Let's start with a little multiple choice. Which mechanism(s) could contribute to hypoxemia in this patient?

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The answer is ALL of the above!

But why? To answer, we need to understand what PEEP is and what effects it has on the lung.
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Positive end expiratory pressure (PEEP) is the pressure above atmospheric that is applied in between breaths while on a mechanical ventilator.

PEEP is beneficial for two reasons:
1️⃣ PEEP recruits collapsed lung (see video)
2️⃣ greater alveolar pressure drives more O2 into the blood (Henry's law)

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As an aside, it's worth noting that the benefits of PEEP in ARDS were discovered *accidentally*.

In 1967, two doctors caring for a patient on a ventilatory spotted a knob labeled "expiratory retard" and - not knowing what it did - decided to give it a try. It worked!

Nowadays we call that knob PEEP and it's an indispensable part of mechanical ventilation.

https://pubmed.ncbi.nlm.nih.gov/28731363/

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Ok so we understand why PEEP can help, but why can PEEP be *harmful*?

We need to understand the relationship between lung volumes & pulmonary blood flow.

Let's take a closer look at the alveoli. With the help of an electron microscope we can see that alveoli are surrounded by a dense interconnected network of blood vessels.

(btw, if you were wondering, they obtain these amazing images by injecting the vessels with a polymer, dissolving the remaining tissue, then taking SEM micrographs)
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There's a dynamic relationship between alveoli inflation & blood flow.

As the alveoli become more inflated, blood flow through these dense intra-alveolar vessels decreases. This increases the pulmonary vascular resistance (PVR).

PVR is lowest at Functional residual capacity (where normal tidal breathing occurs). PVR increases with both lower or higher lung volumes.
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Adding too much PEEP can overdistend the alveoli and decrease blood flow through the intra-alveolar vessels responsible for gas exchange.

It also increases blood flow through the extra-alveolar blood vessels, which do not participate in gas exchange.

This causes intra-pulmonary shunt and causes hypoxemia!
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Another factor to consider is that the effects of PEEP aren't uniform, especially if different areas have different compliance.

Areas of the lung that are affected by pneumonia may not be recruitable, but normal areas may become overdistended with too much PEEP. This too can worsen intra-pulmonary shunt & cause hypoxemia.
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Now that we understand how PEEP effects the lungs, we also need to consider how PEEP effects the heart.

We've already talked about how larger volumes can increase PVR. This increases RV afterload & right sided pressures.

For the 25% of the population with a PFO, this rise in right sided pressures may cause R-->L shunt, causing hypoxemia due to an intra-cardiac shunt.
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Finally, we need to consider the effects of PEEP on cardiac output.

Applying PEEP decreases venous return because of increased intrathoracic pressure (which reduces venous filling).

Depending on the patients volume status a decrease in preload *usually* decreases cardiac output.

(btw check out the great explanation at https://derangedphysiology.com/main/home )

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1414045/#:~:text=Except%20from%20the%20failing%20ventricle,positive%2Dpressure%20ventilation%20were%20measured
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Decreasing cardiac output has many physiologic effects (hypotension, reflex tachycardia, decreased UOP, etc). But why does low CO worsen hypoxemia?

Recall that low CO drops the mixed venous O2 sat due to stagnant blood flow. If your SvO2 drops low enough it will worsen hypoxemia. This is the SIXTH cause of hypoxemia (which is often overlooked).

See my ICU OnePager on hypoxemia for more on this.
https://onepagericu.com/hypoxia

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