Improvement of the V/Q match is because dorsal part of lungs receives even after pronation majority of blood supply, this is independent of the gravitation. Moreover, dorsal parts of the lungs have now better chance to be recruited and effectively ventilated due to several mechanisms, one of them is reduction of the ventral-dorsal transpulmonary gradient (difference between alveolar and pleural pressure) with more homogenous ventilation. Heart is now lying on the sternum and is no longer compressing lungs so dorsal parts of lungs are easier to be recruited, diaphragm is displaced caudally and gives lung more space as well. As the dorsal parts of lungs are anatomically bigger, recruitment of these parts will improve overall oxygenation of the blood.Secretion clearance is slightly better in the prone position, which makes a minor contribution to overall oxygenation improvement.

Pplat is the pressure measured under static conditions when there is no flow present. This is measured by an inspiratory hold maneuver. This value is dependent solely on the compliance of the respiratory system and corresponds with intra-alveolar pressure.Pneumothorax is characterized by a decrease in the compliance of the respiratory system; the lung does not have enough space to expand. Similar situations include restrictive lung disease, a rigid chest wall, obesity, increased intra-abdominal pressure, etc.All other options would signify an increase in airway resistance where PIP would be increased dramatically, as PIP is measured when airflow is present. The PIP value is dependent on both compliance and airway resistance. A “shark fin” shaped capnography curve and persistent flow at the end of expiration are classically seen in bronchospasm, for example.

Driving pressure is calculated as plateau pressure minus PEEP.To determine plateau pressure during VCV (volume-controlled ventilation), an inspiratory hold maneuver for at least 3 seconds needs to be performed. This will provide a no-flow state, allowing for the measurement of plateau pressure.If PCV (pressure-controlled ventilation) is used, plateau pressure is determined at the end of inspiration.Driving pressure is the pressure that distends the lungs from the end-expiratory lung volume (maintained by PEEP) and directly affects tidal volume. The final tidal volume is influenced by multiple factors, such as lung compliance, chest wall compliance, airway resistance, and the duration of inspiration.Driving pressure is becoming important in the concepts of protective lung ventilation, as limiting driving pressure seems beneficial and can prevent ventilator-associated lung injury. A commonly cited rough guide is to keep driving pressure under 15 cm H2O.

) Stress and strain are newer concepts describing mechanisms of lung injury. The term "stress" refers to the mechanical load applied to the lungs and correlates with transpulmonary pressure. Transpulmonary pressure can be calculated as the difference between intra-alveolar and pleural pressure. This new concept highlights the importance of considering not only absolute pressures, such as Pplat, but also pleural pressure.

Transpulmonary pressure can be measured at end-inspiration (Pplat minus esophageal pressure at the end of inspiration) or at end-expiration (PEEP minus esophageal pressure at the end of expiration).

Pleural pressure is commonly measured by esophageal manometry in clinical practice. This semi-invasive technique requires a special balloon connected to a transducer, positioned in the lower third of the esophagus.

The use of transpulmonary pressure in ARDS or obese patients to guide PEEP, with the aim of ensuring a positive end-expiratory transpulmonary pressure, helps to avoid end-expiratory lung collapse. This leads to improved oxygenation and respiratory system compliance.

Real lungs are non-homogenous and different parts of lungs carries different physiological and physical properties, even for healthy lungs. That means that strain is heterogenous throughout the lungs.

Stress and strain are newer concepts describing mechanisms of lung injury. In physics, for example, linear strain is the change in length divided by the original length.Strain in the lungs is the change in lung volume during respiration (Vt) divided by the initial volume (FRC or functional residual capacity).Global volumetric lung strain is measured as Vt/FRC. This indicates that higher Vt increases lung strain. Secondly, FRC plays an important role in this concept. In healthy lungs, FRC is close to 2.5 liters; with a Vt of 500 ml, the strain would be 20%. But imagine a situation where FRC is dramatically decreased, such as in ARDS, where FRC can be around 500 ml. With the same Vt of 500 ml, the strain would now be 100%.It can be understood that the lungs have an elastic capacity to distend to some extent, but if this capacity is reached and distention continues, lung structures begin to be damaged. Imagine pushing 500 ml of air into whole healthy lungs and the same volume into just one lobe. This explains the strain concept, if you over-distend a metal spring, it won’t return to its original shape, and the capacity of this spring is based on its initial length (FRC in terms of lung strain).

The term "stress" refers to the mechanical load applied to the lungs and correlates with transpulmonary pressure. Transpulmonary pressure can be calculated as the difference between intra-alveolar and pleural pressure. This new concept highlights the importance of considering not only absolute pressures, such as Pplat, but also pleural pressure.

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Pplat is the pressure measured under static conditions when there is no flow present. This is measured by an inspiratory hold maneuver, ideally for more than 3 seconds to allow enough time for equilibration of pressures. Pplat correlates with intra-alveolar pressure during inspiration.Controlling Pplat was generally used to limit Ventilator-Induced Lung Injury (VILI), but newer concepts like stress, strain, and driving pressure seem more relevant.

The onset for diagnosis is limited to 7 days after a known insult. Data suggest that most cases of ARDS develop within 72 hours

Increased non-ventilated lung tissue leads to a decrease in lung compliance (an increase in elastance). In other words, some parts of the lungs are collapsed and almost impossible to recruit, while other parts of the lungs can be recruited with proper maneuvers, and PEEP will keep these parts recruited. Additionally, there can be a zone that is normally functioning and could prone to hyperinflation. Considering all the previously mentioned factors, FRC is significantly decreased, and the effective functioning lung volume is reduced, clinically referred to as 'baby lungs.'

ARDS is a syndrome that encompasses a spectrum of conditions with different etiologies that have similar pathophysiological and clinical presentations. These features include increased permeability of the alveolar-capillary membrane, leading to inflammatory edema and intra-alveolar fluid accumulation with subsequent hyaline membrane formation. A histologic finding commonly seen in ARDS patients is known as 'diffuse alveolar damage. '

As mentioned previously FRC would be decreased.

ARDS can, to some extent, mimic cardiogenic pulmonary edema. These two conditions can present simultaneously. For ARDS to be diagnosed, pulmonary symptoms like hypoxemia and bilateral opacifications on X-ray cannot be fully explained by cardiogenic failure. There is no need for formal cardiac catheterization or echocardiography to diagnose ARDS, and the PCWP cutoff is no longer used, as some increase in cardiac filling pressures can coexist.

In the Berlin criteria, a PEEP requirement of ≥ 5 cm H2O by PPV or NIV (CPAP) is necessary for diagnosis. Newer discussions suggest the ability to diagnose ARDS even with just High-Flow Nasal Cannula (HFNC), but this is not part of the Berlin criteria.

Radiological findings such as bilateral opacities are typical, but different findings can be seen as well. Chest X-ray or CT can be used interchangeably. Opacities should not be fully explained by effusions, lobar or lung atelectasis, or nodules or masses. Again, newer discussions allow for the use of lung ultrasound, but this is not part of the Berlin criteria.

The onset for diagnosis is limited to 7 days after a known insult. Data suggest that most cases of ARDS develop within 72 hours.

Multiple trauma is a well-known risk factor for the development of ARDS. In our differential diagnosis, we should consider fat embolism syndrome, which can cause an ARDS-like picture. TRALI typically develops within 6 hours after the administration of plasma-rich blood products like FFP. Lung contusions are usually localized to the area of impact and can lead to an inflammatory response and an ARDS-like picture as well.

Sepsis is a common extrapulmonary cause of ARDS. Typical radiological findings in ARDS include pulmonary opacification with an anteroposterior gradient and transition to dense consolidation in dependent regions. Non-specific ground-glass opacification, which represents decreased aerated lung volumes, and hyperexpanded lungs in non-dependent regions can also commonly be seen.

Pancreatitis is another common extrapulmonary cause of ARDS. Consolidated (non-aerated) lung tissue leads to a decrease in lung compliance. These parts of the lungs are collapsed and almost impossible to recruit, while other parts of the lungs can be recruited with proper maneuvers. Additionally, there can be a zone that is normally functioning and a zone that is prone to hyperinflation. Considering all the mentioned factors, FRC is significantly decreased, and the effective functioning lung volume is reduced, clinically referred to as 'baby lungs.'

ARDS develops within days, and the cutoff for diagnosis is 1 week since the insult.

In ARDS, effective lung volume decreases due to intra-alveolar fluid accumulation and surfactant dysfunction, leading to diffuse consolidation and compressive atelectasis, which are dominant in dependent regions. These smaller functional lungs are referred to as 'baby lungs,' and to prevent ventilator-induced lung injury (VILI), lung-protective ventilation strategies are employed. These strategies include permissive hypercapnia, which means tolerating higher PaCO2 values as long as pH is > 7.2. This approach allows for the use of lower tidal volumes, lower driving pressure, and avoidance of VILI.

Prone positioning is one of the rescue maneuvers to improve oxygenation by recruiting the dorsal parts of the lungs (now non-dependent), thereby increasing the number of ventilated alveoli. Studies have shown decreased mortality with prone positioning. Other benefits include decreasing the risk of VILI and reducing right ventricular strain.

Theoretical benefits of neuromuscular blocking agents (NMBAs) include reducing the work of breathing and improving patient-ventilator synchronization. On the other hand, neuromuscular weakness and the need for deep sedation are important drawbacks of NMBA use. Modern ICU care prioritizes lighter sedation and faster return to spontaneous respiration. Recent trials have shown no mortality benefit with routine use of NMBA infusion in the first 48 hours compared to standard care. However, this does not apply to specific situations such as significant patient-ventilator asynchrony, where the use of NMBAs may be necessary.

Lung-protective ventilation with a tidal volume (Vt) of 4 to 8 mL/kg is calculated using predicted body weight. Predicted body weight depends on the gender and height of the patient. The use of lung-protective ventilation has shown mortality benefits in multiple studies. Maintaining plateau pressure (Pplat) < 30 cm H2O is also a key component of lung-protective ventilation.Note: PBW (predicted body weight) and IBW (ideal body weight) are sometimes used interchangeably, as these weights are practically the same.

ARDS causes heterogeneous lung injury with reduction of regions that function normally and are prone to overdistention, consolidated regions due to intra-alveolar fluid accumulation and surfactant dysfunction, and atelectatic regions mostly in dependent zones. The existence of these heterogeneous areas is an important predisposition for VILI. The use of PEEP can homogenize these regions, prevent repeated recruitment and collapse, and improve oxygenation. However, too much PEEP can lead to overdistention, hyperinflation lung injury, and hemodynamic collapse.

Controlling Pplat is recommended to limit Ventilator-Induced Lung Injury (VILI), generally keeping it under 30 cm H2O. Newer concepts such as stress, strain, and driving pressure also seem relevant.

Prone positioning improves homogenization of the lungs and decreases the risk of VILI. By recruiting the dorsal parts of the lungs (now non-dependent), the prone position increases alveolar recruitment, leading to better oxygenation and less right ventricular strain. Moreover, studies have shown decreased mortality with prone positioning.

Patients with high respiratory drive generate very negative pleural pressure. By adding positive pressure with NIV (mainly BiPAP), we can generate high transpulmonary pressure in this subgroup of patients. Transpulmonary pressure is the difference between intra-alveolar pressure and pleural pressure and is related to the concept of lung stress. This kind of lung injury, partially caused by the patient's effort, is referred as Patient Self-Inflicted Lung Injury (P-SILI).

In the right (inflamed/injured) lung, there is a decrease in intralveolar oxygen pressure because the alveoli are filled with fluids. If these alveoli are perfused, it leads to the creation of a V/Q mismatch and, if severe enough, a shunt.The physiological counter mechanism is hypoxic pulmonary vasoconstriction, which causes vasoconstriction in hypoxic alveoli and tries to shift blood flow to better-oxygenated parts of the lung. If the patient is positioned on the left side, blood flow to the healthy left lung is encouraged by gravity. Conversely, if the patient is positioned on the right side, gravity would draw blood flow to the right (fluid-filled, hypoxic) lung and worsen the shunt.

Severe asthma is characterized by high airway resistance due to bronchospasm. This will be reflected by high peak inspiratory pressures (PIP) required to overcome these narrow airways.

Plateau pressure (Pplat) is measured by an inspiratory hold maneuver and would be relatively 'normal'. This value depends on the compliance of the respiratory system and corresponds with intra-alveolar pressure. High airway resistance has no effect on this number. A high Pplat could be a sign of dynamic hyperinflation, which can develop if not enough time is allowed for complete expiration. The solution would be to prolong the expiratory phase.

After initiation of PPV, considering a low respiratory rate (RR) between 8–12 per minute and an I:E ratio of 1:3-4 to allow prolonged expiratory flow, CO2 levels will tend to rise. This permissive hypercarbia is usually tolerated as long as the pH remains above 7.2. On capnography, a characteristic ''shark fin'' shaped curve would indicate bronchospasm.

Asthma is characterized by a prolonged expiratory phase. If the expiratory phase is too short, we can notice the presence of end-expiratory flow, which could lead to dynamic hyperinflation with multiple consequences. Prevention involves eliminating the cause with bronchodilation therapy and allowing enough time for expiration (emptying the lungs) by applying a low respiratory rate (RR) and an I:E ratio of 1:3-1:5.

Patients with acute bronchospasm (increased airway resistance) are challenging to ventilate. First, if possible, we try to avoid intubation and positive pressure ventilation (PPV). If non-invasive techniques fail and PPV is initiated, our goals are to ensure adequate oxygenation and prevent complications due to hyperinflation. Due to the increased airway resistance, prolonging the expiratory phase is necessary to allow complete emptying of the lungs. This can be achieved by using a low respiratory rate and setting the I:E ratio to 1:3 or 1:5.Unwanted consequences of dynamic hyperinflation can include decreased compliance, reduced tidal volume (Vt), and an increase in plateau pressure (Pplat). The cardiovascular system may be affected by decreased preload, which can lead to hypotension or even cardiac arrest.Due to low minute ventilation, an increase in PaCO₂ can be expected. Tolerating elevated PaCO₂ is possible as long as the pH remains above 7.2, a strategy known as permissive hypercapnia.As the acute situation improves, it is possible to cautiously increase the respiratory rate and decrease the I:E ratio, but this should be done with meticulous monitoring to prevent hyperinflation.

PEF is measured as a percentage of the best previously measured value. If no previous physiological value is available for comparison, we use predicted values. Values under 50% are considered severe asthma, and values under 33% are considered life-threatening asthma.

A silent chest in an asthmatic patient can signal very poor air entry and imminent respiratory failure. Other strong warning signs are cyanosis, poor respiratory effort, or signs of exhaustion.

A patient with acute asthma exacerbation tends to hyperventilate, so hypocarbia is expected. A normal value of PaCO2 is a strong indicator of respiratory muscle weakness and impending respiratory failure. Other life-threatening features from blood gases are hypoxemia (PaO2 < 8 kPa) and acidaemia (pH < 7.2).

Altered consciousness can be caused by hypoxemia, hypercapnia, hypotension, or many other reasons. Regardless of the cause, this signals a severe, life-threatening clinical condition with possible airway compromise.

Spontaneously ventilated patients are triggering the ventilator by producing negative pressure inside respiratory system. Existence of PEEPi cause this more difficult and higher negative pressures are required for triggering. Use of PEEPe counterbalance PEEPi and helps with ease triggering of ventilator and subsequently decrease of respiratory work. In case of hight airway resistance, ineffective triggering is common dyssynchrony that leads to ineffective effort of patient.

Increase of airway resistance leads to slower expiratory flow, that means it require prolonged expiratory time for complete emptying of lung volume. If the expiratory phase is too short, like in situations with high respiratory rate, dynamic hyperinflation with multiple consequences will develop. Prolonging expiratory time can be done by applying a low respiratory rate (RR) and an I:E ratio of 1:3-1:5.

Plateau pressure (Pplat) depends on the compliance of the respiratory system and corresponds with intra-alveolar pressure. In dynamic hyperinflation, air become trapped inside the alveoli and lung volumes will progressively increase to the point of overinflation and decreased compliance of respiratory system. This can be seen by increase of Pplat in case of volume-controlled ventilation or as a decrease in tidal volumes in case of pressure-control ventilation.

In passively ventilated patient (with expiratory flow limitation) use of PEEPe does not worsen hyperinflation if is lower than 80% of PEEPi. This means that many authors recommend use of PEEP with the aim of improving oxygenation and homogenisation of lungs. During progressive increase of PEEPe over the limit, increase of Pplat can be noted and PEEPe adjustment should be done.

This ventilatory dyssynchrony is called double triggering. During one patient’s long inspiration, the ventilator delivers two separate inflations. This commonly occurs when a patient's respiratory drive is too high and is met with insufficient pressure support or an overly short inspiratory time. Increasing the pressure support can sometimes improve this problem, as larger volumes could be delivered, meeting the patient's requirements.

In PSV, we manage inspiratory time indirectly using the cycling trigger (or cycling criteria). The cycling criteria define the end of inspiration and the start of expiration, and are sometimes also referred to as the expiratory trigger. These criteria are usually set between 1% and 90% of peak flow. Since the pressure support flow is decremental, setting the cycling threshold to a lower value (e.g., 10%) will prolong the inspiration. Conversely, setting the cycling criteria to a higher value (e.g., 80%) will shorten the inspiratory phase. In cases of double triggering, setting the cycling threshold to a lower value may prolong inspiration and help resolve this dyssynchrony.

In PSV, we manage inspiratory time indirectly using the cycling trigger (or cycling criteria). The cycling criteria define the end of inspiration and the start of expiration, and are sometimes also referred to as the expiratory trigger. These criteria are usually set between 1% and 90% of peak flow. Since the pressure support flow is decremental, setting the cycling threshold to a lower value (e.g., 10%) will prolong the inspiration. Conversely, setting the cycling criteria to a higher value (e.g., 80%) will shorten the inspiratory phase. In cases of double triggering, setting the cycling threshold to a lower value may prolong inspiration and help resolve this dyssynchrony.

The P-ramp or pressure slope correlates with the time it takes to reach maximal inspiratory flow. The P-ramp is measured in milliseconds or as a percentage of the maximal inspiratory flow. By prolonging the time to achieve the desired flow, we can increase the inspiratory time. Conversely, shortening this incremental phase may lead to increased peak pressures, which can result in the premature termination of inspiration when a fixed percentage of the cycling criteria is reached, thereby shortening the inspiratory phase.

Hypoxic pulmonary vasoconstriction (HPV) is a compensatory physiological mechanism that occurs when some alveoli do not have enough oxygen. The blood vessels supplying these hypoxic alveoli constrict, limiting blood flow to these areas. The timing of HPV is believed to be biphasic. The first phase starts within seconds and reaches its peak effect between 5 to 20 minutes. The second phase peaks around 60 to 120 minutes. These phases involve slightly different molecular mechanisms.

HPV is not perfectly efficient, and some residual shunt can remain in the hypoxic parts of the lungs. For example, in a patient with pneumonia with hypoxemia due to V/Q mismatch, not all blood is shifted to the healthy parts of the lungs.

Pulmonary vasoconstriction increases the afterload for the right heart. This is particularly significant in conditions of global hypoxia, such as long-term COPD or obstructive sleep apnea, where prolonged hypoxic events can eventually lead to right heart failure. Acute hypoxia caused by ARDS can lead to acute decompensation of right heart failure through this mechanism.

HPV is augmented by factors such as acidosis and hypercapnia. Conversely, vasodilatory drugs like nitrates or calcium channel blockers can diminish this effect.

Continuous positive airway pressure (CPAP) uses a single pressure level and is commonly used in cases of acute cardiac decompensation. Its effects include decreasing preload and afterload for the heart, thereby aiding in improving cardiac function.Bilevel positive airway pressure (BiPAP) uses two levels of pressure: Inspiratory Positive Airway Pressure (IPAP) during inspiration functions similarly to pressure support, and Expiratory Positive Airway Pressure (EPAP), which helps to keep the airways open. The difference between IPAP and EPAP, along with the patient’s effort, determines the tidal volume. BiPAP improves tidal volumes, reduces the work of breathing, and helps with CO2 elimination. This is particularly useful in COPD exacerbation patients, where the use of BiPAP has shown a mortality benefit.

NIV is associated with PSILI, especially in patients with hypoxemic respiratory failure, that cause high respiratory drive and hight tidal volumes. Consideration for lowering of IPAP/EPAP or possible early intubation may be needed in these patients to avoid unnecessary complications. Continuous positive airway pressure (CPAP) is commonly used in cases of acute cardiac decompensation. When applying positive pressure into the thoracic cavity, the decrease in venous return to the right heart will offload the heart. This effect will also extend to the left heart. Afterload, which correlates with transmural pressure (the difference between systolic pressure inside the ventricle and intrathoracic pressure), will be decreased by applying positive pressure to the airways. Therefore, CPAP decreases afterload and the heart's workload.Both methods allow for the application of high FiO2 to improve blood oxygenation.

Oxygenation primarily depends on the mean pressure (Pmean) in the airways, which is influenced by positive end-expiratory pressure (PEEP) and peak inspiratory pressure (Ppeak). Note that Vt is influenced by Ppeak. With the concept of lung protective ventilation, we avoid increasing Ppeak if the appropriate Vt is already achieved. This is to prevent unnecessary increases in Vt, which could lead to barotrauma or volutrauma.To increase Pmean, adjusting PEEP is a viable option. PEEP prevents the collapse of alveoli at the end of expiration and facilitates their recruitment. Another method to enhance oxygen delivery to the alveoli is by increasing the fraction of inspired oxygen (FiO2).Tidal Volume (Vt) and Respiratory Rate (RR) form minute ventilation, which is responsible for the elimination of carbon dioxide.

When discussing the elimination of carbon dioxide (CO2) from the lungs, the most important determinant is minute ventilation (MV). MV consists of tidal volume (Vt) and respiratory rate (RR). By increasing either Vt or RR, MV will increase, thus enhancing the elimination of CO2 from the lungs.PEEP and FiO2 are main determinants responsible for oxygen delivery to alveoli.

Following guidelines to limit Vt to 6 – 8 ml/kg of IBW (Ideal Body Weight), IBW is calculated through height and is different for males and females. In our patient, IBW is 80 kg, so 6 ml/kg would correspond to 480 ml and 8 ml/kg would be 640 ml of Vt. Anatomical dead space (nose, trachea, bronchi) is estimated to be 2 ml/kg (160 ml in our patient). Note that, intubated patients can have an increase in dead space due to equipment (endotracheal tube, filter, hoses distal to division).Due to low tidal volumes in this situation, air is not efficiently reaching the alveoli, and CO2 retention is occurring. The respiratory rate is high enough, so further increases would not improve CO2 elimination.

Pplat (15 cmH2O) is pressure measured under static conditions, when there is no flow present, this is measured by inspiratory hold maneuverer. This pressure is dependent on compliance of respiratory system. This value corresponds with intra-alveolar pressure. PIP on the other hand is measured when air flow is present and so is dependent on compliance and airway resistance. In situations where PIP is much higher than the Pplat, high airway resistance should be suspected. Practically, several clinical situations can lead to this, such as bronchospasm, partial obstruction of the tube or bronchi by a mucous plug, or kinking of the tube.