoracic pressure. Extrinsic PEEP should be maintained below 75% to 85% of the auto-PEEP. The effects are measured by checking the static pressures while increasing extrinsic PEEP in small increments. If the static pressures do not increase, extrinsic PEEP may be beneficial.

Enhancing Healthcare Team Outcomes

All healthcare professionals caring for patients receiving mechanical ventilation should be aware of PEEP's indications and potential adverse effects. One clinician, specifically the respiratory therapist or attending clinician, should adjust the ventilator settings. Nurses who care for patients receiving mechanical ventilation should be aware that high PEEP can lead to barotrauma and a decrease in cardiac output. Protocols should be in place to counter these complications. Patients on mechanical ventilation should be monitored daily to assess the need for changes in ventilator settings.