TEMP

As late as the 1990s it was common practive to ventilate with TVs of 10-15 mL/kg actual body weight

• this changed in 2000 with publication of the ARDSnet ARMA study, which demonstrated a TV of 6 vs 12 mL/kg predicted body weight decreased mortality to 31.0% from 39.8% (p=0.007, NNT 11) and increased ventilator-free days to 12 from 10 (p=0.007)

• the protocol used low tidal volumes to minimize volutrauma & higher PEEPs to prevent de-recruitment of alveoli

VILI refers to acute injury of the small airways & lung parenchyma caused by, exacerbated by, or simply associated with mechanical ventilation; there is specific terminology for the precise mechanism of injury:

• volutrauma: alveolar overdistention due to elevated transalveolar pressure; the term "volu" is used because studies reference this injury pattern in the context of high tidal volume ventilation

• barotrauma: alveolar rupture due to elevated transalveolar pressure, leading to PTX, pneumomediastinum, pneumoperitoneum, & subcutaneous emphysema

• atelectrauma: shear force generated by cyclic alveolar expansion (during inspiration) & collapse (during exhalation) that distends & injures adjacent alveoli & airways 

• biotrauma: volutrauma- and/or atelectrauma-related release of inflammatory mediators which independently cause further lung injury, which may be related to subsequent development of pulmonary fibrosis

compliance is the ratio of between the change in volume to the change in pressure

• C = ΔP / ΔV

conceptually, compliance refers stiffness vs floppiness

• low compliance: a higher pressure change produces a smaller volume change (i.e., a stiff lung)

• high compliance: a lower pressure changes produces a larger volume change (i.e., a floppy lung)

total compliance of the respiratory system (compRS) comes from both chest wall compliance (compCW) & the lungs (compL), which are considered together in a parallel circuit

• 1 / compRS = 1 / compCW + 1 / compL

• therefore, any disease process that affects the lungs (i.e., PNA, atelectasis, pulmonary fibrosis, pulmonary edema, PTX) or chest wall (subcutaneous edema, circumferential burn, elevated intra-abdominal pressure) will affect respiratory system compliance

The major risk factor for VILI is volutrauma

ARDSNet ARMA showed that low TVs based on predicted body weight (PBW) produce a clinically significant mortality reduction

the appropriate TV depends on PBW, where the underlying assumption is that lungs do not change in size despite the patient's adiposity (MDCalc)

• males: PBW [kg] = 0.91 × (height [cm] − 152.4) + 50

• females: PBW [kg] = 0.91 × (height [cm] − 152.4) + 45.5

in general, the initial TV should be 6-8 mL/kg PBW

if the patient has ARDS, a TV of 4-6 mL/kg PBW is more appropriate

if the patient has obstructive lung disease, a TV of 7-8 is ideal to prevent air trapping

exceeding a TV of 8 mL/kg PBW has been shown to cause VILI

ARDS is a heterogenous disease (pockets of healthy alveoli & diseased alveoli occupying the same lobes & segments)

as ARDS worsens, fewer healthy alveoli remain to exchange gas

therefore, in ARDS, the reduction in compliance is not like that of pulmonary fibrosis; rather, it is because the functional lungs are much smaller

this healthy lung tissue is what is used during mechanical ventilation & injuring healthy tissue will only worsen things

PBW, unfortunately, does not predict the size of the "baby lung"

in other words, low TVs are not the whole story for LPV

Stress applied to the lung refers to the trans-pulmonary pressure that alveoli feel at end-inspiration

• Stress is inferred by the driving pressure, calculated by gradient between PPlat & PEEP

Strain is related to the volume change from FRC to the volume at end-inspiration

• Strain is conceptually lung "unfolding" where alveoli are not truly balloons and do not inflate uniformly

• Strain is literally the force placed on elastic collagen fibers during the volume changes, and it is inferred by the ratio of TV to functional residual capacity (FRC)

  • • FRC is the lung volume at end-expiration (inward pull of the lungs is balanced by outward pull of chest wall)

      • at FRC, healthy alveoli remain open & participate in gas exchange

      • most disease states that cause RF are restrictive, thereby reducing FRC

      • normal FRC is about 35 mL/kg PBW

    • we can allow TV up to the total lung capacity (TLC)

      • healthy TLC is about 80 mL/kg PBW

• If we allow the TV up to a healthy TLC of 80 mL/kg PBW, from an FRC of 35 mL/kg PBW, then

  • a healthy TV would be 45 mL/kg PBW

  • normal strain is therefore TV / FRC = 45 / 35 = 1.3

Stress & strain are related as follows: stress = k × strain

• k is lung elastance, which in both healthy & diseased human lung is known to be 13.5 cm H2O / L

If we substitute driving pressure for stress, 1.3 for strain, and 13.5 for k, then we get

• driving pressure = 13.5 x 1.3 = 17 cm H2O

no prospective clinical trials have proven that using a driving pressure-governed ventilation strategy reduces mortality

• but the theory is that a driving pressure < 17 balances stress & strain

• a retrospective review of ARDSNet data demonstrated that a driving pressure > 15 cm H2O was associated with excess mortality

in disease states, open alveoli are often adjacent to flooded and/or collapsed alveoli

walls of the collapsed alveoli tug on those of healthy alveoli

when stress is applied, the effect on the healthy alveoli is therefore multiplied

stress can theoretically be multiplied as much as 4.64 times when healthy alveoli are surrounded by diseased alveoli

• i.e., a PPlat of 30 could generate a trans-pulmonary pressure of 140

• in practice, the multiplier seems to be closer to 2.0

• multipliers are most pronounced in areas of atelectasis

PEEP recruits collapsed lung units & prevents collapsing at end-expiration

• adequate PEEP spreads out stress among more lung tissue

• this generally requires 5-15 of PEEP

• if PEEP is too low you won't reduce atelectrauma

• if PEEP is too high, alveoli septae can rupture & cause hemorrhagic pulmonary edema

• high PEEP also can compromise RV function

Prone positioning also moderates stress

• much of lung collapse in ARDS is from gravitational compression

  • periodically changing from supine to prone changes the gravitational vector, thereby helping to open collapsed lung units

• proning also "homogenizes" intra-thoracic pressure among lung units

  • when supine, the anterior chest wall moves forward easily during respiration

    • the ventral lung units therefore get the bulk of ventilation

    • the dorsal lung units tend to remain collapsed

  • when placed in the prone position, anterior chest wall excursion is limited

    • since the posterior wall is constrained by the ribs, spine, & scapulae, the breath delivery is spread more evenly throughout the lungs

Airway pressure release ventilation (APRV) can also mitigate stress

• lungs are not uniformly elastic like a rubber band or balloon

• lungs are viscoelastic, akin to silly putty or Play-Doh, where a change in pressure will inflate the lungs, but it takes more time for the alveoli to unfold into a fully inflated form

  • likewise, a sudden drop in airway pressure will lead to alveolar collapse, but over time

• APRV capitalizes on this principle by using a prolonged high pressure w/periodic releases to open up & stabilize the lung

• release times are short enough to permit expiratory gas flow while not allowing lung units to collapse

• these benefits of APRV are not well studied, but in theory are consistent with LPV

FiO2 > 60% was described in the 1970s as associated w/lung injury

• recall, this this was an era when low (or no) PEEP and TVs of 10-15 mL/kg ABW

in neonates, paO2 > 150 is associated w/retinal hyperplasia & blindness

cerebral & cardiac vasoconstriction have also been described w/hyperoxemia

hyperoxemia is thought to exacerbate normal ROS formation, exceeds natural antioxidant mechanisms, thereby contributing to inflammation

paO2 > 300 is associated w/higher risk of in-hospital mortality in patients w/cardiac arrest & hypoxic-ischemic encephalopathy

routine administration of 8 L/min O2 to patients with STEMI is associated w/a larger infarct size & a higher rate of recurrent MI

targeting a paO2 of 70-100% & SpO2 94-98% reduces mortality compared to goal paO2 up to 150 & goal SpO2 97-100%

targeting goal SpO2 91-96% has no effect on mortality or LOS when compared w/a goal of 91-100%